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Sample records for brown fat cell

  1. Brown Fat Cell Isolation

    OpenAIRE

    sprotocols

    2014-01-01

    Author: C.R. Kahn ### 1.) ISOLATION AND PRIMARY CULTURE OF BROWN FAT PREADIPOCYTES ### Rationale: To prepare primary brown preadipocytes for immortalization: useful for metabolic studies from knockout mice. This consists of the following five protocols. References: Fasshauer, M., J. Klein, K M. Kriauciunas, K. Ueki, M.Benito, and C.R. Kahn. 2001. Essential role of insulin substrate 1 in differentiation of brown adipocytes. *Mol Cell Biol* 21: 319-329. Fasshauer, M....

  2. Intricate Transcriptional Networks of Classical Brown and Beige Fat Cells

    OpenAIRE

    Park, Jun Hong; Hur, Wonhee; Lee, Sean Bong

    2015-01-01

    Brown adipocytes are a specialized cell type that is critical for adaptive thermogenesis, energy homeostasis, and metabolism. In response to cold, both classical brown fat and the newly identified “beige” or “brite” cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1. Once thought to be non-existent in adults, recent studies have discovered active classical brown and beige fat cells in humans, thus reinvigorating interest in br...

  3. Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment

    DEFF Research Database (Denmark)

    Murholm, Maria; Dixen, Karen; Qvortrup, Klaus;

    2009-01-01

    ) and a remarkably higher mitochondrial abundance in brown adipocytes. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a comprehensive characterisation of gene expression linked to mitochondrial DNA replication, transcription and function during white and brown fat cell differentiation in vitro as well as in white...... precursor cells promotes mitochondrial DNA replication, and that silencing of PRDM16 expression during brown fat cell differentiation blunts mitochondrial biogenesis and expression of brown fat cell markers. CONCLUSIONS/SIGNIFICANCE: Using both in vitro and in vivo model systems of white and brown fat cell...

  4. PRDM16 Controls a Brown Fat/Skeletal Muscle Switch

    OpenAIRE

    Seale, Patrick; Bjork, Bryan; Yang, Wenli; Kajimura, Shingo; Kuang, Shihuan; Scime, Anthony; Devarakonda, Srikripa; Chin, Sherry; Conroe, Heather M.; Erdjument-Bromage, Hediye; Tempst, Paul; Rudnicki, Michael A.; Beier, David R; Spiegelman, Bruce M.

    2008-01-01

    Brown fat can increase energy expenditure and protect against obesity through a specialized program of uncoupled respiration. We show here by in vivo fate mapping that brown but not white fat cells arise from precursors that express myf5, a gene previously thought to be expressed only in the myogenic lineage. Notably, the transcriptional regulator, PRDM16 controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat precursors causes a...

  5. Transcriptional Control of Brown Fat Determination by PRDM16

    OpenAIRE

    Seale, Patrick; Kajimura, Shingo; Yang, Wenli; Chin, Sherry; Rohas, Lindsay; Uldry, Marc; Tavernier, Geneviève; Langin, Dominique; Spiegelman, Bruce M.

    2007-01-01

    Brown fat cells are specialized to dissipate energy and can counteract obesity; however, the transcriptional basis of their determination is largely unknown. We show here that the zinc-finger protein PRDM16 is highly enriched in brown fat cells compared to white fat cells. When expressed in white fat cell progenitors, PRDM16 activates a robust brown fat phenotype including induction of PGC-1α, UCP1 and type 2 deiodinase expression, and a remarkable increase in uncoupled respiration. Transgeni...

  6. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

    Full Text Available Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulates health and lifespan.

  7. Morphogenetics in brown, beige and white fat development.

    Science.gov (United States)

    Lin, Jean Z; Farmer, Stephen R

    2016-01-01

    Brown and beige (or brite) fat cells are capable of evoking non-shivering thermogenesis in response to cold and β-adrenergic stimulation. By metabolizing lipids and carbohydrate via uncoupled respiration these cells directly convert energy to heat. The discovery of brown and brown-like adipocytes in adult humans has reinvigorated interest in stimulating brown and beige fat development to combat the obesity epidemic. This review focuses on the role that cytoskeleton dynamics play in the regulation of adipocyte biology, specifically beige and brown fat development and how newly discovered adipogenic morphogens affect these processes. PMID:27386157

  8. Brown fat determination and development from muscle precursor cells by novel action of bone morphogenetic protein 6.

    Directory of Open Access Journals (Sweden)

    Ankur Sharma

    Full Text Available Brown adipose tissue (BAT plays a pivotal role in promoting energy expenditure by the virtue of uncoupling protein-1 (UCP-1 that differentiates BAT from its energy storing white adipose tissue (WAT counterpart. The clinical implication of "classical" BAT (originates from Myf5 positive myoblastic lineage or the "beige" fat (originates through trans-differentiation of WAT activation in improving metabolic parameters is now becoming apparent. However, the inducers and endogenous molecular determinants that govern the lineage commitment and differentiation of classical BAT remain obscure. We report here that in the absence of any forced gene expression, stimulation with bone morphogenetic protein 6 (BMP6 induces brown fat differentiation from skeletal muscle precursor cells of murine and human origins. Through a comprehensive transcriptional profiling approach, we have discovered that two days of BMP6 stimulation in C2C12 myoblast cells is sufficient to induce genes characteristic of brown preadipocytes. This developmental switch is modulated in part by newly identified regulators, Optineurin (Optn and Cyclooxygenase-2 (Cox2. Furthermore, pathway analyses using the Causal Reasoning Engine (CRE identified additional potential causal drivers of this BMP6 induced commitment switch. Subsequent analyses to decipher key pathway that facilitates terminal differentiation of these BMP6 primed cells identified a key role for Insulin Like Growth Factor-1 Receptor (IGF-1R. Collectively these data highlight a therapeutically innovative role for BMP6 by providing a means to enhance the amount of myogenic lineage derived brown fat.

  9. Novel nuances of human brown fat

    DEFF Research Database (Denmark)

    Scheele, Camilla; Larsen, Therese Juhlin; Nielsen, Søren

    2014-01-01

    There is a current debate in the literature on whether human fat derived from the supraclavicular region should be classified as brown, or as the white fat-derived less potent, brite/beige. This commentary addresses whether the existing classification defined in mice is sufficient to describe...... the types of thermogenic adipocytes in humans. We recently published a contradictory mRNA expression signature of human supraclavicular fat defined by an upregulation of the brite marker TBX1 along with the classical brown markers ZIC1 and LHX8, as well as genes indicating brown fat activity including UCP1......, PGC-1α, and PRDM16; and, finally, a downregulation of the white/brite markers HOXC8 and HOXC9. Subcutaneous fat was used as reference material. Another recent study presents a higher expression of ZIC1 and a lower expression of TBX1 in interscapular compared with supraclavicular fat. Here, however...

  10. Transcriptional Regulatory Circuits Controlling Brown Fat Development and Activation

    OpenAIRE

    Seale, Patrick

    2015-01-01

    Brown and beige adipose tissue is specialized for heat production and can be activated to reduce obesity and metabolic dysfunction in animals. Recent studies also have indicated that human brown fat activity levels correlate with leanness. This has revitalized interest in brown fat biology and has driven the discovery of many new regulators of brown fat development and function. This review summarizes recent advances in our understanding of the transcriptional mechanisms that control brown an...

  11. Brown adipogenesis of mouse embryonic stem cells in alginate microstrands

    Science.gov (United States)

    Unser, Andrea Mannarino

    The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders. Employing pluripotent stem cells, with an emphasis on directed differentiation, may overcome many issues currently associated with primary fat cell cultures. However, brown adipocytes are difficult to transplant in vivo due to the instability of fat, in terms of necrosis and neovascularization, once injected. Thus, 3D cell culture systems that have the potential to mimic adipogenic microenvironments are needed, not only to advance brown fat implantation, but also to better understand the role of brown adipocytes in treating obesity. To address this need, we created 3D "Brown-Fat-in-Microstrands" by microfluidic synthesis of alginate hydrogel microstrands that encapsulated cells and directly induced cell differentiation into brown adipocytes, using mouse embryonic stem cells (ESCs) as a model of pluripotent stem cells and brown preadipocytes as a positive control. The effect of hydrogel formation parameters on brown adipogenesis was studied, leading to the establishment of "Brown-Fat-in-Microstrands". Brown adipocyte differentiation within microstrands was confirmed by lipid droplet accumulation, immunocytochemistry and qPCR analysis of gene expression of brown adipocyte marker uncoupling protein 1 (UCP1) in addition to adipocyte marker expression. Compared to a 2D approach, 3D differentiated "Brown-Fat-in-Microstrands" exhibited higher level of brown adipocyte marker expression. The functional analysis of "Brown-Fat-in-Microstrands" was attempted by measuring the mitochondrial activity of ESC-differentiated brown adipocytes in 3D using Seahorse XF24 3 Extracellular Flux Analyzer. The ability to create "Brown-Fat-in-Microstrands" from pluripotent stem cells opens up a new arena to understanding brown adipogenesis and its implications in obesity and metabolic disorders.

  12. Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders

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    So Hun Kim

    2016-02-01

    Full Text Available Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.

  13. Does Brown Fat Protect Against Diseases of Aging?

    OpenAIRE

    Mark P Mattson

    2009-01-01

    The most commonly studied laboratory rodents possess a specialized form of fat called brown adipose tissue (BAT) that generates heat to help maintain body temperature in cold environments. In humans, BAT is abundant during embryonic and early postnatal development, but is absent or present in relatively small amounts in adults where it is located in paracervical and supraclavicular regions. BAT cells can `burn' fatty acid energy substrates to generate heat because they possess large numbers o...

  14. FAT TISSUE DISTRIBUTION BETWEEN SUBCUTANEOUS AND INTERMUSCULAR FAT TISSUE IN SIMMENTAL AND BROWN BULLS

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    S. Žgur

    2007-06-01

    Full Text Available Simmental and Brown bulls from progeny testing station were used to evaluate the effect of breed on fat tissue partition between subcutaneous and intermuscular fat. Bulls (37 Brown and 34 Simmental breed were slaughtered at the same degree of fatness. After slaughter carcasses were first cut into different carcass cuts and further on into lean meat, fat, bones and tendons. Fat was divided up into subcutaneous and intermuscular. Simmental bulls were heavier (average cold carcass side weight from Simmental bulls was 167 kg vs 147 kg from Brown bulls at the same percentage of total carcass fat (10.5 %. Breed has no effect on percentage of subcutaneous and intermuscular fat tissue nor on percentage of subcutaneous fat from total carcass fat. Simmental bulls had higher (p<0.05 subcutaneous fat percentage (subcutaneous fat in the cut / total fat in the cut in brisket and flank and lower (p<0.05 in shoulder than Brown bulls.

  15. FAT TISSUE DISTRIBUTION BETWEEN SUBCUTANEOUS AND INTERMUSCULAR FAT TISSUE IN SIMMENTAL AND BROWN BULLS

    OpenAIRE

    Silvester Žgur; Marko Čepon

    2007-01-01

    Simmental and Brown bulls from progeny testing station were used to evaluate the effect of breed on fat tissue partition between subcutaneous and intermuscular fat. Bulls (37 Brown and 34 Simmental breed) were slaughtered at the same degree of fatness. After slaughter carcasses were first cut into different carcass cuts and further on into lean meat, fat, bones and tendons. Fat was divided up into subcutaneous and intermuscular. Simmental bulls were heavier (average cold carcass side weight ...

  16. Cell biology of fat storage.

    Science.gov (United States)

    Cohen, Paul; Spiegelman, Bruce M

    2016-08-15

    The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development.

  17. Cell biology of fat storage.

    Science.gov (United States)

    Cohen, Paul; Spiegelman, Bruce M

    2016-08-15

    The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development. PMID:27528697

  18. Browning and graying: novel transcriptional regulators of brown and beige fat tissues and aging

    Directory of Open Access Journals (Sweden)

    Elisabetta eMueller

    2016-03-01

    Full Text Available Obesity represents a major risk factor for the development of a number of metabolic disorders, including cardiovascular disease and type 2 diabetes. Since the discovery that brown and beige fat cells exist in adult humans and contribute to energy expenditure, increasing interest has been devoted to the understanding of the molecular switches turning on calorie utilization. It has been reported that the ability of thermogenic tissues to burn energy declines during aging, possibly contributing to the development of metabolic dysfunction late in life. This review will focus on the recently identified transcriptional modulators of brown and beige cells and will discuss the potential impact of some of these thermogenic factors on age-associated metabolic disorders.

  19. Mir193b-365 is essential for brown fat differentiation.

    Science.gov (United States)

    Sun, Lei; Xie, Huangming; Mori, Marcelo A; Alexander, Ryan; Yuan, Bingbing; Hattangadi, Shilpa M; Liu, Qingqing; Kahn, C Ronald; Lodish, Harvey F

    2011-07-10

    Mammals have two principal types of fat. White adipose tissue primarily serves to store extra energy as triglycerides, whereas brown adipose tissue is specialized to burn lipids for heat generation and energy expenditure as a defence against cold and obesity. Recent studies have demonstrated that brown adipocytes arise in vivo from a Myf5-positive, myoblastic progenitor by the action of Prdm16 (PR domain containing 16). Here, we identified a brown-fat-enriched miRNA cluster, MiR-193b-365, as a key regulator of brown fat development. Blocking miR-193b and/or miR-365 in primary brown preadipocytes markedly impaired brown adipocyte adipogenesis by enhancing Runx1t1 (runt-related transcription factor 1; translocated to, 1) expression, whereas myogenic markers were significantly induced. Forced expression of Mir193b and/or Mir365 in C2C12 myoblasts blocked the entire programme of myogenesis, and, in adipogenic conditions, miR-193b induced myoblasts to differentiate into brown adipocytes. Mir193b-365 was upregulated by Prdm16 partially through Pparα. Our results demonstrate that Mir193b-365 serves as an essential regulator for brown fat differentiation, in part by repressing myogenesis.

  20. Browning of White Fat: Novel Insight Into Factors, Mechanisms, and Therapeutics.

    Science.gov (United States)

    Jeremic, Nevena; Chaturvedi, Pankaj; Tyagi, Suresh C

    2017-01-01

    What is more interesting about brown adipose tissue (BAT) is its ability to provide thermogenesis, protection against obesity by clearing triglycerides, releasing batokines, and mitigating insulin resistance. White adipose tissue (WAT) on the other hand stores excess energy and secretes some endocrine factors like leptin for regulating satiety. For the last decade there has been an increasing interest in the browning of fat keeping in view its beneficial effects on metabolic disorders and protection in the form of perivascular fat. Obesity is one such metabolic disorder that leads to significant morbidity and mortality from obesity-related disorders such as type 2 diabetes mellitus (T2D) and cardiovascular disease risk. Browning of white fat paves the way to restrict obesity and obesity related disorders. Although exercise has been the most common factor for fat browning; however, there are other factors that involve: (1) beta aminoisobutyric acid (BAIBA); (2) gamma amino butyric acid (GABA); (3) PPARɣ agonists; (4) JAK inhibition; and (5) IRISIN. In this review, we propose two novel factors musclin and TFAM for fat browning. Musclin a myokine released from muscles during exercise activates PPARɣ which induces browning of WAT that has beneficial metabolic and cardiac effects. TFAM is a transcription factor that induces mitochondrial biogenesis. Since BAT is rich in mitochondria, higher expression of TFAM in WAT or TFAM treatment in WAT cells can induce browning of WAT. We propose that fat browning can be used as a therapeutic tool for metabolic disorders and cardiovascular diseases. J. Cell. Physiol. 232: 61-68, 2017. © 2016 Wiley Periodicals, Inc.

  1. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

    DEFF Research Database (Denmark)

    Boström, Pontus; Wu, Jun; Jedrychowski, Mark P;

    2012-01-01

    of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly...

  2. Beige Adipocytes are a Distinct Type of Thermogenic Fat Cell in Mouse and Human

    OpenAIRE

    Wu, Jun; Boström, Pontus; Sparks, Lauren M; Ye, Li; Choi, Jang Hyun; Giang, An-Hoa; Khandekar, Melin; Nuutila, Pirjo; Schaart, Gert; Huang, Kexin; Tu, Hua; van Marken Lichtenbelt, Wouter D; Hoeks, Joris; Enerbäck, Sven; Schrauwen, Patrick

    2012-01-01

    Brown fat defends against hypothermia and obesity through thermogenesis mediated by mitochondrial UCP1. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here we report the cloning of “beige” cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but like classical brown fat, t...

  3. [Hibernoma: brown fat retroperitoneal tumor. Report of a pediatric case].

    Science.gov (United States)

    Collado, Laura; Sierre, Sergio; Bosalec, Andrea; Lipsich, José

    2011-12-01

    Hibernoma is a rare benign tumor of soft tissue, composed of brown fat. This tissue is predominant in hibernating animals and hence its name. Because of its rarity in Pediatrics and difficult diagnosis, we report a 3 month-old patient with a diagnosis consistent with an abdominal tumor. Ultrasound and computed tomography exams showed an infiltrative retroperitoneal tumor, with hypervascular and lipomatous features. After tumor excision, histopathological exam confirmed the diagnosis of hibernoma or brown fat tumor. This presentation describes the characteristics of this type of tumor, rare in children, and reviews the fatty tumors, according to their frequency in pediatric patients.

  4. Lipocytes (fat cells) (image)

    Science.gov (United States)

    ... to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person ...

  5. Novel function of the retinoblastoma protein in fat: regulation of white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; te Riele, Hein; Kristiansen, Karsten

    2004-01-01

    the major energy store and brown adipocytes being potent energy-dissipaters through thermogenesis. Yet, little is known about factors differentially regulating the formation of white and brown fat cells. Members of the retinoblastoma protein family (pRB, p107, p130) have been implicated in the regulation...... of adipocyte differentiation, and expression and phosphorylation of the three retinoblastoma family proteins oscillate in a characteristic manner during differentiation of the white preadipocyte cell line 3T3-L1. We have recently demonstrated a surprising function of the retinoblastoma protein...... in the regulation of white versus brown adipocyte differentiation in vitro and possibly in vivo. Here we summarize the current knowledge on the retinoblastoma protein in fat cells, with particular emphasis on its potential role in adipocyte lineage commitment and differentiation....

  6. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis.

    Science.gov (United States)

    Kajimura, Shingo; Saito, Masayuki

    2014-01-01

    Brown adipose tissue (BAT) is specialized to dissipate chemical energy in the form of heat as a defense against cold and excessive feeding. Interest in the field of BAT biology has exploded in the past few years because of the therapeutic potential of BAT to counteract obesity and obesity-related diseases, including insulin resistance. Much progress has been made, particularly in the areas of BAT physiology in adult humans, developmental lineages of brown adipose cell fate, and hormonal control of BAT thermogenesis. As we enter into a new era of brown fat biology, the next challenge will be to develop strategies for activating BAT thermogenesis in adult humans to increase whole-body energy expenditure. This article reviews the recent major advances in this field and discusses emerging questions. PMID:24188710

  7. Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Óscar; Díaz-Castroverde, Sabela; García-Gómez, Gema; Fernández, Silvia; Benito, Manuel

    2016-09-01

    Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID:27414981

  8. Role of energy metabolism in the brown fat gene program

    OpenAIRE

    Minwoo eNam; Marcus eCooper

    2015-01-01

    In murine and human brown adipose tissue (BAT), mitochondria are powerful generators of heat that safely metabolize fat, a feature that has great promise in the fight against obesity and diabetes. Recent studies suggest that the action of mitochondria extend beyond their conventional role as generators of heat. There is mounting evidence that impaired mitochondrial respiratory capacity is accompanied by attenuated expression of Ucp1 and other BAT-selective genes, implying that mitochondria ex...

  9. THE TRANSCRIPTION FACTOR GATA2 REGULATES DIFFERENTIATION OF BROWN ADIPOCYTES

    Science.gov (United States)

    Brown fat tissue is functionally different than the white fat, since brown fat burns lipid to generate heat for body temperature maintenance. However, brown fat cells share with white fat cells a similar molecular mechanism for fat cell formation. We have demonstrated previously that the GATA family...

  10. Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B.

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    Kosuke Matsuo

    Full Text Available Protein-tyrosine phosphatase 1B (PTP1B is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A and sumoylation-resistant (K/R PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR and insulin receptor substrate 1 (IRS1 tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B.

  11. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis

    OpenAIRE

    Qian, Shu-Wen; Tang, Yan; Li, Xi; Liu, Yuan; Zhang, You-you; Huang, Hai-yan; Xue, Rui-Dan; Yu, Hao-Yong; Guo, Liang; Gao, Hui-Di; Liu, Yan; Sun, Xia; Li, Yi-ming; Jia, Wei-Ping; Tang, Qi-Qun

    2013-01-01

    Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces “white adipocytes” with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP...

  12. Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

    Directory of Open Access Journals (Sweden)

    Dong Hyun Jo

    Full Text Available Anti-vascular endothelial growth factor (VEGF agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

  13. Adipose VEGF Links the White-to-Brown Fat Switch With Environmental, Genetic, and Pharmacological Stimuli in Male Mice.

    Science.gov (United States)

    During, Matthew J; Liu, Xianglan; Huang, Wei; Magee, Daniel; Slater, Andrew; McMurphy, Travis; Wang, Chuansong; Cao, Lei

    2015-06-01

    Living in an enriched environment (EE) decreases adiposity, increases energy expenditure, causes resistance to diet induced obesity, and induces brown-like (beige) cells in white fat via activating a hypothalamic-adipocyte axis. Here we report that EE stimulated vascular endothelial growth factor (VEGF) expression in a fat depot-specific manner prior to the emergence of beige cells. The VEGF up-regulation was independent of hypoxia but required intact sympathetic tone to the adipose tissue. Targeted adipose overexpression of VEGF reproduced the browning effect of EE. Adipose-specific VEGF knockout or pharmacological VEGF blockade with antibodies abolished the induction of beige cell by EE. Hypothalamic brain-derived neurotrophic factor stimulated by EE regulated the adipose VEGF expression, and VEGF signaling was essential to the hypothalamic brain-derived neurotrophic factor-induced white adipose tissue browning. Furthermore, VEGF signaling was essential to the beige cells induction by exercise, a β3-adrenergic agonist, and a peroxisome proliferator-activated receptor-γ ligand, suggesting a common downstream pathway integrating diverse upstream mechanisms. Exploiting this pathway may offer potential therapeutic interventions to obesity and metabolic diseases. PMID:25763639

  14. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

    NARCIS (Netherlands)

    Berbeé, J.F.P.; Boon, M.R.; Khedoe, P.P.S.J.; Bartelt, A.; Schlein, C.; Worthmann, A.; Kooijman, S.; Hoeke, G.; Mol, I.M.; John, C.; Jung, C.; Vazirpanah, N.; Brouwers, L.P.J.; Gordts, P.L.S.M.; Esko, J.D.; Hiemstra, P.S.; Havekes, L.M.; Scheja, L.; Heeren, J.; Rensen, P.C.N.

    2015-01-01

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic rece

  15. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis.

    Science.gov (United States)

    Qian, Shu-Wen; Tang, Yan; Li, Xi; Liu, Yuan; Zhang, You-You; Huang, Hai-Yan; Xue, Rui-Dan; Yu, Hao-Yong; Guo, Liang; Gao, Hui-Di; Liu, Yan; Sun, Xia; Li, Yi-Ming; Jia, Wei-Ping; Tang, Qi-Qun

    2013-02-26

    Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.

  16. Assessment of oxidative metabolism in Brown Fat using PET imaging

    OpenAIRE

    Otto eMuzik; Mangner, Thomas J.; Granneman, James G.

    2012-01-01

    Objective: Although it has been believed that brown adipose tissue (BAT) depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog FDG has shown unequivocally the existence of functional BAT in humans. The objective of this study was to determine, using dynamic oxygen-15 (15O) PET imaging, to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and FDG tracer uptake....

  17. Vascular rarefaction mediates whitening of brown fat in obesity

    OpenAIRE

    Shimizu, Ippei; Aprahamian, Tamar; Kikuchi, Ryosuke; Shimizu, Ayako; Papanicolaou, Kyriakos N.; MacLauchlan, Susan; Maruyama, Sonomi; Walsh, Kenneth

    2014-01-01

    Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet ...

  18. Assessment of Oxidative Metabolism in Brown Fat Using PET Imaging

    OpenAIRE

    Muzik, Otto; Mangner, Thomas J.; Granneman, James G.

    2012-01-01

    Objective: Although it has been believed that brown adipose tissue (BAT) depots disappear shortly after the perinatal period in humans, positron emission tomography (PET) imaging using the glucose analog 18F-deoxy-d-glucose (FDG) has shown unequivocally the existence of functional BAT in humans, suggesting that most humans have some functional BAT. The objective of this study was to determine, using dynamic oxygen-15 (15O) PET imaging, to what extent BAT thermogenesis is activated in adults d...

  19. [Human brown adipose tissue].

    Science.gov (United States)

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  20. Ubc9 Impairs Activation of the Brown Fat Energy Metabolism Program in Human White Adipocytes.

    Science.gov (United States)

    Hartig, Sean M; Bader, David A; Abadie, Kathleen V; Motamed, Massoud; Hamilton, Mark P; Long, Weiwen; York, Brian; Mueller, Michaela; Wagner, Martin; Trauner, Michael; Chan, Lawrence; Bajaj, Mandeep; Moore, David D; Mancini, Michael A; McGuire, Sean E

    2015-09-01

    Insulin resistance and type 2 diabetes mellitus (T2DM) result from an inability to efficiently store and catabolize surplus energy in adipose tissue. Subcutaneous adipocytes protect against insulin resistance and T2DM by coupling differentiation with the induction of brown fat gene programs for efficient energy metabolism. Mechanisms that disrupt these programs in adipocytes are currently poorly defined, but represent therapeutic targets for the treatment of T2DM. To gain insight into these mechanisms, we performed a high-throughput microscopy screen that identified ubiquitin carrier protein 9 (Ubc9) as a negative regulator of energy storage in human sc adipocytes. Ubc9 depletion enhanced energy storage and induced the brown fat gene program in human sc adipocytes. Induction of adipocyte differentiation resulted in decreased Ubc9 expression commensurate with increased brown fat gene expression. Thiazolidinedione treatment reduced the interaction between Ubc9 and peroxisome proliferator-activated receptor (PPAR)γ, suggesting a mechanism by which Ubc9 represses PPARγ activity. In support of this hypothesis, Ubc9 overexpression remodeled energy metabolism in human sc adipocytes by selectively inhibiting brown adipocyte-specific function. Further, Ubc9 overexpression decreased uncoupling protein 1 expression by disrupting PPARγ binding at a critical uncoupling protein 1 enhancer region. Last, Ubc9 is significantly elevated in sc adipose tissue isolated from mouse models of insulin resistance as well as diabetic and insulin-resistant humans. Taken together, our findings demonstrate a critical role for Ubc9 in the regulation of sc adipocyte energy homeostasis.

  1. LSD1 Interacts with Zfp516 to Promote UCP1 Transcription and Brown Fat Program

    OpenAIRE

    Audrey Sambeat; Olga Gulyaeva; Jon Dempersmier; Kevin M. Tharp; Andreas Stahl; Sarah M. Paul; Hei Sook Sul

    2016-01-01

    Zfp516, a brown fat (BAT)-enriched and cold-inducible transcription factor, promotes transcription of UCP1 and other BAT-enriched genes for non-shivering thermogenesis. Here, we identify lysine-specific demethylase 1 (LSD1) as a direct binding partner of Zfp516. We show that, through interaction with Zfp516, LSD1 is recruited to UCP1 and other BAT-enriched genes, such as PGC1α, to function as a coactivator by demethylating H3K9. We also show that LSD1 is induced during brown adipogenesis and ...

  2. Fat accumulation in differentiated brown adipocytes is linked with expression of Hox genes.

    Science.gov (United States)

    Singh, Smita; Rajput, Yudhishthir S; Barui, Amit K; Sharma, Rajan; Datta, Tirtha K

    2016-03-01

    Homeobox (Hox) genes are involved in body plan of embryo along the anterior-posterior axis. Presence of several Hox genes in white adipose tissue (WAT) and brown adipose tissue (BAT) is indicative of involvement of Hox genes in adipogenesis. We propose that differentiation inducing agents viz. isobutyl-methyl-xanthine (IBMX), indomethacin, dexamethasone (DEX), triiodothyronine (T3) and insulin may regulate differentiation in brown adipose tissue through Hox genes. In vitro culture of brown fat stromalvascular fraction (SVF) in presence or absence of differentiation inducing agents was used for establishing relationship between fat accumulation in differentiated adipocytes and expression of Hox genes. Relative expression of Pref1, UCP1 and Hox genes was determined in different stages of adipogenesis. Presence or absence of IBMX, indomethacin and DEX during differentiation of proliferated pre-adipocytes resulted in marked differences in expression of Hox genes and lipid accumulation. In presence of these inducing agents, lipid accumulation as well as expression of HoxA1, HoxA5, HoxC4 &HoxC8 markedly enhanced. Irrespective of presence or absence of T3, insulin down regulates HoxA10. T3 results in over expression of HoxA5, HoxC4 and HoxC8 genes, whereas insulin up regulates expression of only HoxC8. Findings suggest that accumulation of fat in differentiated adipocytes is linked with expression of Hox genes.

  3. Assessment of oxidative metabolism in Brown Fat using PET imaging

    Directory of Open Access Journals (Sweden)

    Otto eMuzik

    2012-02-01

    Full Text Available Objective: Although it has been believed that brown adipose tissue (BAT depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog FDG has shown unequivocally the existence of functional BAT in humans. The objective of this study was to determine, using dynamic oxygen-15 (15O PET imaging, to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and FDG tracer uptake.Methods: Fourteen adult normal subjects (9F/5M, 30+7 years underwent triple oxygen scans (H215O, C15O, 15O2 as well as indirect calorimetric measurements at rest and following exposure to mild cold (60F. Subjects were divided into two groups (BAT+ and BAT- based on the presence or absence of FDG tracer uptake (SUV > 2 in supraclavicular BAT. Blood flow (BF and oxygen extraction fraction (OEF was calculated from dynamic PET scans at the location of BAT, muscle and white adipose tissue (WAT. The metabolic rate of oxygen (MRO2 in BAT was determined and used to calculate the contribution of activated BAT to daily energy expenditure (DEE.Results: The median mass of activated BAT in the BAT+ group (5F, 31+8yrs was 52.4 g (14-68g and was 1.7 g (0-6.3g in the BAT- group (5M/4F, 29+6yrs. SUV values were significantly higher in the BAT+ as compared to the BAT- group (7.4+3.7 vs 1.9+0.9; p=0.03. BF values in BAT were significantly higher in the BAT+ as compared to the BAT- group (13.1+4.4 vs 5.7+1.1 ml/100g/min, p=0.03, but were similar in WAT (4.1+1.6 vs 4.2+1.8 ml/100g/min and muscle (3.7+0.8 vs 3.3+1.2 ml/100g/min. Calculated MRO2 values in BAT increased from 0.95+0.74 to 1.62+0.82 ml/100g/min in the BAT+ group and were significantly higher than those determined in the BAT- group (0.43+0.27 vs 0.56+0.24; p=0.67. The DEE associated with BAT oxidative metabolism was highly variable in the BAT+ group, with an average of 5.5+6.4 kcal/day (range 0.57–15.3 kcal/day.

  4. Brown adipose tissue quantification in human neonates using water-fat separated MRI.

    Directory of Open Access Journals (Sweden)

    Jerod M Rasmussen

    Full Text Available There is a major resurgence of interest in brown adipose tissue (BAT biology, particularly regarding its determinants and consequences in newborns and infants. Reliable methods for non-invasive BAT measurement in human infants have yet to be demonstrated. The current study first validates methods for quantitative BAT imaging of rodents post mortem followed by BAT excision and re-imaging of excised tissues. Identical methods are then employed in a cohort of in vivo infants to establish the reliability of these measures and provide normative statistics for BAT depot volume and fat fraction. Using multi-echo water-fat MRI, fat- and water-based images of rodents and neonates were acquired and ratios of fat to the combined signal from fat and water (fat signal fraction were calculated. Neonatal scans (n = 22 were acquired during natural sleep to quantify BAT and WAT deposits for depot volume and fat fraction. Acquisition repeatability was assessed based on multiple scans from the same neonate. Intra- and inter-rater measures of reliability in regional BAT depot volume and fat fraction quantification were determined based on multiple segmentations by two raters. Rodent BAT was characterized as having significantly higher water content than WAT in both in situ as well as ex vivo imaging assessments. Human neonate deposits indicative of bilateral BAT in spinal, supraclavicular and axillary regions were observed. Pairwise, WAT fat fraction was significantly greater than BAT fat fraction throughout the sample (ΔWAT-BAT = 38 %, p<10(-4. Repeated scans demonstrated a high voxelwise correlation for fat fraction (Rall = 0.99. BAT depot volume and fat fraction measurements showed high intra-rater (ICCBAT,VOL = 0.93, ICCBAT,FF = 0.93 and inter-rater reliability (ICCBAT,VOL = 0.86, ICCBAT,FF = 0.93. This study demonstrates the reliability of using multi-echo water-fat MRI in human neonates for quantification throughout the torso of BAT depot volume and fat

  5. Differentiation of human adipose-derived stem cells into brite (brown-in-white adipocytes

    Directory of Open Access Journals (Sweden)

    Didier F Pisani

    2011-11-01

    Full Text Available It is well established now that adult humans possess active brown adipose tissue which represents a potential pharmacological target to combat obesity and associated diseases. We had shown previously that human multipotent adipose-derived stem (hMADS cells are able to differentiate into cells which exhibit the key properties of human white adipocytes, and to convert into functional brown adipocytes upon PPARγ activation that could explain UCP1-expressing cells within islets surrounded by white adipocytes. Herein we further characterize hMADS cells differentiation into brown adipocytes that behave like mouse brite adipocytes previously described. We analyzed the expression of gene markers known to be associated with mouse white and brown adipocytes. When shifting from a white to a brown fat cell phenotype, the striking enhancement of uncoupling activity appears mainly due, if not all, to an increase in UCP1 expression whereas induction of UCP2 is weak and UCP3 expression is unchanged. Conversion of white hMADS adipocytes is dependent on PPARγ activation with rosiglitazone as the most potent agonist and is inhibited by a PPARγ antagonist. Furthermore our data show that, in contrast to mouse cellular models, hMADS cells conversion into brown adipocytes is not induced by BMP7 treatment and not modulated by activation of the Hedgehog pathway. No primary or clonal precursor cells of human brown adipocytes have been obtained so far that can be used as a tool to develop therapeutic drugs and to gain further insights into the molecular mechanisms of brown adipogenesis in humans. Thus hMADS cells represent a suitable cell model to delineate the formation and/or the uncoupling capacity of human brown/brite adipocytes that could help to dissipate caloric excess intake among individuals.

  6. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.

    Science.gov (United States)

    DiSilvestro, David J; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L James; Kalyanasundaram, Anuradha; Gilor, Chen L; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  7. A role for phosphodiesterase 3B in acquisition of brown fat characteristics by white adipose tissue in male mice.

    Science.gov (United States)

    Guirguis, Emilia; Hockman, Steven; Chung, Youn Wook; Ahmad, Faiyaz; Gavrilova, Oksana; Raghavachari, Nalini; Yang, Yanqin; Niu, Gang; Chen, Xiaoyuan; Yu, Zu Xi; Liu, Shiwei; Degerman, Eva; Manganiello, Vincent

    2013-09-01

    Obesity is linked to various diseases, including insulin resistance, diabetes, and cardiovascular disorders. The idea of inducing white adipose tissue (WAT) to assume characteristics of brown adipose tissue (BAT), and thus gearing it to fat burning instead of storage, is receiving serious consideration as potential treatment for obesity and related disorders. Phosphodiesterase 3B (PDE3B) links insulin- and cAMP-signaling networks in tissues associated with energy metabolism, including WAT. We used C57BL/6 PDE3B knockout (KO) mice to elucidate mechanisms involved in the formation of BAT in epididymal WAT (EWAT) depots. Examination of gene expression profiles in PDE3B KO EWAT revealed increased expression of several genes that block white and promote brown adipogenesis, such as C-terminal binding protein, bone morphogenetic protein 7, and PR domain containing 16, but a clear BAT-like phenotype was not completely induced. However, acute treatment of PDE3B KO mice with the β3-adrenergic agonist, CL316243, markedly increased the expression of cyclooxygenase-2, which catalyzes prostaglandin synthesis and is thought to be important in the formation of BAT in WAT and the elongation of very long-chain fatty acids 3, which is linked to BAT recruitment upon cold exposure, causing a clear shift toward fat burning and the induction of BAT in KO EWAT. These data provide insight into the mechanisms of BAT formation in mouse EWAT, suggesting that, in a C57BL/6 background, an increase in cAMP, caused by ablation of PDE3B and administration of CL316243, may promote differentiation of prostaglandin-responsive progenitor cells in the EWAT stromal vascular fraction into functional brown adipocytes.

  8. Effect of Chronic Athletic Activity on Brown Fat in Young Women.

    Directory of Open Access Journals (Sweden)

    Vibha Singhal

    Full Text Available The effect of chronic exercise activity on brown adipose tissue (BAT is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT.We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status.The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes between 18-25 years of age. Athletes were either oligo-amenorrheic (n = 8 or eumenorrheic (n = 8.We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition.Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002, higher percent lean mass (p = 0.01 and trended higher in REE (p = 0.09. BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively. We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02.BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02, and positively with percent body fat, irisin and thyroid hormones.Our study shows a trend for lower BAT in young female

  9. Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes

    DEFF Research Database (Denmark)

    Elabd, Christian; Chiellini, Chiara; Carmona, Mamen;

    2009-01-01

    In contrast to the earlier contention, adult humans have been shown recently to possess active brown adipose tissue with a potential of being of metabolic significance. Up to now, brown fat precursor cells have not been available for human studies. We have shown previously that human multipotent...... adipose-derived stem (hMADS) cells exhibit a normal karyotype and high self-renewal ability; they are known to differentiate into cells that exhibit the key properties of human white adipocytes, that is, uncoupling protein two expression, insulin-stimulated glucose uptake, lipolysis in response to beta......-agonists and atrial natriuretic peptide, and release of adiponectin and leptin. Herein, we show that, upon chronic exposure to a specific PPARgamma but not to a PPARbeta/delta or a PPARalpha agonist, hMADS cell-derived white adipocytes are able to switch to a brown phenotype by expressing both uncoupling protein one...

  10. Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1

    Science.gov (United States)

    Wang, Songbo; Liang, Xingwei; Yang, Qiyuan; Fu, Xing; Rogers, Carl J.; Zhu, Meijun; Rodgers, B. D.; Jiang, Qingyan; Dodson, Michael V.; Du, Min

    2014-01-01

    Objective Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus, we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). Methods CD1 female mice (5-month-old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. Results Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers including uncoupling protein 1 (UCP1), PR domain-containing 16 (PRDM16), Cell death-inducing DFFA-like effector A (Cidea), elongation of very long chain fatty acids protein 3 (Elovl3), peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), cytochrome C and pyruvate dehydrogenase (PDH) in differentiated iWAT stromal vascular cells (SVC), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. Conclusion Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial anti-obesity effects may be partly due to the browning of WAT and as a consequence, increased oxygen consumption. PMID:25761413

  11. The biological clock is regulated by adrenergic signaling in brown fat but is dispensable for cold-induced thermogenesis.

    Directory of Open Access Journals (Sweden)

    Siming Li

    Full Text Available The biological clock plays an important role in integrating nutrient and energy metabolism with other cellular processes. Previous studies have demonstrated that core clock genes are rhythmically expressed in peripheral tissues, including the liver, skeletal muscle, pancreatic islets, and white and brown adipose tissues. These peripheral clocks are entrained by physiological cues, thereby aligning the circadian pacemaker to tissue functions. The mechanisms that regulate brown adipose tissue clock in response to physiological signals remain poorly understood. Here we found that the expression of core clock genes is highly responsive to cold exposure in brown fat, but not in white fat. This cold-inducible regulation of the clock network is mediated by adrenergic receptor activation and the transcriptional coactivator PGC-1α. Brown adipocytes in mice lacking a functional clock contain large lipid droplets accompanied by dysregulation of genes involved in lipid metabolism and adaptive thermogenesis. Paradoxically, the "clockless" mice were competent in maintaining core body temperature during cold exposure. These studies elucidated the presence of adrenergic receptor/clock crosstalk that appears to be required for normal thermogenic gene expression in brown fat.

  12. Brown but not white adipose cells synthesize omega-3 docosahexaenoic acid in culture.

    Science.gov (United States)

    Qin, Xia; Park, Hui Gyu; Zhang, Ji Yao; Lawrence, Peter; Liu, Guowen; Subramanian, Nivetha; Kothapalli, Kumar S D; Brenna, J Thomas

    2016-01-01

    Adipose tissue is a complex endocrine organ which coordinates several crucial biological functions including fatty acid metabolism, glucose metabolism, energy homeostasis, and immune function. Brown adipose tissue (BAT) is most abundant in young infants during the brain growth spurt when demands for omega-3 docosahexaenoic acid (DHA, 22:6n-3) is greatest for brain structure. Our aim was to characterize relative biosynthesis of omega-3 long chain polyunsaturated fatty acids (LCPUFA) from precursors in cultured white (WAT) and brown (BAT) cells and study relevant gene expression. Mouse WAT and BAT cells were grown in regular DMEM media to confluence, and differentiation was induced. At days 0 and 8 cells were treated with albumin bound d5-18:3n-3 (d5-ALA) and analyzed 24h later. d5-ALA increased cellular eicosapentaenoic acid (EPA, 20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in undifferentiated BAT cells, whereas differentiated BAT cells accumulated 20:4n-3, EPA and DPA. DHA as a fraction of total omega-3 LCPUFA was greatest in differentiated BAT cells compared to undifferentiated cells. Undifferentiated WAT cells accumulated EPA, whereas differentiated cells accumulated DPA. WAT accumulated trace newly synthesized DHA. Zic1 a classical brown marker and Prdm16 a key driver of brown fat cell fate are expressed only in BAT cells. Ppargc1a is 15 fold higher in differentiated BAT cells. We conclude that in differentiated adipose cells accumulating fat, BAT cells but not WAT cells synthesize DHA, supporting the hypothesis that BAT is a net producer of DHA.

  13. LSD1 Interacts with Zfp516 to Promote UCP1 Transcription and Brown Fat Program

    Directory of Open Access Journals (Sweden)

    Audrey Sambeat

    2016-06-01

    Full Text Available Zfp516, a brown fat (BAT-enriched and cold-inducible transcription factor, promotes transcription of UCP1 and other BAT-enriched genes for non-shivering thermogenesis. Here, we identify lysine-specific demethylase 1 (LSD1 as a direct binding partner of Zfp516. We show that, through interaction with Zfp516, LSD1 is recruited to UCP1 and other BAT-enriched genes, such as PGC1α, to function as a coactivator by demethylating H3K9. We also show that LSD1 is induced during brown adipogenesis and that LSD1 and its demethylase activity is required for the BAT program. Furthermore, we show that LSD1 ablation in mice using Myf5-Cre alters embryonic BAT development. Moreover, BAT-specific deletion of LSD1 via the use of UCP1-Cre impairs the BAT program and BAT development, making BAT resemble WAT, reducing thermogenic activity and promoting obesity. Finally, we demonstrate an in vivo requirement of the Zfp516-LSD1 interaction for LSD1 function in BAT gene activation.

  14. LSD1 Interacts with Zfp516 to Promote UCP1 Transcription and Brown Fat Program.

    Science.gov (United States)

    Sambeat, Audrey; Gulyaeva, Olga; Dempersmier, Jon; Tharp, Kevin M; Stahl, Andreas; Paul, Sarah M; Sul, Hei Sook

    2016-06-14

    Zfp516, a brown fat (BAT)-enriched and cold-inducible transcription factor, promotes transcription of UCP1 and other BAT-enriched genes for non-shivering thermogenesis. Here, we identify lysine-specific demethylase 1 (LSD1) as a direct binding partner of Zfp516. We show that, through interaction with Zfp516, LSD1 is recruited to UCP1 and other BAT-enriched genes, such as PGC1α, to function as a coactivator by demethylating H3K9. We also show that LSD1 is induced during brown adipogenesis and that LSD1 and its demethylase activity is required for the BAT program. Furthermore, we show that LSD1 ablation in mice using Myf5-Cre alters embryonic BAT development. Moreover, BAT-specific deletion of LSD1 via the use of UCP1-Cre impairs the BAT program and BAT development, making BAT resemble WAT, reducing thermogenic activity and promoting obesity. Finally, we demonstrate an in vivo requirement of the Zfp516-LSD1 interaction for LSD1 function in BAT gene activation. PMID:27264172

  15. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation

    DEFF Research Database (Denmark)

    Barbatelli, G.; Murano, I.; Madsen, Lise;

    2010-01-01

    The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT after cold acclimatization have a mixed morphology (paucilocular adipocytes). These cells also had...... enhanced expression of the thermogenic genes and of genes expressed selectively in brown adipose tissue (iBAT) and in both interscapular BAT and WAT. ß3-adrenoceptor suppression blunted their expression only in WAT. Furthermore, cold acclimatization induced an increased WAT expression of the gene coding...... a mixed mitochondrioma with classic "brown" and "white" mitochondria, suggesting intermediate steps in the process of direct transformation of white into brown adipocytes (transdifferentiation). Quantitative electron microscopy disclosed that cold exposure (6°C for 10 days) did not induce an increase...

  16. Medium-Chain Triglyceride Activated Brown Adipose Tissue and Induced Reduction of Fat Mass in C57BL/6J Mice Fed High-fat Diet

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yong; XUE Chang Yong; XU Qing; LIU Ying Hua; ZHANG Xin Sheng; WANG Jin; YU Xiao Ming; ZHANG Rong Xin; XUE Chao; YANG Xue Yan

    2015-01-01

    Objective To investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT). Methods 30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein ofβ3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05). Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

  17. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Steven D Kunkel

    Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  18. GQ-16, a TZD-Derived Partial PPARγ Agonist, Induces the Expression of Thermogenesis-Related Genes in Brown Fat and Visceral White Fat and Decreases Visceral Adiposity in Obese and Hyperglycemic Mice

    Science.gov (United States)

    Coelho, Michella S.; de Lima, Caroline L.; Royer, Carine; Silva, Janaina B.; Oliveira, Fernanda C. B.; Christ, Camila G.; Pereira, Sidney A.; Bao, Sonia N.; Lima, Maria C. A.; Pitta, Marina G. R.; Pitta, Ivan R.; Neves, Francisco A. R.; Amato, Angélica A.

    2016-01-01

    Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis-related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARγ agonist may

  19. Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats

    OpenAIRE

    Betz, Matthias J.; Maximilian Bielohuby; Brigitte Mauracher; William Abplanalp; Hans-Helge Müller; Korbinian Pieper; Juliane Ramisch; Tschöp, Matthias H.; Felix Beuschlein; Martin Bidlingmaier; Marc Slawik

    2012-01-01

    UNLABELLED: Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets. METHODS: Male Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4...

  20. Isoenergetic feeding of low carbohydrate-high fat diets does not increase brown adipose tissue thermogenic capacity in rats

    OpenAIRE

    Betz, Matthias J.; Bielohuby, Maximilian; Mauracher, Brigitte; Abplanalp, William; Müller, Hans-Helge; Pieper, Korbinian; Ramisch, Juliane; Tschöp, Matthias H.; Beuschlein, Felix; Bidlingmaier, Martin; Slawik, Marc

    2012-01-01

    Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets. Methods: Male Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4 weeks...

  1. Lower weight gain and hepatic lipid content in hamsters fed high fat diets supplemented with white rice protein, brown rice protein, and soy protein and their hydrolysates

    Science.gov (United States)

    The physiological effects of the hydrolysates from white rice, brown rice, and soy isolate were compared to the original protein source. White rice, brown rice, and soy protein were hydrolyzed with the food grade enzyme, alcalase2.4 L®. Male Syrian hamsters were fed high-fat diets containing eithe...

  2. Inherent plasticity of brown adipogenesis in white fat of mice allows for recovery from effects of post-natal malnutrition.

    Directory of Open Access Journals (Sweden)

    Leslie P Kozak

    Full Text Available Interscapular brown adipose tissue (iBAT is formed during fetal development and stable for the life span of the mouse. In addition, brown adipocytes also appear in white fat depots (wBAT between 10 and 21 days of age in mice maintained at a room temperature of 23 °C. However, this expression is transient. By 60 days of age the brown adipocytes have disappeared, but they can re-emerge if the adult mouse is exposed to the cold (5 °C or treated with β3-adrenergic agonists. Since the number of brown adipocytes that can be induced in white fat influences the capacity of the mouse to resist the obese state, we determined the effects of the nutritional conditions on post-natal development (birth to 21 days of wBAT and its long-term effects on diet-induced obesity (DIO. Under-nutrition caused essentially complete suppression of wBAT in inguinal fat at 21 days of age, as indicated by expression of Ucp1 and genes of mitochondrial structure and function based upon microarray and qRT-PCR analysis, whereas over-nutrition had no discernible effects on wBAT induction. Surprisingly, the suppression of wBAT at 21 days of age did not affect DIO in adult mice maintained at 23 °C, nor did it affect the reduction in obesity or cold tolerance when DIO mice were exposed to the cold at 5 °C for one week. Gene expression analysis indicated that mice raised under conditions that suppressed wBAT at 21 days of age were able to normally induce wBAT as adults. Therefore, neither severe hypoleptinemia nor hypoinsulinemia during suckling permanently impaired brown adipogenesis in white fat. In addition, energy balance studies of DIO mice exposed to cold indicates that mice with reduced adipose stores preferentially increased food intake, whereas those with larger adipose tissue depots preferred to utilize energy from their adipose stores.

  3. Effects of the Polysaccharide from the Sporophyll of Brown Alga Undaria Pinnatifida on Serum Lipid Profile and Fat Tissue Accumulation in Rats Fed a High-Fat Diet.

    Science.gov (United States)

    Kim, Byoung-Mok; Park, Jae-Ho; Kim, Dong-Soo; Kim, Young-Myung; Jun, Joon-Young; Jeong, In-Hak; Chi, Young-Min

    2016-07-01

    We investigated the effects of the polysaccharide from the sporophyll of a selected brown alga Undaria pinnatifida on serum lipid profile, fat tissue accumulation, and gastrointestinal transit time in rats fed a high-fat diet. The algal polysaccharide (AP) was prepared by the treatment of multiple cellulase-producing fungi Trichoderma reesei and obtained from the sporophyll with a yield of 38.7% (dry basis). The AP was mostly composed of alginate and fucoidan (up to 89%) in a ratio of 3.75:1. The AP was added to the high-fat diet in concentrations of 0.6% and 1.7% and was given to male Sprague-Dawley rats (5-wk-old) for 5 wk. The 1.7% AP addition notably reduced body weight gain and fat tissue accumulation, and it improved the serum lipid profile, including triglycerides, total cholesterol, and very low-density lipoprotein-cholesterol. The effects were associated with increased feces weight and shortened gastrointestinal transit time. In addition, the lipid peroxidation of the liver was decreased in both groups. PMID:27384013

  4. Gene expression profiles reveal effect of a high-fat diet on the development of white and brown adipose tissues.

    Science.gov (United States)

    Kim, Hyeng-Soo; Ryoo, Zae Young; Choi, Sang Un; Lee, Sanggyu

    2015-07-01

    Because of the recent discovery of brown adipose tissues tissue in adult humans, brown adipose tissues have garnered additional attention. Many studies have attempted to transform the precursor cells within the white adipocyte cultures to Brite (brown-in-white) cells by using genomic modification or pharmacological activation in order to determine the therapeutic effect of obesity. However, genome-scale analysis of the genetic factors governing the development of white and brown adipose tissues remains incomplete. In order to identify the key genes that regulate the development of white and brown adipose tissues in mice, a transcriptome analysis was performed on the adipose tissues. Network analysis of differentially expressed genes indicated that Trim30 and Ucp3 play pivotal roles in energy balance and glucose homeostasis. In addition, it was discovered that identical biological processes and pathways in the white and brown adipose tissues might be regulated by different genes. Trim30 and Ucp3 might be used as genetic markers to precisely represent the stage of obesity during the early and late stages of adipose tissue development, respectively. These results may provide a stepping-stone for future obesity-related studies.

  5. Chronic activation of pattern recognition receptors suppresses brown adipogenesis of multipotent mesodermal stem cells and brown pre-adipocytes.

    Science.gov (United States)

    Bae, Jiyoung; Chen, Jiangang; Zhao, Ling

    2015-06-01

    Brown adipose tissue (BAT) holds promise to combat obesity through energy-spending, non-shivering thermogenesis. Understanding of regulation of BAT development can lead to novel strategies to increase BAT mass and function for obesity treatment and prevention. Here, we report the effects of chronic activation of PRR on brown adipogenesis of multipotent mesodermal stem C3H10T1/2 cells and immortalized brown pre-adipocytes from the classical interscapular BAT of mice. Activation of NOD1, TLR4, or TLR2 by their respective synthetic ligand suppressed brown marker gene expression and lipid accumulation during differentiation of brown-like adipocytes of C3H10T1/2. Activation of the PRR only during the commitment was sufficient to suppress the differentiation. PRR activation suppressed PGC-1α mRNA, but induced PRDM16 mRNA at the commitment. Consistently, PRR activation suppressed the differentiation of immortalized brown pre-adipocytes. Activation of PRR induced NF-κB activation in both cells, which correlated with their abilities to suppress PPARγ transactivation, a critical event for brown adipogenesis. Taken together, our results demonstrate that chronic PRR activation suppressed brown adipogenesis of multipotent mesodermal stem cells and brown pre-adipocytes, possibly through suppression of PPARγ transactivation. The results suggest that anti- inflammatory therapies targeting PRRs may be beneficial for the BAT development.

  6. Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

    DEFF Research Database (Denmark)

    McGlashon, Jacob M; Gorecki, Michelle C; Kozlowski, Amanda E;

    2015-01-01

    adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating...... diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white...

  7. Anti-obesity effects of germinated brown rice extract through down-regulation of lipogenic genes in high fat diet-induced obese mice.

    Science.gov (United States)

    Ho, Jin-Nyoung; Son, Mi-Eun; Lim, Won-Chul; Lim, Seung-Taik; Cho, Hong-Yon

    2012-01-01

    Lipid accumulation using Oil Red O dye was measured in 3T3-L1 murine adipocytes to examine the anti-obesity effect of four types of germinated rice, including germinated brown rice (GBR), germinated waxy brown rice (GWBR), germinated black rice (GB-R), and germinated waxy black rice (GWB-R). GBR methanol extract exhibited the highest suppression of lipid accumulation in the 3T3-L1 cell line and also the anti-obesity effect of GBR on high fat induced-obese mice. The mice were divided into three groups and were administered: ND, a normal diet; HFD control, a high fat diet; and GBR, a high fat diet plus 0.15% GBR methanol extract for 7 weeks. GBR administration significantly decreased body weight gain and lipid accumulation in the liver and epididymal adipose tissue as compared to the HFD control group. In addition, serum triglycerides (TGs) and total cholesterol (TC) levels were significantly decreased by following GBR administration compared with those in the HFD control group, whereas the high-density lipoprotein (HDL) cholesterol level increased. Furthermore, the mRNA levels of adipogenic transcriptional factors, such as CCAAT enhancer binding protein (C/EBP)-α, sterol regulatory element-binding protein (SREBP)-1c, and peroxisome proliferator activated receptors (PPAR)-γ, and related genes (aP2, FAS), decreased significantly. Taken together, GBR administration suppressed body weight gain and lipid accumulation in the liver and epididymal adipocytes, and improved serum lipid profiles, in part, by controlling adipogenesis through a reduction in transcriptional factors. These results suggest that GBR is a potential agent against obesity.

  8. Langerhans Cell Histiocytosis Presenting as Brown Lichenoid Patches

    OpenAIRE

    Kwon, Hyuk; Lee, Jang Hyun; Kim, Sung Keun; Park, Young Lip; Lee, Jong Suk; Cho, Moon Kyun

    2009-01-01

    Langerhans cell histiocytosis (LCH) is related diseases characterized by proliferation of Langerhans cell with involvement of bone, skin, lung and other organs. LCH usually occurs in childhood and are presented as multiple small papules or eczematoid lesion mostly. We report a 50-year-old man with 3 brown lichenoid patches on left dorsal foot. He was diagnosed pulmonary LCH 5 years ago. Typical LC cells on skin lesion and CD1 complex positive staining confirm the diagnosis of LCH. We consider...

  9. Adipose-derived regenerative cell (ADRC)-enriched fat grafting: optimal cell concentration and effects on grafted fat characteristics

    OpenAIRE

    Kakudo, Natsuko; Tanaka, Yoshihito; Morimoto, Naoki; Ogawa, Takeshi; Kushida, Satoshi; Hara, Tomoya; Kusumoto, Kenji

    2013-01-01

    Background To overcome the absorption of traditional fat grafting, techniques for adipose-derived regenerative cell (ADRC)-enriched fat grafting are currently being adapted for practical application. The Celution®800/CRS (Cytori Therapeutics, San Diego, CA) has enabled rapid grafting of the patient’s own freshly harvested ADRCs without requiring a culturing step. However, the optimal cell concentration and the effects of ADRCs on the characteristics of grafted fat after free fat grafting rema...

  10. Isoenergetic feeding of low carbohydrate-high fat diets does not increase brown adipose tissue thermogenic capacity in rats.

    Directory of Open Access Journals (Sweden)

    Matthias J Betz

    Full Text Available UNLABELLED: Low-carbohydrate, high-fat (LC-HF diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT morphology and function following exposure to different LC-HF diets. METHODS: Male Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4 weeks. The diets had the following macronutrient composition (% metabolizable energy: carbohydrates, fat, protein: control (64.3/16.7/19, LC-HF-low protein (LC-HF-LP, 1.7/92.8/5.5, LC-HF-normal-protein (LC-HF-NP, 2.2/78.7/19.1, and a high fat diet with carbohydrates ("high fat", 19.4/61.9/18.7. RESULTS: Body weight gain was reduced in all pair-fed experimental groups as compared to rats fed the control diet, with more pronounced effect in rats on LC-HF diets than on the high fat diet with carbohydrates. High fat diets increased expression of PGC1α and ADRB3 in BAT indicating higher SNS outflow. However, UCP1 mRNA expression and expression of UCP1 assessed by immunohistochemistry was not different between diet groups. In accordance, analysis of mitochondrial function in-vitro by extracellular flux analyser (Seahorse Bioscience and measurement of inducible thermogenesis in vivo (primary endpoint, explored by indirect calorimetry following norepinephrine injection, did not show significant differences between groups. Histology of BAT revealed increased lipid droplet size in rats fed the high-fat diet and both LC-HF diets. CONCLUSION: All experimental diets upregulated expression of genes which are indicative for increased BAT activity. However, the functional measurements in vivo revealed no increase of inducible BAT thermogenesis. This indicates that lower body weight gain with LC-HF diets and a high fat diet in a pair-feeding setting is not caused by

  11. Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue.

    Directory of Open Access Journals (Sweden)

    Elin Lundström

    Full Text Available To evaluate whether a water-fat magnetic resonance imaging (MRI cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT depot after a three-hour long mild cold exposure.Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related or altered absolute water content (perfusion-related.sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021 whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314. sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051 and SAT-R2* increased (mean = 0.40 s-1, P = 0.038 after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure.The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.

  12. Mechanisms and effective control of physiological browning phenomena in plant cell cultures.

    Science.gov (United States)

    Dong, Yan-Shan; Fu, Chun-Hua; Su, Peng; Xu, Xiang-Ping; Yuan, Jie; Wang, Sheng; Zhang, Meng; Zhao, Chun-Fang; Yu, Long-Jiang

    2016-01-01

    Browning phenomena are ubiquitous in plant cell cultures that severely hamper scientific research and widespread application of plant cell cultures. Up to now, this problem still has not been well controlled due to the unclear browning mechanisms in plant cell cultures. In this paper, the mechanisms were investigated using two typical materials with severe browning phenomena, Taxus chinensis and Glycyrrhiza inflata cells. Our results illustrated that the browning is attributed to a physiological enzymatic reaction, and phenolic biosynthesis regulated by sugar plays a decisive role in the browning. Furthermore, to confirm the specific compounds which participate in the enzymatic browning reaction, transcriptional profile and metabolites of T. chinensis cells, and UV scanning and high-performance liquid chromatography-mass spectrometry (HPLC-MS) profile of the browning compounds extracted from the brown-turned medium were analyzed, flavonoids derived from phenylpropanoid pathway were found to be the main compounds, and myricetin and quercetin were deduced to be the main substrates of the browning reaction. Inhibition of flavonoid biosynthesis can prevent the browning occurrence, and the browning is effectively controlled via blocking flavonoid biosynthesis by gibberellic acid (GA3 ) as an inhibitor, which further confirms that flavonoids mainly contribute to the browning. On the basis above, a model elucidating enzymatic browning mechanisms in plant cell cultures was put forward, and effective control approaches were presented.

  13. Biodegradable polymeric microsphere-based drug delivery for inductive browning of fat

    Directory of Open Access Journals (Sweden)

    Chunhui eJiang

    2015-11-01

    Full Text Available Brown and beige adipocytes are potent therapeutic agents to increase energy expenditure and reduce risks of obesity and its affiliated metabolic symptoms. One strategy to increase beige adipocyte content is through inhibition of the evolutionarily conserved Notch signaling pathway. However, systemic delivery of Notch inhibitors is associated with off-target effects and multiple dosages of application further faces technical and translational challenges. Here, we report the development of a biodegradable polymeric microsphere-based drug delivery system for sustained, local release of a Notch inhibitor, DBZ. The microsphere-based delivery system was fabricated and optimized using an emulsion/solvent evaporation technique to encapsulate DBZ into poly(lactide-co-glycolide (PLGA, a commonly used biodegradable polymer for controlled drug release. Release studies revealed the ability of PLGA microspheres to release DBZ in a sustained manner. Co-culture of white adipocytes with and without DBZ-loaded PLGA microspheres demonstrated that the released DBZ retained its bioactivity, and effectively inhibited Notch and promoted browning of white adipocytes. Injection of these DBZ-loaded PLGA microspheres into mouse inguinal white adipose tissue (WAT depots resulted in browning in vivo. Our results provide the encouraging proof-of-principle evidence for the application of biodegradable polymers as a controlled release platform for delivery of browning factors, and pave the way for development of new translational therapeutic strategies for treatment of obesity.

  14. Efficient Isolation of Cardiac Stem Cells from Brown Adipose

    Directory of Open Access Journals (Sweden)

    Zhiqiang Liu

    2010-01-01

    Full Text Available Cardiac stem cells represent a logical cell type to exploit in cardiac regeneration. The efficient harvest of cardiac stem cells from a suitable source would turn promising in cardiac stem cell therapy. Brown adipose was recently found to be a new source of cardiac stem cells, instrumental to myocardial regeneration. Unfortunately, an efficient method for the cell isolation is unavailable so far. In our study we have developed a new method for the efficient isolation of cardiac stem cells from brown adipose by combining different enzymes. Results showed that the total cell yield dramatically increased (more than 10 times, P<.01 compared with that by previous method. The content of CD133-positive cells (reported to differentiate into cardiomyocytes with a high frequency was much higher than that in the previous report (22.43% versus 3.5%. Moreover, the isolated cells could be the efficiently differentiated into functional cardiomyocytes in optimized conditions. Thus, the new method we established would be of great use in further exploring cardiac stem cell therapy.

  15. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone

    Science.gov (United States)

    Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (03); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and th...

  16. A high-fat diet impairs cooling-evoked brown adipose tissue activation via a vagal afferent mechanism.

    Science.gov (United States)

    Madden, Christopher J; Morrison, Shaun F

    2016-08-01

    In dramatic contrast to rats on a control diet, rats maintained on a high-fat diet (HFD) failed to activate brown adipose tissue (BAT) during cooling despite robust increases in their BAT activity following direct activation of their BAT sympathetic premotor neurons in the raphe pallidus. Cervical vagotomy or blockade of glutamate receptors in the nucleus of the tractus solitarii (NTS) reversed the HFD-induced inhibition of cold-evoked BAT activity. Thus, a HFD does not prevent rats from mounting a robust, centrally driven BAT thermogenesis; however, a HFD does alter a vagal afferent input to NTS neurons, thereby preventing the normal activation of BAT thermogenesis to cooling. These results, paralleling the absence of cooling-evoked glucose uptake in the BAT of obese humans, reveal a neural mechanism through which consumption of a HFD contributes to reduced energy expenditure and thus to weight gain. PMID:27354235

  17. Lithium and methylphenidate: opposite effects on perirenal brown fat Lítio e metilfenidato: efeitos opostos sobre a gordura perirrenal

    Directory of Open Access Journals (Sweden)

    José Menna Oliveira

    2010-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of the administration of lithium to adult rats on brown (perirenal and white (inguinal adipose tissues and to assess whether methylphenidate modulates lithium effects. METHODS: Twenty-five adult male Wistar rats were fed with either regular or lithium-containing chow for 30 days. Between days 15 to 30 of treatment, animals received daily intraperitoneal administrations of either methylphenidate or saline. RESULTS: Lithium significantly reduced perirenal fat, and this effect was minimized by the administration of methylphenidate. There were no significant differences between the groups in terms of the effects of lithium on inguinal fat. CONCLUSION: Our findings suggest that different effects on white and brown tissue distribution may be involved in lithium-induced weight gain.OBJETIVO: Avaliar como a administração de lítio afeta o tecido adiposo marrom (perirrenal e branco (inguinal e se o metilfenidato modula os efeitos do lítio. MÉTODOS: Vinte e cinco ratos Wistar adultos machos foram alimentados com ração normal ou contendo lítio por 30 dias. Entre os dias 15 e 30 de tratamento, os animais receberam doses intraperitoneais diárias de metilfenidato ou solução salina. RESULTADOS: A administração de lítio reduziu significativamente a gordura perirrenal. Esse efeito foi reduzido com a administração de metilfenidato. Não houve diferenças significativas entre os grupos em relação à gordura inguinal. CONCLUSÃO: Os achados sugerem que efeitos diferenciados sobre os tecidos adiposos marrom e branco podem estar envolvidos no ganho de peso induzido pelo tratamento com lítio.

  18. Shc depletion stimulates brown fat activity in vivo and in vitro

    OpenAIRE

    Tomilov, Alexey; Bettaieb, Ahmed; Kim, Kyoungmi; Sahdeo, Sunil; Tomilova, Natalia; Lam, Adam; Hagopian, Kevork; Connell, Michelle; Fong, Jennifer; Rowland, Douglas; Griffey, Stephen; Ramsey, Jon; Haj, Fawaz; Cortopassi, Gino

    2014-01-01

    Adipose tissue is an important metabolic organ that integrates a wide array of homeostatic processes and is crucial for whole-body insulin sensitivity and energy metabolism. Brown adipose tissue (BAT) is a key thermogenic tissue with a well-established role in energy expenditure. BAT dissipates energy and protects against both hypothermia and obesity. Thus, BAT stimulation therapy is a rational strategy for the looming pandemic of obesity, whose consequences and comorbidities have a huge impa...

  19. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat

    DEFF Research Database (Denmark)

    Teperino, Raffaele; Amann, Sabine; Bayer, Martina;

    2012-01-01

    Diabetes, obesity, and cancer affect upward of 15% of the world's population. Interestingly, all three diseases juxtapose dysregulated intracellular signaling with altered metabolic state. Exactly which genetic factors define stable metabolic set points in vivo remains poorly understood. Here, we......-independent glucose uptake in muscle and brown adipose tissue. These data identify multiple noncanonical endpoints that are pivotal for rational design of hedgehog modulators and provide a new therapeutic avenue for obesity and diabetes....

  20. Marrow fat cell: response to x-ray induced aplasia

    International Nuclear Information System (INIS)

    Adipose tissue is an integral structural component of normal rabbit marrow and is believed to behave primarily as a cushion in response to hemopoietic proliferation, accommodating to changes in hemopoiesis by change in either size or number or both of the fat cells in order to maintain constancy of the marrow volume. To test this hypothesis, aplasia of the right femur of New Zealand white rabbits was induced by x irradiation with 8000 rads; the left unirradiated limb served as control. Twenty-four hours before sacrifice 50 μCi of palmitate-114C was administered intravenously and the marrow of both femurs removed. Samples of perinephric fat were taken for comparison. Fat cell volume, C14 palmitate turnover and fatty acid composition were determined. The total number of fat cells in the entire marrow of both femurs was calculated. The measurements showed no difference in size or fatty acid turnover of the fat cells in the irradiated aplastic marrow from the cells of the control marrow. The number of fat cells in both the irradiated and the unirradiated control femurs was essentially the same. These findings do not support the view that marrow fat cells respond to diminished hematopoiesis by either increase in their volume or number. In addition, the findings suggest that both marrow and subcutaneous fat cells are fairly resistant to high doses of x-ray irradiation

  1. Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice

    Science.gov (United States)

    Liang, Xingwei; Yang, Qiyuan; Zhang, Lupei; Maricelli, Joseph W; Rodgers, Buel D.; Zhu, Mei-Jun; Du, Min

    2016-01-01

    Maternal obesity and high-fat diet (HFD) predisposes offspring to obesity and metabolic diseases. Due to uncoupling, brown adipose tissue (BAT) dissipates energy via heat generation, mitigating obesity and diabetes. The lactation stage is a manageable period for improving the health of offspring of obese mothers, but the impact of maternal HFD during lactation on offspring BAT function is unknown. To determine, female mice were fed either a control or HFD during lactation. At weaning, HFD offspring gained more body weight and had greater body fat mass compared to the control, and these differences maintained into adulthood, which correlated with glucose intolerance and insulin resistance in HFD offspring. Adaptive thermogenesis of BAT was impaired in HFD offspring at weaning. In adulthood, HFD offspring BAT had lower Ucp1 expression and thermogenic activity. Mechanistically, maternal HFD feeding during lactation elevated peripheral serotonin, which decreased the sensitivity of BAT to sympathetic β3-adrenergic signaling. Importantly, early postnatal metformin administration decreased serotonin concentration and ameliorated the impairment of offspring BAT due to maternal HFD. Our data suggest that attenuation of BAT thermogenic function may be a key mechanism linking maternal HFD during lactation to persisted metabolic disorder in the offspring. PMID:27686741

  2. 吡格列酮对小鼠皮下、内脏脂肪棕色化的差异作用%The different roles of Pioglitazone in fat browning

    Institute of Scientific and Technical Information of China (English)

    李玉洁; 刘娟; 毕建华; 丁国宪

    2013-01-01

    目的:探讨吡格列酮对小鼠皮下、内脏脂肪棕色化不同作用及其机制.方法:取C57BL/5J小鼠皮下及内脏前脂肪细胞原代培养,诱导分化同时加吡格列酮刺激直至分化成熟后,RT-PCR检测棕色脂肪相关功能基因的mRNA表达水平.结果:在皮下脂肪中吡格列酮组较对照组棕色脂肪功能基因均明显表达上调(P< 0.05),而内脏脂肪对照组和吡格列酮组差异无统计学意义(P>0.05).结论:吡格列酮可促进小鼠皮下脂肪棕色化改变,但对内脏脂肪无作用.%Objective:To explore the role of Pioglitazone in the browning of both subcutaneous and visceral adipose tissue.Methods:Primary subcutaneous and visceral adipocytes were isolated from C57BL/5J mice and induced for differentiation.The primary cells were stimulated with 2.5 μmol/L Pioglitazone or vehicle throughout the whole induction period.Then the expression of either white fat or brown fat relative genes were observed by RT-PCR.Results:Pioglitazone could cause a significant increase of brown fat marker genes in the subcutaneous adipose tissue instead of the visceral adipose.Conclusion:Pioglitazone can promote a "white to brown" change in the subcutaneous adipose tissue instead of the visceral adipose.

  3. Disruption of insulin signaling in Myf5-expressing progenitors leads to marked paucity of brown fat but normal muscle development.

    Science.gov (United States)

    Lynes, Matthew D; Schulz, Tim J; Pan, Andrew J; Tseng, Yu-Hua

    2015-05-01

    Insulin exerts pleiotropic effects on cell growth, survival, and metabolism, and its role in multiple tissues has been dissected using conditional knockout mice; however, its role in development has not been studied. Lineage tracing experiments have demonstrated that interscapular brown adipose tissue (BAT) arises from a Myf5-positive lineage shared with skeletal muscle and distinct from the majority of white adipose tissue (WAT) precursors. In this study, we sought to investigate the effects of impaired insulin signaling in the Myf5-expressing precursor cells by deleting the insulin receptor gene. Mice lacking insulin receptor in the Myf5 lineage (Myf5IRKO) have a decrease of interscapular BAT mass; however, muscle development appeared normal. Histologically, the residual BAT had decreased cell size but appeared mature and potentially functional. Expression of adipogenic inhibitors preadipocyte factor-1, Necdin, and wingless-type MMTV integration site member 10a in the residual BAT tissue was nonetheless increased compared with controls, and there was an enrichment of progenitor cells with impaired adipogenic differentiation capacity, suggesting a suppression of adipogenesis in BAT. Surprisingly, when cold challenged, Myf5IRKO mice did not show impaired thermogenesis. This resistance to cold could be attributed to an increased presence of uncoupling protein 1-positive brown adipocytes in sc WAT as well as increased expression of lipolytic activity in BAT. These data suggest a critical role of insulin signaling in the development of interscapular BAT from Myf5-positive progenitor cells, but it appears to be dispensable for muscle development. They also underscore the importance of compensatory browning of sc WAT in the absence of BAT for thermoregulation.

  4. Transplantation of Adipose Tissue and Adipose-Derived Stem Cells as a Tool to Study Metabolic Physiology and for Treatment of Disease

    OpenAIRE

    Tran, Thien T.; Kahn, C. Ronald

    2010-01-01

    Humans and other mammals have three main fat depots - visceral white fat, subcutaneous white fat, and brown fat - each possessing unique cell-autonomous properties. In contrast to visceral fat which can induce detrimental metabolic effects, subcutaneous white fat and brown fat have potential beneficial metabolic effects, including improved glucose homeostasis and increased energy consumption, which might be transferred by transplantation of these fat tissues. In addition, fat contains adipose...

  5. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced obesity.

    Science.gov (United States)

    Mwangi, Simon Musyoka; Nezami, Behtash Ghazi; Obukwelu, Blessing; Anitha, Mallappa; Marri, Smitha; Fu, Ping; Epperson, Monica F; Le, Ngoc-Anh; Shanmugam, Malathy; Sitaraman, Shanthi V; Tseng, Yu-Hua; Anania, Frank A; Srinivasan, Shanthi

    2014-03-01

    Obesity is a growing epidemic with limited effective treatments. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) was recently shown to enhance β-cell mass and improve glucose control in rodents. Its role in obesity is, however, not well characterized. In this study, we investigated the ability of GDNF to protect against high-fat diet (HFD)-induced obesity. GDNF transgenic (Tg) mice that overexpress GDNF under the control of the glial fibrillary acidic protein promoter and wild-type (WT) littermates were maintained on a HFD or regular rodent diet for 11 wk, and weight gain, energy expenditure, and insulin sensitivity were monitored. Differentiated mouse brown adipocytes and 3T3-L1 white adipocytes were used to study the effects of GDNF in vitro. Tg mice resisted the HFD-induced weight gain, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic steatosis seen in WT mice despite similar food intake and activity levels. They exhibited significantly (PGDNF enhanced β-adrenergic-mediated cAMP release in brown adipocytes and suppressed lipid accumulation in differentiated 3T3L-1 cells through a p38MAPK signaling pathway. Our studies demonstrate a novel role for GDNF in the regulation of high-fat diet-induced obesity through increased energy expenditure. They show that GDNF and its receptor agonists may be potential targets for the treatment or prevention of obesity.

  6. Dedifferentiated fat cells: A cell source for regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    Medet; Jumabay; Kristina; I; Bostr?m

    2015-01-01

    The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipidfree multipotent cells, referred to as dedifferentiated fat(DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.

  7. Comparative Study on the Hypoglycemic and Antioxidative Effects of Fermented Paste (Doenjang Prepared from Soybean and Brown Rice Mixed with Rice Bran or Red Ginseng Marc in Mice Fed with High Fat Diet

    Directory of Open Access Journals (Sweden)

    Soo Im Chung

    2014-10-01

    Full Text Available The effects of fermented paste made from soybean, brown rice, or brown rice in combination with rice bran or red ginseng marc on the glucose metabolism and antioxidative defense system in high fat-fed mice were investigated. The mice were given experimental diets for eight weeks: Normal control, high fat, and high fat supplemented with soybean fermented paste, brown rice fermented paste, brown rice-rice bran fermented paste, or brown rice-red ginseng marc fermented paste. The high fat group showed markedly higher blood glucose level and erythrocyte lipid peroxidation than the normal control group. Diet supplementation of fermented paste inhibited the high fat-induced hyperglycemia and oxidative stress via regulation of the glucose-regulating and antioxidant enzymes activities. The soybean and brown rice-red ginseng marc fermented pastes were the most effective in improving the glucose metabolism and antioxidant defense status in mice under high fat diet condition. These findings illustrate that brown rice, in combination with red ginseng marc, may be useful in the development of fermented paste with strong hypoglycemic and antioxidative activities.

  8. Numerical 3D modeling of heat transfer in human tissues for microwave radiometry monitoring of brown fat metabolism

    Science.gov (United States)

    Rodrigues, Dario B.; Maccarini, Paolo F.; Salahi, Sara; Colebeck, Erin; Topsakal, Erdem; Pereira, Pedro J. S.; Limão-Vieira, Paulo; Stauffer, Paul R.

    2013-02-01

    Background: Brown adipose tissue (BAT) plays an important role in whole body metabolism and could potentially mediate weight gain and insulin sensitivity. Although some imaging techniques allow BAT detection, there are currently no viable methods for continuous acquisition of BAT energy expenditure. We present a non-invasive technique for long term monitoring of BAT metabolism using microwave radiometry. Methods: A multilayer 3D computational model was created in HFSSTM with 1.5 mm skin, 3-10 mm subcutaneous fat, 200 mm muscle and a BAT region (2-6 cm3) located between fat and muscle. Based on this model, a log-spiral antenna was designed and optimized to maximize reception of thermal emissions from the target (BAT). The power absorption patterns calculated in HFSSTM were combined with simulated thermal distributions computed in COMSOL® to predict radiometric signal measured from an ultra-low-noise microwave radiometer. The power received by the antenna was characterized as a function of different levels of BAT metabolism under cold and noradrenergic stimulation. Results: The optimized frequency band was 1.5-2.2 GHz, with averaged antenna efficiency of 19%. The simulated power received by the radiometric antenna increased 2-9 mdBm (noradrenergic stimulus) and 4-15 mdBm (cold stimulus) corresponding to increased 15-fold BAT metabolism. Conclusions: Results demonstrated the ability to detect thermal radiation from small volumes (2-6 cm3) of BAT located up to 12 mm deep and to monitor small changes (0.5 °C) in BAT metabolism. As such, the developed miniature radiometric antenna sensor appears suitable for non-invasive long term monitoring of BAT metabolism.

  9. Activity of thyroxine 5' deiodinase in brown fat of lean and obese zucker rats

    International Nuclear Information System (INIS)

    This study examines the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for conversion of T4 to T3 in BAT, through activity of T4 5' deiodinase. Eighteen lean (Fa/.) and 18 age matched obese (fa/fa), about 16 weeks old, were each divided into 3 groups (n=6 per group). Group 1 and 2 were fed Purina Rat Chow and a cafeteria diet respectively for 21 days, and maintained at 220C+/-2. Group 3 was fed rat chow and maintained at 80C+/-1 for 7 days. Activity of T45'deiodinase was determined in vitro. T3 was measured by a radioimmunoassay. The rate of T4 to T3 conversion was similar in the lean and the obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet (about 40 to 50 pmol T3/scapular BAT depot, per hour). However, lean rats exposed to the cold displayed about a 5 fold increase in T45' deiodinase activity (p3 may account for the reduced tolerance of obese animals to cold, but it does not account for their reduced diet induced BAT thermogenesis

  10. Fatness

    DEFF Research Database (Denmark)

    Hansen, Anne Katrine Kleberg

    In 1727, the English physician Thomas Short wrote: “I believe no Age did ever afford more instances of Corpulency than our own.” Even in the 18th century, fatness was addressed as an issue of special contemporary concern. This thesis probes concepts and perceptions of fatness in Western European...... Medicine c. 1700–1900. It has been written with particular attention to whether and how fatness has been regarded as a disease during that period in history. One purpose of the thesis is to investigate the immediate period before fatness allegedly became problematized. Another purpose has been to grasp...

  11. Cold-increase in brown fat thyroxine 5'-monodeiodinase is attenuated in Zucker obese rat

    International Nuclear Information System (INIS)

    In this study the authors examined the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for enzymic conversion of thyroxine (T4) to triiodothyronine (T3) in BAT. A total of 34 lean and obese rats, ∼4 mo old were divided into three treatment groups: group 1 (5 lean and 6 obese) was fed Purina rat chow for 21 days, and group two (5 lean and 6 obese) was fed a cafeteria diet for 21 days, and groups 3 (6 lean and 6 obese) was fed Purina rat chow and maintained in the cold (8 +/- 10C) for 7 days. Activity of T4 5'-deiodinase was determined as the rate of T3 production from added T4 under controlled in vitro conditions. Serum T4 and T3 were determined by radioimmunoassay. The rate of T4-to-T3 conversion in BAT was similar in the lean and obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet. However, expressed per scapular BAT depot, lean rats exposed to cold displayed about a fivefold increase in BAT T3 production whereas only a small increase was observed in the cold-exposed obese rats. Serum T3 levels tended to be reduced in the Zucker obese rats. The data indicate a reduced capacity for T3 production of Zucker rat BAT exposed to cold. This defect may account for the reduced tolerance of the obese animals to cold, but it does not account for their reduced diet-induced BAT thermogenesis

  12. White and brown adipose stem cells: from signaling to clinical implications.

    Science.gov (United States)

    Algire, Carolyn; Medrikova, Dasa; Herzig, Stephan

    2013-05-01

    Epidemiological studies estimate that by the year 2030, 2.16 billion people worldwide will be overweight and 1.12 billion will be obese [1]. Besides its now established function as an endocrine organ, adipose tissue plays a fundamental role as an energy storage compartment. As such, adipose tissue is capable of extensive expansion or retraction depending on the energy balance or disease state of the host, a plasticity that is unparalleled in other organs and - under conditions of excessive energy intake - significantly contributes to the afore mentioned obesity pandemic. Expansion of adipose tissue is driven by both hypertrophy and hyperplasia of adipocytes, which can renew frequently to compensate for cell death. This underlines the importance of adipocyte progenitor cells within the distinct adipose tissue depots to control both energy storage and endocrine functions of adipose tissue. Here we summarize recent findings on the identity and plasticity of adipose stem cells, the involved signaling cascades, and potential clinical implications of these cells for the treatment of metabolic dysfunction in obesity. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  13. The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential Involvement of Brown and Beige/Brite Adipocyte Cell Lineages.

    Directory of Open Access Journals (Sweden)

    Rubén Cereijo

    Full Text Available Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area ("buffalo hump" has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from "buffalo hump" and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, non-fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-β-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e.g. UCP1 and, specifically, of "classical" brown adipocytes (e.g. ZIC1 but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-"classical brown adipocyte" phenotype

  14. Isolation of Precursor Cells from Waste Solid Fat Tissue

    Science.gov (United States)

    Byerly, Diane; Sognier, Marguerite A.

    2009-01-01

    A process for isolating tissue-specific progenitor cells exploits solid fat tissue obtained as waste from such elective surgical procedures as abdominoplasties (tummy tucks) and breast reductions. Until now, a painful and risky process of aspiration of bone marrow has been used to obtain a limited number of tissue- specific progenitor cells. The present process yields more tissue-specific progenitor cells and involves much less pain and risk for the patient. This process includes separation of fat from skin, mincing of the fat into small pieces, and forcing a fat saline mixture through a sieve. The mixture is then digested with collagenase type I in an incubator. After centrifugation tissue-specific progenitor cells are recovered and placed in a tissue-culture medium in flasks or Petri dishes. The tissue-specific progenitor cells can be used for such purposes as (1) generating three-dimensional tissue equivalent models for studying bone loss and muscle atrophy (among other deficiencies) and, ultimately, (2) generating replacements for tissues lost by the fat donor because of injury or disease.

  15. Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development

    Science.gov (United States)

    Although recent studies have shown that brown adipose tissue (BAT) arises from progenitor cells that also give rise to skeletal muscle, the developmental signals that control the formation of BAT remain largely unknown. Here, we show that brown preadipocytes possess primary cilia and can respond to ...

  16. Comparison of fatty acid, cholesterol, vitamin A and E composition, and trans fats in eggs from brown and white egg strains that were molted or nonmolted.

    Science.gov (United States)

    Anderson, Kenneth E

    2013-12-01

    The impact of egg color, hen strain, and molting on the nutritional composition of eggs is limited. Therefore, this study compared nutritional composition and component percentages of cage-produced shell eggs with respect to egg color, hen strain, and molt. Four strains were selected from the North Carolina Layer Performance and Management Test: Hy-Line Brown (HB) and Bovans Brown (BB), and Hy-Line W-36 (HW) and Bovans White (BovW) were selected. Two groups from each strain were selected and 2 groups of molted HW and BovW were selected and compared with their nonmolted counterparts to examine the molt's impact. Two sets of eggs from each replicate were collected simultaneously at 101 wk of age. One sample of eggs was broken into a 12-egg pool stomached for 3 min (n = 12 samples), then divided into six 50-mL tubes, sealed, and frozen to be sent for cholesterol, n-3 fatty acids, saturated fat, monounsaturated fats, polyunsaturated fats, β-carotene, vitamin A, and vitamin E analyses. The other set of 12 eggs was then assessed for component percentages. The HW eggs had a greater (P hens had a greater (P hens reduced (P hens. PMID:24235237

  17. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone.

    Science.gov (United States)

    Gordon, C J; Phillips, P M; Johnstone, A F M; Beasley, T E; Ledbetter, A D; Schladweiler, M C; Snow, S J; Kodavanti, U P

    2016-04-01

    Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (O3); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and then exposed to O3 (acute - air or 0.8 ppm O3 for 5 h, or subacute - air or 0.8 ppm O3 for 5 h/d 1 d/week for 4 weeks). Body composition was measured non-invasively using NMR. Ventilatory parameters and exploratory behavior were measured after the third week of subacute exposure. Bronchoalveolar lavage fluid (BALF) and blood chemistry data were collected 18 h after acute O3 and 18 h after the fourth week of subacute O3. The diets led to increased body fat in male but not female rats. O3-induced changes in ventilatory function were either unaffected or improved with the fructose and fat diets. O3-induced reduction in exploratory behavior was attenuated with fructose and fat diets in males and partially in females. O3 led to a significant decrease in body fat of males fed control diet but not the fructose or fat diet. O3 led to significant increases in BALF eosinophils, increase in albumin, and reductions in macrophages. Female rats appeared to be more affected than males to O3 regardless of diet. Overall, treatment with high-fructose and high-fat diets attenuated some O3 induced effects on pulmonary function, behavior, and metabolism. Exacerbation of toxicity was observed less frequently. PMID:27092583

  18. Pharmacological and nutritional agents promoting browning of white adipose tissue.

    Science.gov (United States)

    Bonet, M Luisa; Oliver, Paula; Palou, Andreu

    2013-05-01

    The role of brown adipose tissue in the regulation of energy balance and maintenance of body weight is well known in rodents. Recently, interest in this tissue has re-emerged due to the realization of active brown-like adipose tissue in adult humans and inducible brown-like adipocytes in white adipose tissue depots in response to appropriate stimuli ("browning process"). Brown-like adipocytes that appear in white fat depots have been called "brite" (from brown-in-white) or "beige" adipocytes and have characteristics similar to brown adipocytes, in particular the capacity for uncoupled respiration. There is controversy as to the origin of these brite/beige adipocytes, but regardless of this, induction of the browning of white fat represents an attractive potential strategy for the management and treatment of obesity and related complications. Here, the different physiological, pharmacological and dietary determinants that have been linked to white-to-brown fat remodeling and the molecular mechanisms involved are reviewed in detail. In the light of available data, interesting therapeutic perspectives can be expected from the use of specific drugs or food compounds able to induce a program of brown fat differentiation including uncoupling protein 1 expression and enhancing oxidative metabolism in white adipose cells. However, additional research is needed, mainly focused on the physiological relevance of browning and its dietary control, where the use of ferrets and other non-rodent animal models with a more similar adipose tissue organization and metabolism to humans could be of much help. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  19. Adsorption of phenolic compounds and browning products in white wines by yeasts and their cell walls.

    Science.gov (United States)

    Razmkhab, Sahar; Lopez-Toledano, Azahara; Ortega, José M; Mayen, Manuel; Merida, Julieta; Medina, Manuel

    2002-12-01

    Dehydrated yeast cells at variable concentrations were used as fining agents to decrease the color of white wines with two different degrees of browning (0.153 and 0.177 au, measured at 420 nm). Both wines showed a linear decrease of browning with increasing yeast concentration. However, in terms of efficiency, the yeasts exhibited a higher color lightening at greater concentrations acting on the darker wine. This suggests a preferential retention of some types of yellow-brown compounds that could increase their concentrations at the higher degree of browning. To confirm the role of yeast cell walls in the retention of browning compounds and to evaluate their potential use as fining agents, they were applied at variable concentrations to a browned wine (0.175 au). The cell walls were found to be the active support for the adsorption of browning compounds, but their efficiency was much lower than that of an equivalent amount of the yeast cells from which they were obtained. Finally, HPLC determinations of low-molecular-weight phenolic compounds showed flavan-3-ol derivatives to be significantly retained by both yeasts and their cell walls. PMID:12452671

  20. Intermittent cold exposure induces fat deposition in mice /

    OpenAIRE

    Yoo, Hyung sun

    2013-01-01

    Brown adipose tissue (BAT) is the most essential thermogenic organ in homeotherms. In mice, brown adipocytes like cells (beige adipocytes) appear in subcutaneous fat depot after prolonged cold exposure. Fully-functioning BAT and beige adipocytes in subcutaneous fat depot drive a sharp increase in energy expenditure. In fact, cold-elicited BAT activation and beige cell recruitment in subcutaneous adipose tissue have shown anti -obesity effect, making them a promising target for obesity treatme...

  1. Burning Fat Fuels Leukemic Stem Cell Heterogeneity.

    Science.gov (United States)

    Thomas, Daniel; Majeti, Ravindra

    2016-07-01

    Obese leukemia patients exhibit reduced survival after chemotherapy, suggesting an important role of adipose tissue in disease progression. In this issue of Cell Stem Cell, Ye et al. (2016) reveal metabolic heterogeneity in leukemic stem cell (LSC) subpopulations and show that chemotherapy-resistant CD36+ LSCs co-opt gonadal adipose tissue to support their metabolism and survival. PMID:27392217

  2. Surface antigenic profiling of stem cells from human omentum fat in comparison with subcutaneous fat and bone marrow

    OpenAIRE

    Dhanasekaran, M.; Indumathi, S.; Kanmani, A.; Poojitha, R.; Revathy, K. M.; Rajkumar, J. S.; D.Sudarsanam

    2012-01-01

    Omentum fat derived stem cells have emerged as an alternative and accessible therapeutic tool in recent years in contrast to the existing persuasive sources of stem cells, bone marrow and subcutaneous adipose tissue. However, there has been a scanty citation on human omentum fat derived stem cells. Furthermore, identification of specific cell surface markers among aforesaid sources is still controversial. In lieu of this existing perplexity, the current research work aims at signifying omentu...

  3. Dual Processing of FAT1 Cadherin Protein by Human Melanoma Cells Generates Distinct Protein Products*

    OpenAIRE

    Sadeqzadeh, Elham; de Bock, Charles E; Zhang, Xu Dong; Shipman, Kristy L.; Scott, Naomi M.; Song, Chaojun; Yeadon, Trina; Oliveira, Camila S.; Jin, Boquan; Hersey, Peter; Boyd, Andrew W.; Burns, Gordon F.; Thorne, Rick F.

    2011-01-01

    The giant cadherin FAT1 is one of four vertebrate orthologues of the Drosophila tumor suppressor fat. It engages in several functions, including cell polarity and migration, and in Hippo signaling during development. Homozygous deletions in oral cancer suggest that FAT1 may play a tumor suppressor role, although overexpression of FAT1 has been reported in some other cancers. Here we show using Northern blotting that human melanoma cell lines variably but universally express FAT1 and less comm...

  4. Breast reconstruction after nipple/areola-sparing mastectomy using cell-enhanced fat grafting

    OpenAIRE

    Calabrese C; Orzalesi L; Casella D.; Cataliotti L

    2009-01-01

    BACKGROUND: The success of fat grafting in breast reconstruction depends on fat retention. The use of stem-cells-enriched fat graft is an alternative method for graft stability. CASE REPORT: A case of nipple-areola sparing mastectomy double stage reconstruction with the use of stem cells enhanced fat graft is reported. CONCLUSIONS: Fat grafting is growing as a new and promising tool in reconstruction following nipple and areola sparing mastectomies as a way to restore a suffici...

  5. Exosomal microRNA miR-92a concentration in serum reflects human brown fat activity

    OpenAIRE

    Chen, Yong; Buyel, Joschka J.; Hanssen, Mark J. W.; Siegel, Franziska; Pan, Ruping; Naumann, Jennifer; Schell, Michael; van der Lans, Anouk; Schlein, Christian; Froehlich, Holger; Heeren, Joerg; Virtanen, Kirsi A.; van Marken Lichtenbelt, Wouter; Pfeifer, Alexander

    2016-01-01

    Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiation. To study BAT function in large human cohorts, novel diagnostic tools are needed. Here we show that brown adipocytes release exosomes and that BAT activation increases exosome release. Profiling m...

  6. Lower weight gain and hepatic lipid content in hamsters fed high fat diets supplemented with white rice protein, brown rice protein, soy protein, and their hydrolysates.

    Science.gov (United States)

    Zhang, Huijuan; Bartley, Glenn E; Mitchell, Cheryl R; Zhang, Hui; Yokoyama, Wallace

    2011-10-26

    The physiological effects of the hydrolysates of white rice protein (WRP), brown rice protein (BRP), and soy protein (SP) hydrolyzed by the food grade enzyme, alcalase2.4 L, were compared to the original protein source. Male Syrian Golden hamsters were fed high-fat diets containing either 20% casein (control) or 20% extracted proteins or their hydrolysates as the protein source for 3 weeks. The brown rice protein hydrolysate (BRPH) diet group reduced weight gain 76% compared with the control. Animals fed the BRPH supplemented diet also had lower final body weight, liver weight, very low density lipoprotein cholesterol (VLDL-C), and liver cholesterol, and higher fecal fat and bile acid excretion than the control. Expression levels of hepatic genes for lipid oxidation, PPARα, ACOX1, and CPT1, were highest for hamsters fed the BRPH supplemented diet. Expression of CYP7A1, the gene regulating bile acid synthesis, was higher in all test groups. Expression of CYP51, a gene coding for an enzyme involved in cholesterol synthesis, was highest in the BRPH diet group. The results suggest that BRPH includes unique peptides that reduce weight gain and hepatic cholesterol synthesis. PMID:21913675

  7. Prediction of milk, fat and protein yields in first lactation from serum ß-lactoglobulin concentrations during gestation in Italian Brown heifers

    Directory of Open Access Journals (Sweden)

    Paola Superchi

    2010-01-01

    Full Text Available The Authors report the results of a study carried out on 23 pregnant Italian Brown heifers, with the aim to determine the relationships between blood serum ß-lactoglobulin (ß-LG concentrations during first gestation and subsequent milk production and quality in first lactation, in order to obtain an improved selection method for replacement heifers. At weeks 20, 26 and 32 of gestation, ß-LG concentrations (±SE were 706±78, 753±66 and 772±63 ng/ml, respectively (P>0.05. High and significant (P≤0.05 correlation coefficients were observed only between ß-LG content at week 32 and total milk and protein yields in first lactation. Prediction equations of milk, fat and protein production in first lactation from log10 ß-LG content at week 32 of gestation, from parent average genetic indexes and from both were calculated by means of multiple regression analysis. When the contribution of both ß-LG content and predicted genetic indexes were considered, the regression equations gave generally a better estimate of the production parameters in first lactation (higher R2, lower SE of estimate than the above mentioned parameters alone. These results suggest that it is valuable to pre-estimate milk, fat and protein production in Italian Brown first lactating cows by means of the analysis of serum ß-LG content during gestation.

  8. The cell biology of fat expansion

    Science.gov (United States)

    Rutkowski, Joseph M.; Stern, Jennifer H.

    2015-01-01

    Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciphering adipocyte cell biology is an important component of understanding how the aberrant physiology of expanding adipose tissue contributes to the metabolic dysregulation associated with obesity. PMID:25733711

  9. Breathless cancer cells get fat on glutamine

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Anastasiou; Lewis C Cantley

    2012-01-01

    Many cancer cells depend on glutamine as a fuel for proliferation,yet the mechanisms by which glutamine supports cancer metabolism are not fully understood.Two recent studies highlight an important role for glutamine in the synthesis of lipids and provide novel insights into how glutamine metabolism could be targeted for cancer therapy.

  10. Small Buccal Fat Pad Cells Have High Osteogenic Differentiation Potential.

    Science.gov (United States)

    Tsurumachi, Niina; Akita, Daisuke; Kano, Koichiro; Matsumoto, Taro; Toriumi, Taku; Kazama, Tomohiko; Oki, Yoshinao; Tamura, Yoko; Tonogi, Morio; Isokawa, Keitaro; Shimizu, Noriyoshi; Honda, Masaki

    2016-03-01

    Dedifferentiated fat (DFAT) cells derived from mature adipocytes have mesenchymal stem cells' (MSCs) characteristics. Generally, mature adipocytes are 60-110 μm in diameter; however, association between adipocyte size and dedifferentiation efficiency is still unknown. This study, therefore, investigated the dedifferentiation efficiency of adipocytes based on cell diameter. Buccal fat pad was harvested from five human donors and dissociated by collagenase digestion. After exclusion of unwanted stromal cells by centrifugation, floating adipocytes were collected and their size distribution was analyzed. The floating adipocytes were then separated into two groups depending on cell size using 40- and 100-μm nylon mesh filters: cell diameters less than 40 μm (small adipocytes: S-adipocytes) and cell diameters of 40-100 μm (large adipocytes: L-adipocytes). Finally, we evaluated the efficiency of adipocyte dedifferentiation and then characterized the resultant DFAT cells. The S-adipocytes showed a higher capacity to dedifferentiate into DFAT cells (S-DFAT cells) compared to the L-adipocytes (L-DFAT cells). The S-DFAT cells also showed a relatively higher proportion of CD146-positive cells than L-DFAT cells, and exhibited more osteogenic differentiation ability based on the alkaline phosphatase activity and amount of calcium deposition. These results suggested that the S- and L-DFAT cells had distinct characteristics, and that the higher dedifferentiation potential of S-adipocytes compared to L-adipocytes gives the former group an advantage in yielding DFAT cells. PMID:26651216

  11. Mammalian Fat1 cadherin regulates actin dynamics and cell–cell contact

    OpenAIRE

    Tanoue, Takuji; Takeichi, Masatoshi

    2004-01-01

    Fat cadherins form a distinct subfamily of the cadherin gene superfamily, and are featured by their unusually large extracellular domain. In this work, we investigated the function of a mammalian Fat cadherin. Fat1 was localized at filopodial tips, lamellipodial edges, and cell–cell boundaries, overlapping with dynamic actin structures. RNA interference–mediated knockdown of Fat1 resulted in disorganization of cell junction–associated F-actin and other actin fibers/cables, disturbance of cell...

  12. The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals

    OpenAIRE

    Hou, Rong; Liu, Liming; Anees, Syed; Hiroyasu, Shungo; Sibinga, Nicholas E. S.

    2006-01-01

    The significance of cadherin superfamily proteins in vascular smooth muscle cell (VSMC) biology is undefined. Here we describe recent studies of the Fat1 protocadherin. Fat1 expression in VSMCs increases significantly after arterial injury or growth factor stimulation. Fat1 knockdown decreases VSMC migration in vitro, but surprisingly, enhances cyclin D1 expression and proliferation. Despite limited similarity to classical cadherins, the Fat1 intracellular domain (Fat1IC) interacts with β-cat...

  13. Spectroscopic, scanning laser OBIC, and I-V/QE characterizations of browned EVA solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Pern, F.J. [National Renewable Energy Lab., Golden, CO (United States); Eisgruber, I.L. [Materials Research Group, Inc., Wheat Ridge, CO (United States); Micheels, R.H. [Polestar Technologies, Inc., Needham Hts, MA (United States)

    1996-05-01

    The effects of ethylene-vinyl acetate (EVA) discoloration due to accelerated field or laboratory exposure on the encapsulated silicon (Si) solar cells or EVA/glass laminates were characterized quantitatively by using non-invasive, non-destructive ultraviolet-visible (UV-vis) spectrophotometry, spectrocolorimetry, spectrofluorometry, scanning laser OBIC (optical beam induced current) spectroscopy, and current-voltage (I-V) and quantum efficiency (QE) measurements. The results show that the yellowness index (YI) measured directly over the AR-coated solar cells under the glass superstrate increased from the range of -80 to -90 to the range of -20 to 15 as the EVA changed from clear to brown. The ratio of two fluorescence emission peak areas generally increased from 1.45 to 5.69 as browning increased, but dropped to 4.21 on a darker EVA. For a solar cell with brown EVA in the central region, small-area grating QE measurements and scanning laser OBIC analysis between the brown and clear EVA regions showed that the quantum efficiency loss at 633 nm was 42%-48% of the loss at 488 nm, due to a reduced decrease of transmittance in browned EVA at the longer wavelengths. The portion of the solar cell under the browned EVA showed a decrease of {approximately}36% in efficiency, as compared to the cell efficiency under clear EVA. Transmittance loss at 633 nm was 38% of the loss at 488 nm for a light yellow-brown EVA/glass laminate that showed a small increase of 10 in the yellowness index.

  14. Patterns of cell proliferation and cell death in the developing retina and optic tectum of the brown trout.

    NARCIS (Netherlands)

    Candal, E.; Anadon, R.; Grip, W.J. de; Rodriguez-Moldes, I.

    2005-01-01

    We have analyzed the patterns of cell proliferation and cell death in the retina and optic tectum of the brown trout (Salmo trutta fario) throughout embryonic and postembryonic stages. Cell proliferation was detected by immunohistochemistry with an antibody against the proliferating cell nuclear ant

  15. Mmp1 and Mmp2 cooperatively induce Drosophila fat body cell dissociation with distinct roles

    OpenAIRE

    Jia, Qiangqiang; Liu, Yang; Liu, Hanhan; Li, Sheng

    2014-01-01

    During Drosophila metamorphosis, the single-cell layer of fat body tissues gradually dissociates into individual cells. Via a fat body-specific RNAi screen in this study, we found that two matrix metalloproteinases (MMPs), Mmp1 and Mmp2, are both required for fat body cell dissociation. As revealed through a series of cellular, biochemical, molecular, and genetic experiments, Mmp1 preferentially cleaves DE-cadherin-mediated cell-cell junctions, while Mmp2 preferentially degrades basement memb...

  16. Patterns of brown fat uptake of 18F-fluorodeoxyglucose in positron emission tomography/computed tomography scan

    International Nuclear Information System (INIS)

    Fluorodeoxyglucose (FDG) positron emission tomography (PET) has become the common imaging modality in oncological practice. FDG uptake is seen in brown adipose tissue in a significant number of patients. Recognizing the uptake patterns is important for optimal FDG PET interpretation. The introduction of PET/computed tomography (PET/CT) revolutionized PET imaging, bringing much-needed anatomical information. Careful review and correlation of FDG PET images with anatomical imaging should be performed to characterize accurately any lesion having high FDG uptake

  17. Lithium and methylphenidate: opposite effects on perirenal brown fat Lítio e metilfenidato: efeitos opostos sobre a gordura perirrenal

    OpenAIRE

    José Menna Oliveira; Leonardo Machado Crema; Luísa Amália Diehl; Letícia Ferreira Pettenuzzo; Liane Tavares Bertinette; Carla Dalmaz; Elizabete Rocha da Rocha

    2010-01-01

    OBJECTIVE: To evaluate the effects of the administration of lithium to adult rats on brown (perirenal) and white (inguinal) adipose tissues and to assess whether methylphenidate modulates lithium effects. METHODS: Twenty-five adult male Wistar rats were fed with either regular or lithium-containing chow for 30 days. Between days 15 to 30 of treatment, animals received daily intraperitoneal administrations of either methylphenidate or saline. RESULTS: Lithium significantly reduced perirenal fa...

  18. MicroRNA Functions in Brite/Brown Fat — Novel Perspectives towards Anti-Obesity Strategies

    Directory of Open Access Journals (Sweden)

    Michael Karbiener

    2014-09-01

    Full Text Available Current anti-obesity strategies are aiming at restricting energy uptake, but still, obesity treatment is far from being satisfactory. The discovery of active brown adipose tissue (BAT in adult humans currently opens new avenues to combat obesity and follow-up complications as it tackles the other site of the energy balance: energy expenditure via non-shivering thermogenesis. This process of energy dissipation in the adipose tissue is tightly controlled, and the elucidation of its regulatory network is a key plank for therapeutic applications. MicroRNAs (miRNAs belong to a novel class of regulatory determinants which are small non-coding RNAs with vital roles in regulating gene expression that also play a role in many human diseases. In this review we summarize miRNAs which have been shown to govern thermogenic, i.e. brite or brown, adipocyte recruitment and physiology. Notably, most miRNAs in this context have so far been characterized solely in mice, revealing a great demand for more human studies. As in the context of other diseases, RNA-based therapeutics have meanwhile entered clinical trials, further exploring the functions of miRNAs in brown and white adipose tissues could result in novel therapeutic approaches to treat obesity and its follow-up complications.

  19. Brown spider venom toxins interact with cell surface and are endocytosed by rabbit endothelial cells.

    Science.gov (United States)

    Nowatzki, Jenifer; de Sene, Reginaldo Vieira; Paludo, Katia Sabrina; Veiga, Silvio Sanches; Oliver, Constance; Jamur, Maria Célia; Nader, Helena Bonciani; Trindade, Edvaldo S; Franco, Célia Regina C

    2010-09-15

    Bites from the Loxosceles genus (brown spiders) cause severe clinical symptoms, including dermonecrotic injury, hemorrhage, hemolysis, platelet aggregation and renal failure. Histological findings of dermonecrotic lesions in animals exposed to Loxosceles intermedia venom show numerous vascular alterations. Study of the hemorrhagic consequences of the venom in endothelial cells has demonstrated that the degeneration of blood vessels results not only from degradation of the extracellular matrix molecule or massive leukocyte infiltration, but also from a direct and primary activity of the venom on endothelial cells. Exposure of an endothelial cell line in vitro to L. intermedia venom induce morphological alterations, such as cell retraction and disadhesion to the extracellular matrix. The aim of the present study was to investigate the interaction between the venom toxins and the endothelial cell surface and their possible internalization, in order to illuminate the information about the deleterious effect triggered by venom. After treating endothelial cells with venom toxins, we observed that the venom interacts with cell surface. Venom treatment also can cause a reduction of cell surface glycoconjugates. When cells were permeabilized, it was possible to verify that some venom toxins were internalized by the endothelial cells. The venom internalization involves endocytic vesicles and the venom was detected in the lysosomes. However, no damage to lysosomal integrity was observed, suggesting that the cytotoxic effect evoked by L. intermedia venom on endothelial cells is not mediated by venom internalization.

  20. Aging and Regional Differences in Fat Cell Progenitors – A Mini-Review

    OpenAIRE

    Sepe, Anna; Tchkonia, Tamara; Thomou, Thomas; Zamboni, Mauro; Kirkland, James L.

    2010-01-01

    Fat mass and fat tissue distribution change dramatically throughout life. In old age, fat becomes dysfunctional and is redistributed from subcutaneous to intra-abdominal visceral depots as well as other ectopic sites, including bone marrow, muscle and the liver. These changes are associated with increased risk of metabolic syndrome. Fat tissue is a nutrient storage, endocrine and immune organ that undergoes renewal throughout the lifespan. Preadipocytes, which account for 15–50% of cells in f...

  1. Hypothesis: Cryptochromes and brown fat are essential for adaptation and affect mood and mood-related behaviors.

    Directory of Open Access Journals (Sweden)

    Timo ePartonen

    2012-11-01

    Full Text Available Solar radiation and ambient temperature have acted as selective physical forces among populations and thereby guided species distributions in the globe. Circadian clocks are universal and evolve when subjected to selection, and their properties contribute to variations in fitness within specific environments. Concerning humans, as compared to the remaining, the evening owls have a greater deviation from the 24-hour cycle, are under a greater pressure to circadian desynchrony and more prone to a cluster of health hazards with the increased mortality. Because of their position in the hierarchy and repressive actions, cryptochromes are the key components of the feedback loops on which circadian clocks are built. Based on the evidence a new hypothesis is formulated in which brown adipocytes with their cryptochromes are responsive to a broad range of physical stimuli from the habitat and through their activity ensure adaptation of the individual. The over-activated brown adipose tissue with deficient cryptochromes might induce disrupted thermoregulation and circadian desynchrony, and thereby contribute to lowered mood and pronounced depressive behaviors.

  2. Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice

    OpenAIRE

    Altintas, Mehmet M.; Azad, Adiba; Nayer, Behzad; Contreras, Gabriel; Zaias, Julia; Faul, Christian; Reiser, Jochen; Nayer, Ali

    2011-01-01

    Obesity is accompanied by adipocyte death and accumulation of macrophages and mast cells in expanding adipose tissues. Considering the differences in biological behavior of fat found in different anatomical locations, we explored the distribution of mast cells, solitary macrophages, and crown-like structures (CLS), the surrogates for dead adipocytes, in subcutaneous and abdominal visceral fat of lean and diet-induced obese C57BL/6 mice. In fat depots of lean mice, mast cells were far less pre...

  3. Brown adipocyte differentiation is regulated by hedgehog signaling during development

    Science.gov (United States)

    During development, brown fat tissue arises from mesenchymal precursor cells under the control of signaling networks that are not yet well understood. The Hedgehog (Hh) signaling pathway is one of the major signaling pathways that regulate mesenchymal cell fate. However, whether the Hh pathway contr...

  4. Regional variations in HDL metabolism in human fat cells: effect of cell size

    International Nuclear Information System (INIS)

    Abdominal obesity is related to reduced plasma high-density lipoprotein (HDL) cholesterol, and both are associated with cardiovascular disease risk. The authors have observed that plasma membranes from abdominal subcutaneous adipocytes have a greater HDL binding capacity than omental fat cell plasma membranes. The present study examined whether these binding characteristics could be due to differences in fat cell size or cholesterol concentration between the two adipose depots. Abdominal subcutaneous and deep omental fat were obtained from massively obese patients at surgery. Subcutaneous abdominal fat cells were significantly larger and their cellular cholesterol content greater than omental adipocytes. The uptake of HDL by collagenase-isolated fat cells was studied by incubating the cells for 2 h at 370C with 10 μg/ml 125I-HDL2 or 125I-HDL3. In both depots, the cellular uptake of 125I-HDL2 and 125I-HDL3 was specifically inhibited by addition of 25-fold excess unlabeled HDL and a close correlation was observed between the cellular uptake of 125I-HDL2 and 125I-HDL3. In obese patients, the uptake of 125I-HDL was higher in subcutaneous cells than in omental cells. The cellular 125I-HDL uptake was significantly correlated with adipocyte size and fat cell cholesterol content but not with adipocyte cholesterol concentration. These results suggest that the higher HDL uptake observed in subcutaneous cells compared with omental cells in obesity is the result of differences in adipocyte size rather than differences in the cholesterol concentration (cholesterol-to-triglyceride ratio). The increased interaction of HDL with hypertrophied abdominal adipocytes may play an important role in determining the lipid composition of HDL in obesity

  5. Regional variations in HDL metabolism in human fat cells: effect of cell size

    Energy Technology Data Exchange (ETDEWEB)

    Despres, J.; Fong, B.S.; Julien, P.; Jimenez, J.; Angel, A.

    1987-05-01

    Abdominal obesity is related to reduced plasma high-density lipoprotein (HDL) cholesterol, and both are associated with cardiovascular disease risk. The authors have observed that plasma membranes from abdominal subcutaneous adipocytes have a greater HDL binding capacity than omental fat cell plasma membranes. The present study examined whether these binding characteristics could be due to differences in fat cell size or cholesterol concentration between the two adipose depots. Abdominal subcutaneous and deep omental fat were obtained from massively obese patients at surgery. Subcutaneous abdominal fat cells were significantly larger and their cellular cholesterol content greater than omental adipocytes. The uptake of HDL by collagenase-isolated fat cells was studied by incubating the cells for 2 h at 37/sup 0/C with 10 ..mu..g/ml /sup 125/I-HDL/sub 2/ or /sup 125/I-HDL/sub 3/. In both depots, the cellular uptake of /sup 125/I-HDL/sub 2/ and /sup 125/I-HDL/sub 3/ was specifically inhibited by addition of 25-fold excess unlabeled HDL and a close correlation was observed between the cellular uptake of /sup 125/I-HDL/sub 2/ and /sup 125/I-HDL/sub 3/. In obese patients, the uptake of /sup 125/I-HDL was higher in subcutaneous cells than in omental cells. The cellular /sup 125/I-HDL uptake was significantly correlated with adipocyte size and fat cell cholesterol content but not with adipocyte cholesterol concentration. These results suggest that the higher HDL uptake observed in subcutaneous cells compared with omental cells in obesity is the result of differences in adipocyte size rather than differences in the cholesterol concentration (cholesterol-to-triglyceride ratio). The increased interaction of HDL with hypertrophied abdominal adipocytes may play an important role in determining the lipid composition of HDL in obesity.

  6. Derivation of epithelial-like cells from eyelid fat-derived stem cells in thermosensitive hydrogel.

    Science.gov (United States)

    Heidari Keshel, Saeed; Rostampour, Maryam; Khosropour, Golbahar; Bandbon B, Atefehsadat; Baradaran-Rafii, Alireza; Biazar, Esmaeil

    2016-01-01

    Injectable hydrogel is one of the great interests for tissue engineering and cell encapsulation. In the study, the thermosensitive chitosan/gelatin/β-glycerol phosphate (C/G/GP) disodium salt hydrogels were designed and investigated by different analyses. The eye fat-derived stem cells were used to evaluate the biocompatibility of hydrogels based on their phenotypic profile, viability, proliferation, and attachment ability. The results show that the sol/gel transition temperature of the C/G/GP hydrogel was in the range of 31.1-33.8 °C at neutral pH value, the gelation time was shortened, and the gel strength also improved at body temperature when compared with the C/GP hydrogel. In vitro cell culture experiments with eyelid fat-derived stem cells in hydrogel showed beneficial effects on the cell phenotypic morphology, proliferation, and differentiation. Microscopic figures showed that the eyelid fat stem cell were firmly anchored to the substrates and were able to retain a normal stem cell phenotype. Immunocytochemistry (ICC) and real-time-PCR results revealed change in the expression profile of eyelid fat stem cells grown with hydrogels when compared to those grown on control in epithelial induction condition. This study indicates that using chitosan/gelatin/β-glycerol phosphate hydrogel for cell culture is feasible and may apply in minimal invasive surgery in the future.

  7. Browning attenuates murine white adipose tissue expansion during postnatal development.

    Science.gov (United States)

    Lasar, D; Julius, A; Fromme, T; Klingenspor, M

    2013-05-01

    During postnatal development of mice distinct white adipose tissue depots display a transient appearance of brown-like adipocytes. These brite (brown in white) adipocytes share characteristics with classical brown adipocytes including a multilocular appearance and the expression of the thermogenic protein uncoupling protein 1. In this study, we compared two inbred mouse strains 129S6sv/ev and C57BL6/N known for their different propensity to diet-induced obesity. We observed transient browning in retroperitoneal and inguinal adipose tissue depots of these two strains. From postnatal day 10 to 20 the increase in the abundance of multilocular adipocytes and uncoupling protein 1 expression was higher in 129S6sv/ev than in C57BL6/N pups. The parallel increase in the mass of the two fat depots was attenuated during this browning period. Conversely, epididymal white and interscapular brown adipose tissue displayed a steady increase in mass during the first 30 days of life. In this period, 129S6sv/ev mice developed a significantly higher total body fat mass than C57BL6/N. Thus, while on a local depot level a high number of brite cells is associated with the attenuation of adipose tissue expansion the strain comparison reveals no support for a systemic impact on energy balance. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  8. Importance of mesenchymal stem cells in autologous fat grafting

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter Viktor;

    2012-01-01

    Autologous fat grafting (lipofilling) enables repair and augmentation of soft tissues and is increasingly used both in aesthetic and reconstructive surgery. Autologous fat has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main...

  9. Effect of diglycine mutant FAT10 on the proliferation and apoptosis of cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Cui LI

    2015-01-01

    Full Text Available Objective To investigate the effects of FAT10ΔGG, a carboxyl-terminal diglycine deficient mutant, on the proliferation and apoptosis of cervical cancer cell line HeLa. Methods Specimens of cervical carcinoma in situ and normal cervix tissue, 5 each, were collected. The expressive levels of FAT10 protein in these specimens were detected by Western blotting. Sitedirected mutagenesis was applied to construct the mutant pcDNA3.0-flag-FAT10ΔGG plasmid. The HeLa cells were then transiently transfected with wild-type FAT10, FAT10ΔGG and empty vector (used as negative control, and the wild-type HeLa cells served as blank control. The transfection efficiency of FAT10 or FAT10ΔGG was detected by Western blotting, and cell proliferation was determined by CCK-8 assay. Cisplatin was used to induce cell apoptosis after cells were transfected for 24h, and the cell apoptotic rates of all groups were determined by flow cytometry. Results Western blotting showed a significantly increased expression of FAT10 protein in cervical carcinoma tissues compared with that in normal cervical tissue. Over-expression of wild FAT10 in HeLa cells obviously promoted cell proliferation, but this promotion was significantly inhibited in cells transfected with its diglycine mutant. Compared with blank control group (22.7%±4.2% and negative control group (24.1%±3.8%, the apoptotic rate was significantly reduced in wild FAT10 group (10.9%±2.0%, P0.05. Conclusion FAT10 can promote cell proliferation and inhibit cell apoptosis through its carboxyl-terminal diglycine motif, and it may play an essential role in carcinogenesis and development of cancer. DOI: 10.11855/j.issn.0577-7402.2014.12.01

  10. Genome-wide mapping of Quantitative Trait Loci for fatness, fat cell characteristics and fat metabolism in three porcine F2 crosses

    Directory of Open Access Journals (Sweden)

    Bartenschlager Heinz

    2010-07-01

    Full Text Available Abstract Background QTL affecting fat deposition related performance traits have been considered in several studies and mapped on numerous porcine chromosomes. However, activity of specific enzymes, protein content and cell structure in fat tissue probably depend on a smaller number of genes than traits related to fat content in carcass. Thus, in this work traits related to metabolic and cytological features of back fat tissue and fat related performance traits were investigated in a genome-wide QTL analysis. QTL similarities and differences were examined between three F2 crosses, and between male and female animals. Methods A total of 966 F2 animals originating from crosses between Meishan (M, Pietrain (P and European wild boar (W were analysed for traits related to fat performance (11, enzymatic activity (9 and number and volume of fat cells (20. Per cross, 216 (M × P, 169 (W × P and 195 (W × M genome-wide distributed marker loci were genotyped. QTL mapping was performed separately for each cross in steps of 1 cM and steps were reduced when the distance between loci was shorter. The additive and dominant components of QTL positions were detected stepwise by using a multiple position model. Results A total of 147 genome-wide significant QTL (76 at P CAPN6. Additional genome-wide significant QTL were found on SSC8, 12, 13, 14, 16, and 18. In many cases, the QTL are mainly additive and differ between F2 crosses. Many of the QTL profiles possess multiple peaks especially in regions with a high marker density. Sex specific analyses, performed for example on SSC6, SSC7 and SSCX, show that for some traits the positions differ between male and female animals. For the selected traits, the additive and dominant components that were analysed for QTL positions on different chromosomes, explain in combination up to 23% of the total trait variance. Conclusions Our results reveal specific and partly new QTL positions across genetically diverse pig crosses

  11. FAT10, a gene up-regulated in various cancers, is cell-cycle regulated

    OpenAIRE

    Zhang Dongwei; Lim Chuan-Bian; Lee Caroline GL

    2006-01-01

    Abstract Background FAT10 is a member of the ubiquitin-like-modifier family of proteins. Over-expression of the FAT10 gene was observed in the tumors of several epithelial cancers. High FAT10 expression was found to lead to increased chromosome instability via the reduction in the kinetochore localization of MAD2 during the prometaphase stage of the cell-cycle. FAT10 expression was also previously reported to be regulated by cytokines and p53. Results Here, we report that FAT10 expression is ...

  12. Islet Cell Response to High Fat Programming in Neonate, Weanling and Adolescent Wistar Rats

    OpenAIRE

    Cerf, Marlon E.; Johan Louw

    2014-01-01

    Context High fat programming, by exposure to a high saturated fat diet during fetal and/or lactational life induces metabolic derangements and alters islet cell architecture in neonate and weanling rats. Objective The present study assessed metabolic hanges and islet cell dynamics in response to high fat maintenance during specific developmental periods in adolescent rats, with some parameters also studied in neonate and weanling rats. Methods The experimental groups comprised neonates, weanl...

  13. Lipid profile in eggs of Araucana hens compared with Lohmann Selected Leghorn and ISA Brown hens given diets with different fat sources.

    Science.gov (United States)

    Millet, S; De Ceulaer, K; Van Paemel, M; Raes, K; De Smet, S; Janssens, G P J

    2006-06-01

    1. In a cross-over trial, the egg cholesterol and fatty acid composition of Araucana hens was compared with those of two commercial breeds (Lohmann Selected Leghorn and ISA Brown) under two feeding regimes, either high (Hn-3) or low (Ln-3) in long-chain n-3 fatty acids. 2. The Hn-3 diet was formed by isocaloric substitution of animal fat in the control diet (Ln-3) by a dry product containing stabilised fish oil with standardised concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). 3. Both breed and diet had influences on egg composition, without interactions. 4. The Araucana breed showed lower feed intake and lower egg weights than the other two breeds. The yolk weight was similar, leading to a much higher yolk:albumen ratio in the Araucana eggs. 5. In comparison to commercial breeds, Araucanas produced eggs with higher cholesterol content per g of yolk, which was even more pronounced when expressed per g of egg, due to the high yolk content of the eggs. The cholesterol content of an egg remained unchanged by the diet, irrespective of the dietary fat source. 6. Changing to the Hn-3 diet led to greater concentrations of polyunsaturated fatty acids (PUFA) and lower concentrations of monounsaturated fatty acids (MUFA) contents in the yolk, without a change in the ratio of saturated (SFA) to unsaturated fatty acids (UFA). 7. Within the PUFA, the n-3 fatty acids increased at the expense of the n-6 fatty acids, indicating a competition between n-3 and n-6 fatty acids for incorporation in the yolk. PMID:16787853

  14. Brown algae overproduce cell wall polysaccharides as a protection mechanism against the heavy metal toxicity

    International Nuclear Information System (INIS)

    Brown algae are often used as heavy metal biomonitors and biosorbents because they can accumulate high concentrations of metals. Cation-exchange performed by cell wall polysaccharides is pointed out as the main chemical mechanism for the metal sequestration. Here, we biochemically investigated if the brown alga Padina gymnospora living in a heavy metal contaminated area would modify their polysaccharidic content. We exposed non-living biomass to Cd and Pb and studied the metals adsorption and localization. We found that raw dried polysaccharides, sulfate groups, uronic acids, fucose, mannose, and galactose were significantly higher in contaminated algae compared with the control ones. Metal concentrations adsorbed by non-living biomass were rising comparatively to the tested concentrations. Electron microscopy showed numerous granules in the cell walls and X-ray microanalysis revealed Cd as the main element. We concluded that P. gymnospora overproduces cell wall polysaccharides when exposed to high metal concentrations as a defense mechanism.

  15. Brown adipose tissue harbors a distinct sub-population of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Dasa Medrikova

    Full Text Available Regulatory T (Treg cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT. Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.

  16. Unilateral brown fat on [{sup 18}F]-F.D.G. PET/CT in the follow-up of a pleural mesothelioma; Detection unilaterale de graisse brune en [{sup 18}F]-FDG TEP/TDM dans le suivi d'un mesotheliome pleural

    Energy Technology Data Exchange (ETDEWEB)

    Waele, A. de; Deroose, C.M. [Katholieke Universiteit Leuven, Hopitaux Universitaires de Leuven, UZ Leuven, Dept. de Medecine Nucleaire, Leuven (Belgium); Nafteux, P. [Katholieke Universiteit Leuven, Hopitaux Universitaires de Leuven, Dept. de Chirurgie Thoracique, Leuven (Belgium); Nackaerts, K. [Katholieke Universiteit Leuven, Hopitaux Universitaires de Leuven, Dept. de Pneumologie, Leuven (Belgium)

    2009-10-15

    The fixation of the fluorodeoxyglucose (F.D.G.) in the brown fat is generally characterized by a strongly symmetric setting in some areas of predilection.Is reported here the case of a patient that after having undergone a multi modal treatment for a pleural mesothelioma presents a unilateral F.D.G. fixation in the brown fat, this fixation can be inhibited by the administering of a beta adrenergic blocking agent. (N.C.)

  17. Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

    Science.gov (United States)

    Suárez-Zamorano, Nicolas; Fabbiano, Salvatore; Chevalier, Claire; Stojanović, Ozren; Colin, Didier J; Stevanović, Ana; Veyrat-Durebex, Christelle; Tarallo, Valentina; Rigo, Dorothée; Germain, Stéphane; Ilievska, Miroslava; Montet, Xavier; Seimbille, Yann; Hapfelmeier, Siegfried; Trajkovski, Mirko

    2015-12-01

    Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

  18. Frequent extreme cold exposure and brown fat and cold-induced thermogenesis: a study in a monozygotic twin.

    Directory of Open Access Journals (Sweden)

    Maarten J Vosselman

    Full Text Available INTRODUCTION: Mild cold acclimation is known to increase brown adipose tissue (BAT activity and cold-induced thermogenesis (CIT in humans. We here tested the effect of a lifestyle with frequent exposure to extreme cold on BAT and CIT in a Dutch man known as 'the Iceman', who has multiple world records in withstanding extreme cold challenges. Furthermore, his monozygotic twin brother who has a 'normal' sedentary lifestyle without extreme cold exposures was measured. METHODS: The Iceman (subject A and his brother (subject B were studied during mild cold (13°C and thermoneutral conditions (31°C. Measurements included BAT activity and respiratory muscle activity by [18F]FDG-PET/CT imaging and energy expenditure through indirect calorimetry. In addition, body temperatures, cardiovascular parameters, skin perfusion, and thermal sensation and comfort were measured. Finally, we determined polymorphisms for uncoupling protein-1 and β3-adrenergic receptor. RESULTS: Subjects had comparable BAT activity (A: 1144 SUVtotal and B: 1325 SUVtotal, within the range previously observed in young adult men. They were genotyped with the polymorphism for uncoupling protein-1 (G/G. CIT was relatively high (A: 40.1% and B: 41.9%, but unlike during our previous cold exposure tests in young adult men, here both subjects practiced a g-Tummo like breathing technique, which involves vigorous respiratory muscle activity. This was confirmed by high [18F]FDG-uptake in respiratory muscle. CONCLUSION: No significant differences were found between the two subjects, indicating that a lifestyle with frequent exposures to extreme cold does not seem to affect BAT activity and CIT. In both subjects, BAT was not higher compared to earlier observations, whereas CIT was very high, suggesting that g-Tummo like breathing during cold exposure may cause additional heat production by vigorous isometric respiratory muscle contraction. The results must be interpreted with caution given the

  19. Atrophin Proteins Interact with the Fat1 Cadherin and Regulate Migration and Orientation in Vascular Smooth Muscle Cells*S⃞

    OpenAIRE

    Hou, Rong; Sibinga, Nicholas E. S.

    2009-01-01

    Fat1, an atypical cadherin induced robustly after arterial injury, has significant effects on mammalian vascular smooth muscle cell (VSMC) growth and migration. The related Drosophila protein Fat interacts genetically and physically with Atrophin, a protein essential for development and control of cell polarity. We hypothesized that interactions between Fat1 and mammalian Atrophin (Atr) proteins might contribute to Fat1 effects on VSMCs. Like Fat1, mammalian Atr expres...

  20. Candidate gene association analysis for milk yield, composition, urea nitrogen and somatic cell scores in Brown Swiss cows.

    Science.gov (United States)

    Cecchinato, A; Ribeca, C; Chessa, S; Cipolat-Gotet, C; Maretto, F; Casellas, J; Bittante, G

    2014-07-01

    The aim of this study was to investigate 96 single-nucleotide polymorphisms (SNPs) from 54 candidate genes, and test the associations of the polymorphic SNPs with milk yield, composition, milk urea nitrogen (MUN) content and somatic cell score (SCS) in individual milk samples from Italian Brown Swiss cows. Milk and blood samples were collected from 1271 cows sampled once from 85 herds. Milk production, quality traits (i.e. protein, casein, fat and lactose percentages), MUN and SCS were measured for each milk sample. Genotyping was performed using a custom Illumina VeraCode GoldenGate approach. A Bayesian linear animal model that considered the effects of herd, days in milk, parity, SNP genotype and additive polygenic effect was used for the association analysis. Our results showed that 14 of the 51 polymorphic SNPs had relevant additive effects on at least one of the aforementioned traits. Polymorphisms in the glucocorticoid receptor DNA-binding factor 1 (GRLF1), prolactin receptor (PRLR) and chemokine ligand 2 (CCL2) were associated with milk yield; an SNP in the stearoyl-CoA desaturase (SCD-1) was related to fat content; SNPs in the caspase recruitment domain 15 protein (CARD15) and lipin 1 (LPIN1) affected the protein and casein contents; SNPs in growth hormone 1 (GH1), lactotransferrin (LTF) and SCD-1 were relevant for casein number; variants in beta casein (CSN2), GH1, GRLF1 and LTF affected lactose content; SNPs in beta-2 adrenergic receptor (ADRB2), serpin peptidase inhibitor (PI) and SCD-1 were associated with MUN; and SNPs in acetyl-CoA carboxylase alpha (ACACA) and signal transducer and activator of transcription 5A (STAT5A) were relevant in explaining the variation of SCS. Although further research is needed to validate these SNPs in other populations and breeds, the association between these markers and milk yield, composition, MUN and SCS could be exploited in gene-assisted selection programs for genetic improvement purposes.

  1. Candidate gene association analysis for milk yield, composition, urea nitrogen and somatic cell scores in Brown Swiss cows.

    Science.gov (United States)

    Cecchinato, A; Ribeca, C; Chessa, S; Cipolat-Gotet, C; Maretto, F; Casellas, J; Bittante, G

    2014-07-01

    The aim of this study was to investigate 96 single-nucleotide polymorphisms (SNPs) from 54 candidate genes, and test the associations of the polymorphic SNPs with milk yield, composition, milk urea nitrogen (MUN) content and somatic cell score (SCS) in individual milk samples from Italian Brown Swiss cows. Milk and blood samples were collected from 1271 cows sampled once from 85 herds. Milk production, quality traits (i.e. protein, casein, fat and lactose percentages), MUN and SCS were measured for each milk sample. Genotyping was performed using a custom Illumina VeraCode GoldenGate approach. A Bayesian linear animal model that considered the effects of herd, days in milk, parity, SNP genotype and additive polygenic effect was used for the association analysis. Our results showed that 14 of the 51 polymorphic SNPs had relevant additive effects on at least one of the aforementioned traits. Polymorphisms in the glucocorticoid receptor DNA-binding factor 1 (GRLF1), prolactin receptor (PRLR) and chemokine ligand 2 (CCL2) were associated with milk yield; an SNP in the stearoyl-CoA desaturase (SCD-1) was related to fat content; SNPs in the caspase recruitment domain 15 protein (CARD15) and lipin 1 (LPIN1) affected the protein and casein contents; SNPs in growth hormone 1 (GH1), lactotransferrin (LTF) and SCD-1 were relevant for casein number; variants in beta casein (CSN2), GH1, GRLF1 and LTF affected lactose content; SNPs in beta-2 adrenergic receptor (ADRB2), serpin peptidase inhibitor (PI) and SCD-1 were associated with MUN; and SNPs in acetyl-CoA carboxylase alpha (ACACA) and signal transducer and activator of transcription 5A (STAT5A) were relevant in explaining the variation of SCS. Although further research is needed to validate these SNPs in other populations and breeds, the association between these markers and milk yield, composition, MUN and SCS could be exploited in gene-assisted selection programs for genetic improvement purposes. PMID:24804775

  2. β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-oxidation and is Inversely Correlated with Cardiometabolic Risk Factors

    Science.gov (United States)

    Roberts, Lee D.; Boström, Pontus; O’Sullivan, John F.; Schinzel, Robert T.; Lewis, Gregory D.; Dejam, Andre; Lee, Youn-Kyoung; Palma, Melinda J.; Calhoun, Sondra; Georgiadi, Anastasia; Chen, Ming-Huei; Ramachandran, Vasan S.; Larson, Martin G.; Bouchard, Claude; Rankinen, Tuomo; Souza, Amanda L.; Clish, Clary B.; Wang, Thomas J.; Estall, Jennifer L.; Soukas, Alexander A.; Cowan, Chad A.; Spiegelman, Bruce M.; Gerszten, Robert E.

    2014-01-01

    Summary The transcriptional co-activator peroxisome proliferator-activated receptor-gamma co-activator-1 α (PGC-1α) regulates metabolic genes in skeletal muscle, and contributes substantially to the response of muscle to exercise. Muscle specific PGC-1α transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1α mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolic profiling approach to examine metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a novel small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipose tissue and fatty acid β-oxidation in hepatocytes both in vitro and in vivo through a PPARα mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases. PMID:24411942

  3. Atypical Cadherin Fat1 Is Required for Lens Epithelial Cell Polarity and Proliferation but Not for Fiber Differentiation

    OpenAIRE

    Sugiyama, Yuki; Shelley, Elizabeth J.; Badouel, Caroline; McNeill, Helen; McAvoy, John W.

    2015-01-01

    Using knockout mice, we show that atypical cadherin Fat1 is essential for lens epithelial cells to maintain cell junctions, polarity, and proliferation but not for terminal fiber cell differentiation. We also report that Fat4 does not exhibit functional redundancy with Fat1 during lens development.

  4. MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

    DEFF Research Database (Denmark)

    Yin, Hang; Pasut, Alessandra; Soleimani, Vahab D;

    2013-01-01

    Brown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells...... (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3'UTR of Prdm16. Antagonism...... of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels...

  5. Role of Adipose-derived Stem Cells in Fat Grafting and Reconstructive Surgery

    Science.gov (United States)

    Tan, Shaun S; Ng, Zhi Yang; Zhan, Weiqing; Rozen, Warren

    2016-01-01

    Autologous fat grafting is commonly utilised to reconstruct soft tissue defects caused by ageing, trauma, chronic wounds and cancer resection. The benefits of fat grafting are minimal donor site morbidity and ease of availability through liposuction or lipectomy. Nonetheless, survival and longevity of fat grafts remain poor post-engraftment. Various methods to enhance fat graft survival are currently under investigation and its stem cell constituents are of particular interest. Cell-assisted lipotransfer refers to the addition of adipose-derived stem cell (ASC) rich component of stromal vascular fraction to lipoaspirate, the results of which have proven promising. This article aims to review the role of ASCs in fat grafting and reconstructive surgery.

  6. Hepatic fat is not associated with beta-cell function or postprandial free fatty acid response

    NARCIS (Netherlands)

    Rijkelijkhuizen, J.M.; Doesburg, T.; Girman, C.J.; Mari, A.; Rhodes, T.; Gastaldelli, A.; Nijpels, M.G.A.A.M.; Dekker, J.M.

    2009-01-01

    We evaluated the association of hepatic fat with beta-cell function estimated from the oral glucose tolerance test. In addition, we tested the hypothesis that postprandial free fatty acid (FFA) suppression after a meal tolerance test (MTT) is linked to hepatic fat. Individuals with normal glucose me

  7. Expression of the mitochondrial uncoupling protein in brown adipocytes. Absence in brown preadipocytes and BFC-1 cells. Modulation by isoproterenol in adipocytes.

    Science.gov (United States)

    Forest, C; Doglio, A; Casteilla, L; Ricquier, D; Ailhaud, G

    1987-01-01

    The expression of the uncoupling protein has been compared in cells of BFC-1 clonal line established from mouse brown adipose tissue (BAT) and in preadipocytes, as well as in adipocytes from mouse BAT, both in primary culture. The results of immunoblots show that, after one week in culture, adipocytes have a reduced level of the 32 kD protein. This level can be raised 2-3.5-fold by a 24-h exposure to isoproterenol. Thus a direct modulation by a beta-agonist drug in the expression of the uncoupling protein is observed. Under the same conditions as well as under various other conditions, preadipocytes in primary culture and BFC-1 cells do not express the uncoupling protein. At the same time these cells are able both to differentiate into adipose cells, as demonstrated by the emergence of enzyme markers and triglyceride accumulation, and to respond to isoproterenol. Thus isoproterenol is not sufficient to trigger the expression of the uncoupling protein and behaves as a mere modulator once the cells have acquired the capacity to express it. Injection of undifferentiated BFC-1 cells into athymic mice bearing catecholamine-containing mini-osmotic pumps, or co-cultures of BFC-1 cells and pheochromocytoma PC-12 cells do not allow BFC-1 cells to express the uncoupling protein. Taken together, the results suggest that the formation of brown preadipocytes is critically linked during development to the release by sympathetic nerves of specific trophic factors acting locally.

  8. The brown adipocyte differentiation pathway in birds: An evolutionary road not taken

    Directory of Open Access Journals (Sweden)

    Kumaratilake Jaliya S

    2008-04-01

    Full Text Available Abstract Background Thermogenic brown adipose tissue has never been described in birds or other non-mammalian vertebrates. Brown adipocytes in mammals are distinguished from the more common white fat adipocytes by having numerous small lipid droplets rather than a single large one, elevated numbers of mitochondria, and mitochondrial expression of the nuclear gene UCP1, the uncoupler of oxidative phosphorylation responsible for non-shivering thermogenesis. Results We have identified in vitro inductive conditions in which mesenchymal cells isolated from the embryonic chicken limb bud differentiate into avian brown adipocyte-like cells (ABALCs with the morphological and many of the biochemical properties of terminally differentiated brown adipocytes. Avian, and as we show here, lizard species lack the gene for UCP1, although it is present in amphibian and fish species. While ABALCs are therefore not functional brown adipocytes, they are generated by a developmental pathway virtually identical to brown fat differentiation in mammals: both the common adipogenic transcription factor peroxisome proliferator-activated receptor-γ (PPARγ, and a coactivator of that factor specific to brown fat differentiation in mammals, PGC1α, are elevated in expression, as are mitochondrial volume and DNA. Furthermore, ABALCs induction resulted in strong transcription from a transfected mouse UCP1 promoter. Conclusion These findings strongly suggest that the brown fat differentiation pathway evolved in a common ancestor of birds and mammals and its thermogenicity was lost in the avian lineage, with the degradation of UCP1, after it separated from the mammalian lineage. Since this event occurred no later than the saurian ancestor of birds and lizards, an implication of this is that dinosaurs had neither UCP1 nor canonically thermogenic brown fat.

  9. The influence of sexual hormones on lipogenesis and lipolysis in rat fat cells

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Fahmy, N; Nielsen, Jens Høiriis

    1980-01-01

    The insulin-stimulated conversion of glucose to fatty acids (fatty acid synthesis) and the maximally norepinephrine-stimulated lipolysis were studied in isolated fat cells from normal male and female rats, ovariectomized rats and sexual hormone-treated normal and ovariectomized rats. The fatty acid...... synthesis and the lipolysis oscillated considerably more in fat cells from female rats than in fat cells from male rats. This was found to be due to the oestrous cycle, since the fatty acid synthesis was high in prooestrus and low in both oestrus and dioestrus, while the lipolysis was higher in oestrus and...... prooestrus than in dioestrus. Oestradiol treatment of both female and male rats and testosterone treatment of male rats for three days lowered the fatty acid synthesis and increased the lipolysis. The metabolic oscillation disappeared in ovariectomized rats, and the fat cells from these animals showed a...

  10. Drosophila Ste-20 Family Protein Kinase, Hippo, Modulates Fat Cell Proliferation

    OpenAIRE

    Hongling Huang; Wenqing Wu; Lei Zhang; Xin-Yuan Liu

    2013-01-01

    BACKGROUND: Evolutionarily conserved Hippo (Hpo) pathway plays a pivotal role in the control of organ size. Although the Hpo pathway regulates proliferation of a variety of epidermal cells, its function in non-ectoderm-derived cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Through methods including fat quantification assays, starvation assays, in vivo labeling assays, we show that overexpression of Hpo in Drosophila melanogaster fat body restricts Drosophila body growth and reduces...

  11. Mammary fat of breast cancer: gene expression profiling and functional characterization.

    Directory of Open Access Journals (Sweden)

    Fengliang Wang

    Full Text Available Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies.

  12. Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

    Science.gov (United States)

    Perrot, Pierre; Rousseau, Julie; Bouffaut, Anne-Laure; Rédini, Françoise; Cassagnau, Elisabeth; Deschaseaux, Frédéric; Heymann, Marie-Françoise; Heymann, Dominique; Duteille, Franck; Trichet, Valérie; Gouin, François

    2010-01-01

    Background Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context. PMID:20544017

  13. Parametrial fat tissue from high fat diet-treated SKH-1 mice stimulates transformation of mouse epidermal JB6 cells

    OpenAIRE

    Bernard, Jamie J.; Lou, You-Rong; Peng, Qing-Yun; Li, Tao; Vakil, Priyal R.; Ding, Ning; Laskin, Jeffrey D.; Dong, Zigang; Conney, Allan H.; Lu, Yao-Ping

    2014-01-01

    Our previous studies indicated that decreasing visceral adipose tissue by surgical removal of the parametrial fat pads inhibited UVB-induced carcinogenesis in SKH-1 mice fed a high fat diet (HFD), but not a low fat diet (LFD) indicating that the parametrial fat tissue from mice fed a HFD played a role in skin carcinogenesis.

  14. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    Science.gov (United States)

    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  15. Function of SREBP1 in the Milk Fat Synthesis of Dairy Cow Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Nan Li

    2014-09-01

    Full Text Available Sterol regulatory element-binding proteins (SREBPs belong to a family of nuclear transcription factors. The question of which is the most important positive regulator in milk fat synthesis in dairy cow mammary epithelial cells (DCMECs between SREBPs or other nuclear transcription factors, such as peroxisome proliferator-activated receptor γ (PPARγ, remains a controversial one. Recent studies have found that mTORC1 (the mammalian target of rapamycin C1 regulates SREBP1 to promote fat synthesis. Thus far, however, the interaction between the SREBP1 and mTOR (the mammalian target of rapamycin pathways in the regulation of milk fat synthesis remains poorly understood. This study aimed to identify the function of SREBP1 in milk fat synthesis and to characterize the relationship between SREBP1 and mTOR in DCMECs. The effects of SREBP1 overexpression and gene silencing on milk fat synthesis and the effects of stearic acid and serum on SREBP1 expression in the upregulation of milk fat synthesis were investigated in DCMECs using immunostaining, Western blotting, real-time quantitative PCR, lipid droplet staining, and detection kits for triglyceride content. SREBP1 was found to be a positive regulator of milk fat synthesis and was shown to be regulated by stearic acid and serum. These findings indicate that SREBP1 is the key positive regulator in milk fat synthesis.

  16. Brown spider (Loxosceles intermedia) venom triggers endothelial cells death by anoikis.

    Science.gov (United States)

    Nowatzki, Jenifer; Sene, Reginaldo Vieira; Paludo, Katia Sabrina; Rizzo, Luiz Eduardo; Souza-Fonseca-Guimarães, Fernando; Veiga, Silvio Sanches; Nader, Helena Bonciani; Franco, Célia Regina C; Trindade, Edvaldo S

    2012-09-01

    Brown spider (Loxosceles sp.) venom affects the endothelium of vessels and triggers disruptive activity in the subendothelial matrix. The vascular disorders observed after venom exposure include leukocyte and platelet activation, disseminated intravascular coagulation, an increase in vessel permeability and hemorrhage into the dermis. In this study, we report additional evidence regarding the mechanism of endothelial cell cytotoxicity induced by Loxosceles intermedia venom. Exposure to venom led to endothelial cell detachment in a time-dependent manner. Loss of cell anchorage and cell-cell adhesion following venom exposure was accompanied by changes in the distribution of the α₅β₁ integrin and VE-cadherin. An ultrastructural analysis of cells treated with venom revealed morphological alterations characteristic of apoptosis. Moreover, after venom exposure, the ratio between Bax and Bcl-2 proteins was disturbed in favor of Bax. In addition, late apoptosis was only observed in cells detached by the action of venom. Accordingly, there was no increase in apoptosis when cells were exposed to L. intermedia venom in suspension, suggesting that the loss of cell anchorage provides the signal to initiate apoptosis. Thus, L. intermedia venom likely triggers endothelial cell death indirectly through an apoptotic mechanism known as anoikis.

  17. FAT10 suppression stabilizes oxidized proteins in liver cells: Effects of HCV and ethanol.

    Science.gov (United States)

    Ganesan, Murali; Hindman, Joseph; Tillman, Brittany; Jaramillo, Lee; Poluektova, Larisa I; French, Barbara A; Kharbanda, Kusum K; French, Samuel W; Osna, Natalia A

    2015-12-01

    FAT10 belongs to the ubiquitin-like modifier (ULM) family that targets proteins for degradation and is recognized by 26S proteasome. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by IFNγ and TNFα in the non-immune (liver parenchymal) cells. It is not clear how viral proteins and alcohol regulate FAT10 expression on liver cells. In this study, we aimed to investigate whether FAT10 expression on liver cells is activated by the innate immunity factor, IFNα and how HCV protein expression in hepatocytes and ethanol-induced oxidative stress affect the level of FAT10 in liver cells. For this study, we used HCV(+) transgenic mice that express structural HCV proteins and their HCV(-) littermates. Mice were fed Lieber De Carli diet (control and ethanol) as specified in the NIH protocol for chronic-acute ethanol feeding. Alcohol exposure enhanced steatosis, induced oxidative stress and decreased proteasome activity in the liversof these mice, with more robust response to ethanol in HCV(+) mice. IFNα induced transcriptional activation of FAT10 in liver cells, which was dysregulated by ethanol feeding. Accordingly, IFNα-activated expression of FAT10 in hepatocytes (measured by indirect immunofluorescent of liver tissue) was also suppressed by ethanol exposure in both HCV(+) and HCV(-) mice. This suppression was accompanied with ethanol-mediated induction of lipid peroxidation marker, 4-HNE. All aforementioned effects of ethanol were attenuated by in vivo feeding of mice with the pro-methylating agent, betaine, which exhibits strong anti-oxidant properties. Based on this study, we hypothesize that FAT10 targets oxidatively modified proteins for proteasomal degradation, and that the reduction in FAT10 levels along with decreased proteasome activity may contribute to stabilization of these altered proteins in hepatocytes. In conclusion, IFNα induced FAT10 expression, which is suppressed by ethanol feeding in both HCV

  18. Drosophila ste-20 family protein kinase, hippo, modulates fat cell proliferation.

    Directory of Open Access Journals (Sweden)

    Hongling Huang

    Full Text Available BACKGROUND: Evolutionarily conserved Hippo (Hpo pathway plays a pivotal role in the control of organ size. Although the Hpo pathway regulates proliferation of a variety of epidermal cells, its function in non-ectoderm-derived cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Through methods including fat quantification assays, starvation assays, in vivo labeling assays, we show that overexpression of Hpo in Drosophila melanogaster fat body restricts Drosophila body growth and reduces fat storage through regulation of adipocyte proliferation rather than through influencing the size of fat cells and lipid metabolism, whereas compromising Hpo activity results in weight gain and greater fat storage. Furthermore, we provide evidence that Yorkie (Yki, a transcriptional coactivator that functions in the Hpo pathway antagonizes Hpo to modulate fat storage in Drosophila. CONCLUSIONS/SIGNIFICANCE: Our findings specify a role of Hpo in controlling mesoderm-derived cell proliferation. The observed anti-obesity effects of Hpo may indicate great potential for its utilization in anti-obesity therapeutics.

  19. Protocadherin FAT1 binds Ena/VASP proteins and is necessary for actin dynamics and cell polarization

    OpenAIRE

    Moeller, Marcus J.; Soofi, Abdulsalam; Braun, Gerald S; Li, Xiaodong; Watzl, Carsten; Kriz, Wilhelm; Holzman, Lawrence B.

    2004-01-01

    Cell migration requires integration of cellular processes resulting in cell polarization and actin dynamics. Previous work using tools of Drosophila genetics suggested that protocadherin fat serves in a pathway necessary for determining cell polarity in the plane of a tissue. Here we identify mammalian FAT1 as a proximal element of a signaling pathway that determines both cellular polarity in the plane of the monolayer and directed actin-dependent cell motility. FAT1 is localized to the leadi...

  20. High fat feeding affects the number of GPR120 cells and enteroendocrine cells in the mouse stomach

    Directory of Open Access Journals (Sweden)

    Patricia eWidmayer

    2015-02-01

    Full Text Available Long-term intake of dietary fat is supposed to be associated with adaptive reactions of the organism and it is assumptive that this is particularly true for fat responsive epithelial cells in the mucosa of the gastrointestinal tract. Recent studies suggest that epithelial cells expressing the receptor for medium and long chain fatty acids, GPR120 (FFAR4, may operate as fat sensors. Changes in expression level and/or cell density are supposed to be accompanied with a consumption of high fat (HF diet. To assess whether feeding a HF diet might impact on the expression of fatty acid receptors or the number of lipid sensing cells as well as enteroendocrine cell populations, gastric tissue samples of non-obese and obese mice were compared using a real time PCR and immunohistochemical approach. In this study, we have identified GPR120 cells in the corpus region of the mouse stomach which appeared to be brush cells. Monitoring the effect of HF diet on the expression of GPR120 revealed that after 3 weeks and 6 months the level of mRNA for GPR120 in the tissue was significantly increased which coincided with and probably reflected a significant increase in the number of GPR120 positive cells in the corpus region; in contrast, within the antrum region, the number of GPR120 cells decreased. Furthermore, dietary fat intake also led to changes in the number of enteroendocrine cells producing either ghrelin or gastrin. After 3 weeks and even more pronounced after 6 months the number of ghrelin cells and gastrin cells was significantly increased. These results imply that a HF diet leads to significant changes in the cellular repertoire of the stomach mucosa. Whether these changes are a consequence of the direct exposure to high fat in the luminal content or a physiological response to the high level of fat in the body remains elusive.

  1. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival

    DEFF Research Database (Denmark)

    Kølle, Stig-Frederik Trojahn; Fischer-Nielsen, Anne; Mathiasen, Anders Bruun;

    2013-01-01

    Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival ...... of fat grafts enriched with autologous adipose-derived stem cells (ASCs) versus non-enriched fat grafts....

  2. Regulatory circuits controlling white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Kristiansen, Karsten

    2006-01-01

    Adipose tissue is a major endocrine organ that exerts a profound influence on whole-body homoeostasis. Two types of adipose tissue exist in mammals: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT stores energy and is the largest energy reserve in mammals, whereas BAT, expressing UCP......1 (uncoupling protein 1), can dissipate energy through adaptive thermogenesis. In rodents, ample evidence supports BAT as an organ counteracting obesity, whereas less is known about the presence and significance of BAT in humans. Despite the different functions of white and brown adipocytes......, knowledge of factors differentially influencing the formation of white and brown fat cells is sparse. Here we summarize recent progress in the molecular understanding of white versus brown adipocyte differentiation, including novel insights into transcriptional and signal transduction pathways. Since...

  3. Gravity separation of fat, somatic cells, and bacteria in raw and pasteurized milks.

    Science.gov (United States)

    Caplan, Z; Melilli, C; Barbano, D M

    2013-04-01

    The objective of experiment 1 was to determine if the extent of gravity separation of milk fat, bacteria, and somatic cells is influenced by the time and temperature of gravity separation or the level of contaminating bacteria present in the raw milk. The objective of experiment 2 was to determine if different temperatures of milk heat treatment affected the gravity separation of milk fat, bacteria, and somatic cells. In raw milk, fat, bacteria, and somatic cells rose to the top of columns during gravity separation. About 50 to 80% of the fat and bacteria were present in the top 8% of the milk after gravity separation of raw milk. Gravity separation for 7h at 12°C or for 22h at 4°C produced equivalent separation of fat, bacteria, and somatic cells. The completeness of gravity separation of fat was influenced by the level of bacteria in the milk before separation. Milk with a high bacterial count had less (about 50 to 55%) gravity separation of fat than milk with low bacteria count (about 80%) in 22h at 4°C. Gravity separation caused fat, bacteria, and somatic cells to rise to the top of columns for raw whole milk and high temperature, short-time pasteurized (72.6°C, 25s) whole milk. Pasteurization at ≥76.9°C for 25s prevented all 3 components from rising, possibly due to denaturation of native bovine immunoglobulins that normally associate with fat, bacteria, and somatic cells during gravity separation. Gravity separation can be used to produce reduced-fat milk with decreased bacterial and somatic cell counts, and may be a critical factor in the history of safe and unique traditional Italian hard cheeses produced from gravity-separated raw milk. A better understanding of the mechanism of this natural process could lead to the development of new nonthermal thermal technology (that does not involve heating the milk to high temperatures) to remove bacteria and spores from milk or other liquids.

  4. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole;

    1983-01-01

    Insulin resistance was studied by comparing insulin response and insulin binding in four groups of rats. Glucose metabolism in isolated fat cells from male Wistar rats weighing 340 g was less responsive to a supramaximal dose of insulin than glucose metabolism in fat cells from rats weighing 200 g...... to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism....... Induction of streptozotocin-diabetes in rats weighing 200 g resulted in a marked decrease in the insulin responsiveness of fat cells. Ventromedial hypothalamic lesions of 340 g rats had the opposite effect and restored the insulin responsiveness of fat cells. The responsiveness in the four groups was...

  5. High fat feeding affects the number of GPR120 cells and enteroendocrine cells in the mouse stomach.

    Science.gov (United States)

    Widmayer, Patricia; Goldschmid, Hannah; Henkel, Helena; Küper, Markus; Königsrainer, Alfred; Breer, Heinz

    2015-01-01

    Long-term intake of dietary fat is supposed to be associated with adaptive reactions of the organism and it is assumptive that this is particularly true for fat responsive epithelial cells in the mucosa of the gastrointestinal tract. Recent studies suggest that epithelial cells expressing the receptor for medium and long chain fatty acids, GPR120 (FFAR4), may operate as fat sensors. Changes in expression level and/or cell density are supposed to be accompanied with a consumption of high fat (HF) diet. To assess whether feeding a HF diet might impact on the expression of fatty acid receptors or the number of lipid sensing cells as well as enteroendocrine cell populations, gastric tissue samples of non-obese and obese mice were compared using a real time PCR and immunohistochemical approach. In this study, we have identified GPR120 cells in the corpus region of the mouse stomach which appeared to be brush cells. Monitoring the effect of HF diet on the expression of GPR120 revealed that after 3 weeks and 6 months the level of mRNA for GPR120 in the tissue was significantly increased which coincided with and probably reflected a significant increase in the number of GPR120 positive cells in the corpus region; in contrast, within the antrum region, the number of GPR120 cells decreased. Furthermore, dietary fat intake also led to changes in the number of enteroendocrine cells producing either ghrelin or gastrin. After 3 weeks and even more pronounced after 6 months the number of ghrelin cells and gastrin cells was significantly increased. These results imply that a HF diet leads to significant changes in the cellular repertoire of the stomach mucosa. Whether these changes are a consequence of the direct exposure to HF in the luminal content or a physiological response to the high level of fat in the body remains elusive.

  6. Application of a clinical grade CD34-mediated method for the enrichment of microvascular endothelial cells from fat tissue.

    NARCIS (Netherlands)

    Arts, C.H.; Groot, P. de; Heijnen-Snyder, G.J.; Blankensteijn, J.D.; Eikelboom, B.C.; Slaper-Cortenbach, I.C.M.

    2004-01-01

    BACKGROUND: Microvascular endothelial cells (MVEC) derived from s.c. fat are seeded on vascular grafts to prevent early occlusion. We have demonstrated the presence of contaminating cells contributing to MVEC seeding-related intimal hyperplasia in MVEC isolates from fat tissue. We found that cell is

  7. Application of a clinical grade CD34-mediated method for the enrichment of microvascular endothelial cells from fat tissue

    NARCIS (Netherlands)

    Arts, CHP; de Groot, PG; Heijnen-Snyder, GJ; Blankensgteijn, JD; Eikelboom, BC; Slaper-Cortenbach, ICM

    2004-01-01

    Background Microvascular endothelial cells (MVEC) derived from s.c. fat are seeded on vascular grafts to prevent early occlusion. We have demonstrated the presence of contaminating cells contributing to MVEC seeding-related intimal hyperplasia in MVEC isolates from fat tissue. We found that cell iso

  8. Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Cherry, E-mail: cherrykim0505@gmail.com; Choi, Hyuck Jae, E-mail: choihj@amc.seoul.kr; Cho, Kyoung-Sik, E-mail: kscho@amc.seoul.kr

    2014-06-15

    Objective: Although renal sinus fat invasion has prognostic significance in patients with renal cell carcinomas (RCCs), there are no previous studies about the value of multidetector computed tomography (MDCT) about this issue in the current literature. Materials and methods: A total of 863 consecutive patients (renal sinus fat invasion in 110 patients (12.7%)) from single institutions with surgically-confirmed renal cell carcinoma who underwent MDCT between 2010 and 2012 were included in this study. The area under the curves (AUCs) of the receiver operating characteristic (ROC) analysis was used to compare diagnostic performance. Reference standard was pathologic examination. Weighted κ statistics were used to measure the level of interobserver agreement. Multivariate logistic regression model was used to find the predictors for renal sinus fat invasion. Image analysis was first performed with axial-only CT images. A second analysis was then performed with both axial and coronal CT images. A qualitative analysis was then conducted by two reviewers who reached consensus regarding tumor size, decreased perfusion, tumor margin, vessel displacement, and lymph node metastasis. The reference standard was pathologic evaluation. Results: The AUCs of the ROC analysis were 0.881 and 0.922 for axial-only images and 0.889 and 0.902 for combined images in both readers. The AUC of tumor size was 0.884, a similar value to that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or nodular type of fat infiltration, and an irregular tumor margin were independent predicting factors for perinephric fat invasion. Conclusion: MDCT shows relatively high diagnostic performance in detecting perinephric fat invasion of RCC but suffers from a relatively low PPV related to low prevalence of renal sinus fat invasion. Applying tumor size alone we could get similar diagnostic performance to those of radiologists. Tumor size, fat infiltration with a nodular appearance, and

  9. Cytotoxic activity of some marine brown algae against cancer cell lines.

    Science.gov (United States)

    Khanavi, Mahnaz; Nabavi, Maryam; Sadati, Nargess; Shams Ardekani, Mohammadreza; Sohrabipour, Jelve; Nabavi, Seyed Mohammad B; Ghaeli, Padideh; Ostad, Seyed Nasser

    2010-01-01

    The aim of this study was to investigate the in vitro cytotoxic activity of total extract of MeOH (70%) and partition fractions of hexan, chloroform (CHCL3), ethylacetate (EtOAc) and MeOH-H2O of brown algae species (Sargassum swartzii, Cystoseira myrica, Colpomenia sinuosa) found in the Persian Gulf against in different cell lines including HT-29, Caco-2, T47D, MDA-MB468 and NIH 3T3 cell lines by MTT and AnnexinV-PI assay. The hexan fraction of S. swartzii and C. myrica showed selective cytotoxicity against proliferation of Caco-2 cells (IC50 hexan fraction of C. myrica on T47D parent cells was lower than it was on T47D-TR cells (IC50 99.9 ± 8.11 vs. 143.15 ± 7.80). This finding suggests a role for the MDR-1 in the development of possible future tolerance to the extract. PMID:21157630

  10. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone

    Data.gov (United States)

    U.S. Environmental Protection Agency — pulmonary parameters, BALF biomarkers, body composition, motor activity data collected from rats exposed to ozone after high fructose or high fat diets. This...

  11. Signaling Pathway Puts the Break on Fat Cell Formation

    Directory of Open Access Journals (Sweden)

    Ormond A. MacDougald

    2001-01-01

    Full Text Available Obesity is approaching epidemic proportions in the western industrialized world, and is also becoming a major problem among young people in eastern and developing countries [1,2,3]. Unfortunately, excess fat or adipose tissue is associated with a wide array of health problems, including increased incidence of type II diabetes, cardiovascular disease, hypertension, sleep apnea, and skeletomuscular problems [4,5,6]. Obesity is the second leading cause of death from “unnecessary” causes in the U.S. (after smoking, and costs individuals and society billions of dollars worldwide to treat. Despite common wisdom that “one just needs to eat less and exercise more” and a multi-billion-dollar diet industry, epidemiological data indicate that the incidence of obesity will continue to rise. This alarming trend is, in part, due to the unprecedented availability of energy-dense foods and an increasingly sedentary lifestyle. These environmental factors may be complicated in some individuals by an unfavorable genetic predisposition. Pharmaceutical companies lead active research programs to identify drugs that target weight control centers in the body and which may help individuals control their weight; however, no satisfactory magic bullet to fight obesity has yet come through the pipeline [7,8].

  12. Seasonal and Milking-to-Milking Variations in Cow Milk Fat, Protein and Somatic Cell Counts

    OpenAIRE

    Elena Raluca PAVEL; Constantin GAVAN

    2011-01-01

    The first objective of this study was to examine milking-to-milking variations in milk fat, protein and SCC (somatic cell count). The second objective of this study was to examine variations of milk components (fat, protein and SCC) over a period of six months (April-September 2010) at Agricultural Research Development Station Simnic. A total of 128 milk samples (64 morning milking and 64 evening milking ones) from milk bulk tank commingled from 90�4 Holstein cows, were collected and analyzed...

  13. Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1

    Directory of Open Access Journals (Sweden)

    Hannah Seok

    2012-08-01

    Full Text Available BackgroundThe aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.MethodsIn this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF rats were fed a normal chow diet or a high-fat diet (HFD and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.ResultsIn rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1 expression in islets and decreased cholesterol levels.ConclusionThese findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression.

  14. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Jørgensen, Claus; Petersen, Rasmus K;

    2004-01-01

    fibroblasts (MEFs) and white preadipocytes by expression of simian virus 40 large T antigen results in the expression of the brown fat-specific uncoupling protein 1 (UCP-1) in the adipose state. Retinoblastoma gene-deficient (Rb-/-) MEFs and stem cells, but not the corresponding wild-type cells, differentiate...... into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. pRB-deficient MEFs exhibit an increased expression of the Forkhead transcription factor Foxc2 and its target gene cAMP-dependent protein kinase regulatory subunit RIalpha, resulting in increased c...... at a developmental stage where both cell types begin to accumulate lipid and brown adipocytes express UCP-1. Furthermore, pRB rapidly undergoes phosphorylation upon cold-induced neodifferentiation and up-regulation of UCP-1 expression in brown adipose tissue. Finally, down-regulation of pRB expression accompanies...

  15. Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Chien-Min Hung

    2014-07-01

    Full Text Available The in vivo functions of mechanistic target of rapamycin complex 2 (mTORC2 and the signaling mechanisms that control brown adipose tissue (BAT fuel utilization and activity are not well understood. Here, by conditionally deleting Rictor in the Myf5 lineage, we provide in vivo evidence that mTORC2 is dispensable for skeletal muscle development and regeneration but essential for BAT growth. Furthermore, deleting Rictor in Myf5 precursors shifts BAT metabolism to a more oxidative and less lipogenic state and protects mice from obesity and metabolic disease at thermoneutrality. We additionally find that Rictor is required for brown adipocyte differentiation in vitro and that the mechanism specifically requires AKT1 hydrophobic motif phosphorylation but is independent of pan-AKT signaling and is rescued with BMP7. Our findings provide insights into the signaling circuitry that regulates brown adipocytes and could have important implications for developing therapies aimed at increasing energy expenditure as a means to combat human obesity.

  16. The Ontogeny of Brown Adipose Tissue.

    Science.gov (United States)

    Symonds, Michael E; Pope, Mark; Budge, Helen

    2015-01-01

    There are three different types of adipose tissue (AT)-brown, white, and beige-that differ with stage of development, species, and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein 1 (UCP1) located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whereas beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence, and adulthood. We focus on the interrelationships between adipocyte classification, anatomical location, and impact of diet in early life together with the extent to which fat development differs between the major species examined. Ultimately, novel dietary interventions designed to reactivate BAT could be possible.

  17. Biomimetic fat cell (BFC) preparation and for lindane removal from aqueous solution.

    Science.gov (United States)

    Liyan, Song; Youcai, Zhao; Guojian, Wang; Bing, Li; Dongjie, Niu; Xiaoli, Chai

    2007-07-19

    Fat tissue of organism can accumulate hydrophobic chemicals efficiently and the accumulation level has a positive correlation with fat quantity. In this work, based on this characteristic, an innovative agent, that is, biomimetic fat cell (BFC) has been synthesized with interfacial polymerization. BFC has a hydrophobic nucleolus-triolein and hydrophilic membrane-polyamide, through which water, carrying hydrophobic organic contaminants (HOCs), can pass. This process is followed by the accumulation of HOCs. BFC has 97.39% lindane removal ability. This is close to 98.12% lindane removal by powder active carbon (PAC) in aqueous solution and 7 mg/L initial concentration of lindane. BFC can be regenerated easily by organic solvent dialysis in comparison with high temperature or pressure used for PAC regeneration. Lindane removal by BFC may occur through two mechanisms: bioaccumulation by BFC nucleolus-triolein; and adsorption by BFC membrane. Bioaccumulation is the prevailing mechanism.

  18. Transient brown adipocyte-like cells derive from peripheral nerve progenitors in response to bone morphogenetic protein 2.

    Science.gov (United States)

    Salisbury, Elizabeth A; Lazard, Zawaunyka W; Ubogu, Eroboghene E; Davis, Alan R; Olmsted-Davis, Elizabeth A

    2012-12-01

    Perineurial-associated brown adipocyte-like cells were rapidly generated during bone morphogenetic protein 2 (BMP2)-induced sciatic nerve remodeling in the mouse. Two days after intramuscular injection of transduced mouse fibroblast cells expressing BMP2 into wild-type mice, there was replication of beta-3 adrenergic receptor(+) (ADRB3(+)) cells within the sciatic nerve perineurium. Fluorescence-activated cell sorting and analysis of cells isolated from these nerves confirmed ADRB3(+) cell expansion and their expression of the neural migration marker HNK1. Similar analysis performed 4 days after BMP2 delivery revealed a significant decrease in ADRB3(+) cells from isolated sciatic nerves, with their concurrent appearance within the adjacent soft tissue, suggesting migration away from the nerve. These soft tissue-derived cells also expressed the brown adipose marker uncoupling protein 1 (UCP1). Quantification of ADRB3-specific RNA in total hind limb tissue revealed a 3-fold increase 2 days after delivery of BMP2, followed by a 70-fold increase in UCP1-specific RNA after 3 days. Expression levels then rapidly returned to baseline by 4 days. Interestingly, these ADRB3(+) UCP1(+) cells also expressed the neural guidance factor reelin. Reelin(+) cells demonstrated distinct patterns within the injected muscle, concentrated toward the area of BMP2 release. Blocking mast cell degranulation-induced nerve remodeling resulted in the complete abrogation of UCP1-specific RNA and protein expression within the hind limbs following BMP2 injection. The data collectively suggest that local BMP2 administration initiates a cascade of events leading to the expansion, migration, and differentiation of progenitors from the peripheral nerve perineurium to brown adipose-like cells in the mouse, a necessary prerequisite for associated nerve remodeling. PMID:23283549

  19. Dchs1–Fat4 regulation of polarized cell behaviours during skeletal morphogenesis

    OpenAIRE

    Mao, Yaopan; Kuta, Anna; Crespo-Enriquez, Ivan; Whiting, Danielle; Martin, Tina; Mulvaney, Joanna; Irvine, Kenneth D.; Francis-West, Philippa

    2016-01-01

    Skeletal shape varies widely across species as adaptation to specialized modes of feeding and locomotion, but how skeletal shape is established is unknown. An example of extreme diversity in the shape of a skeletal structure can be seen in the sternum, which varies considerably across species. Here we show that the Dchs1-Fat4 planar cell polarity pathway controls cell orientation in the early skeletal condensation to define the shape and relative dimensions of the mouse sternum. These changes...

  20. Lipoprotein lipase links dietary fat to solid tumor cell proliferation

    OpenAIRE

    Kuemmerle, Nancy B.; Rysman, Evelien; Lombardo, Portia S.; Flanagan, Alison J.; Lipe, Brea C.; Wells, Wendy A.; Pettus, Jason R.; Froehlich, Heather M.; Memoli, Vincent A.; Morganelli, Peter M.; Swinnen, Johannes V.; Timmerman, Luika A.; Chaychi, Leila; Fricano, Catherine J.; Eisenberg, Burton L.

    2011-01-01

    Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain pre-formed, diet-derived fatty acids by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, th...

  1. Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring

    Directory of Open Access Journals (Sweden)

    Hadiza Altine Adamu

    2016-02-01

    Full Text Available Background: Evidence suggests perinatal environments influence the risk of developing insulin resistance. Objective: The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR and GBR-derived gamma (γ aminobutyric acid (GABA extract on epigenetically mediated high fat diet–induced insulin resistance. Design: Pregnant Sprague Dawley rats were fed high-fat diet (HFD, HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4 were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. Results: Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. Conclusions: These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis.

  2. Comparison of brown and white adipose tissue fat fractions in ob, seipin, and Fsp27 gene knockout mice by chemical shift-selective imaging and (1)H-MR spectroscopy.

    Science.gov (United States)

    Peng, Xin-Gui; Ju, Shenghong; Fang, Fang; Wang, Yu; Fang, Ke; Cui, Xin; Liu, George; Li, Peng; Mao, Hui; Teng, Gao-Jun

    2013-01-15

    Brown adipose tissue (BAT) plays a key role in thermogenesis to protect the body from cold and obesity. White adipose tissue (WAT) stores excess energy in the form of triglycerides. To better understand the genetic effect on regulation of WAT and BAT, we investigated the fat fraction (FF) in two types of adipose tissues in ob/ob, human BSCL2/seipin gene knockout (SKO), Fsp27 gene knockout (Fsp27(-/-)), and wild-type (WT) mice in vivo using chemical shift selective imaging and (1)H-MR spectroscopy. We reported that the visceral fat volume in WAT was significantly larger in ob/ob mice, but visceral fat volumes were lower in SKO and Fsp27(-/-) mice compared with WT mice. BAT FF was significantly higher in ob/ob mice than the WT group and similar to that of WAT. In contrast, WAT FFs in SKO and Fsp27(-/-) mice were lower and similar to that of BAT. The adipocyte size of WAT in ob/ob mice and the BAT adipocyte size in ob/ob, SKO, and Fsp27 mice were significantly larger compared with WT mice. However, the WAT adipocyte size was significantly smaller in SKO mice than in WT mice. Positive correlations were observed between the adipocyte size and FFs of WAT and BAT. These results suggested that smaller adipocyte size correlates with lower FFs of WAT and BAT. In addition, the differences in FFs in WAT and BAT measured by MR methods in different mouse models were related to the different regulation effects of ob, seipin, or Fsp27 gene on developing WAT and BAT.

  3. Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity

    Science.gov (United States)

    Hafner, Anne-Laure; Contet, Julian; Ravaud, Christophe; Yao, Xi; Villageois, Phi; Suknuntha, Kran; Annab, Karima; Peraldi, Pascal; Binetruy, Bernard; Slukvin, Igor I.; Ladoux, Annie; Dani, Christian

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) show great promise for obesity treatment as they represent an unlimited source of brown/brite adipose progenitors (BAPs). However, hiPSC-BAPs display a low adipogenic capacity compared to adult-BAPs when maintained in a traditional adipogenic cocktail. The reasons of this feature are unknown and hamper their use both in cell-based therapy and basic research. Here we show that treatment with TGFβ pathway inhibitor SB431542 together with ascorbic acid and EGF were required to promote hiPSCs-BAP differentiation at a level similar to adult-BAP differentiation. hiPSC-BAPs expressed the molecular identity of adult-UCP1 expressing cells (PAX3, CIDEA, DIO2) with both brown (ZIC1) and brite (CD137) adipocyte markers. Altogether, these data highlighted the critical role of TGFβ pathway in switching off hiPSC-brown adipogenesis and revealed novel factors to unlock their differentiation. As hiPSC-BAPs display similarities with adult-BAPs, it opens new opportunities to develop alternative strategies to counteract obesity. PMID:27577850

  4. Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity.

    Science.gov (United States)

    Hafner, Anne-Laure; Contet, Julian; Ravaud, Christophe; Yao, Xi; Villageois, Phi; Suknuntha, Kran; Annab, Karima; Peraldi, Pascal; Binetruy, Bernard; Slukvin, Igor I; Ladoux, Annie; Dani, Christian

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) show great promise for obesity treatment as they represent an unlimited source of brown/brite adipose progenitors (BAPs). However, hiPSC-BAPs display a low adipogenic capacity compared to adult-BAPs when maintained in a traditional adipogenic cocktail. The reasons of this feature are unknown and hamper their use both in cell-based therapy and basic research. Here we show that treatment with TGFβ pathway inhibitor SB431542 together with ascorbic acid and EGF were required to promote hiPSCs-BAP differentiation at a level similar to adult-BAP differentiation. hiPSC-BAPs expressed the molecular identity of adult-UCP1 expressing cells (PAX3, CIDEA, DIO2) with both brown (ZIC1) and brite (CD137) adipocyte markers. Altogether, these data highlighted the critical role of TGFβ pathway in switching off hiPSC-brown adipogenesis and revealed novel factors to unlock their differentiation. As hiPSC-BAPs display similarities with adult-BAPs, it opens new opportunities to develop alternative strategies to counteract obesity. PMID:27577850

  5. Comparative Analysis of the miRNome of Bovine Milk Fat, Whey and Cells

    Science.gov (United States)

    Li, Ran; Dudemaine, Pier-Luc; Zhao, Xin; Lei, Chuzhao; Ibeagha-Awemu, Eveline Mengwi

    2016-01-01

    Abundant miRNAs have been identified in milk and mammary gland tissues of different species. Typically, RNA in milk can be extracted from different fractions including fat, whey and cells and the mRNA transcriptome of milk could serve as an indicator of the transcriptome of mammary gland tissue. However, it has not been adequately validated if the miRNA transcriptome of any milk fraction could be representative of that of mammary gland tissue. The objectives of this study were to (1) characterize the miRNA expression spectra from three milk fractions- fat, whey and cells; (2) compare miRNome profiles of milk fractions (fat, whey and cells) with mammary gland tissue miRNome, and (3) determine which milk fraction miRNome profile could be a better representative of the miRNome profile of mammary gland tissue. Milk from four healthy Canadian Holstein cows in mid lactation was collected and fractionated. Total RNA extracted from each fraction was used for library preparation followed by small RNA sequencing. In addition, miRNA transcripts of mammary gland tissues from twelve Holstein cows in our previous study were used to compare our data. We identified 210, 200 and 249 known miRNAs from milk fat, whey and cells, respectively, with 188 universally expressed in the three fractions. In addition, 33, 31 and 36 novel miRNAs from milk fat, whey and cells were identified, with 28 common in the three fractions. Among 20 most highly expressed miRNAs in each fraction, 14 were expressed in common and 11 were further shared with mammary gland tissue. The three milk fractions demonstrated a clear separation from each other using a hierarchical cluster analysis with milk fat and whey being most closely related. The miRNome correlation between milk fat and mammary gland tissue (rmean = 0.866) was significantly higher than the other two pairs (p milk cell/mammary gland tissue (rmean = 0.75), suggesting that milk fat could be an alternative non-invasive source of RNA in assessing mi

  6. Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice

    Science.gov (United States)

    Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

  7. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice.

    Science.gov (United States)

    Rosell, Meritxell; Kaforou, Myrsini; Frontini, Andrea; Okolo, Anthony; Chan, Yi-Wah; Nikolopoulou, Evanthia; Millership, Steven; Fenech, Matthew E; MacIntyre, David; Turner, Jeremy O; Moore, Jonathan D; Blackburn, Edith; Gullick, William J; Cinti, Saverio; Montana, Giovanni; Parker, Malcolm G; Christian, Mark

    2014-04-15

    Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a "brite" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with "browning," as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.

  8. Fat Necrosis and Oil Cysts

    Science.gov (United States)

    ... Granular cell tumors Fat necrosis and oil cysts Mastitis Duct ectasia Other non-cancerous breast conditions Summary ... References Previous Topic Granular cell tumors Next Topic Mastitis Fat necrosis and oil cysts Fat necrosis happens ...

  9. Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex

    Directory of Open Access Journals (Sweden)

    Ganesh Kolumam

    2015-07-01

    Full Text Available Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin.

  10. Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex

    Science.gov (United States)

    Kolumam, Ganesh; Chen, Mark Z.; Tong, Raymond; Zavala-Solorio, Jose; Kates, Lance; van Bruggen, Nicholas; Ross, Jed; Wyatt, Shelby K.; Gandham, Vineela D.; Carano, Richard A.D.; Dunshee, Diana Ronai; Wu, Ai-Luen; Haley, Benjamin; Anderson, Keith; Warming, Søren; Rairdan, Xin Y.; Lewin-Koh, Nicholas; Zhang, Yingnan; Gutierrez, Johnny; Baruch, Amos; Gelzleichter, Thomas R.; Stevens, Dale; Rajan, Sharmila; Bainbridge, Travis W.; Vernes, Jean-Michel; Meng, Y. Gloria; Ziai, James; Soriano, Robert H.; Brauer, Matthew J.; Chen, Yongmei; Stawicki, Scott; Kim, Hok Seon; Comps-Agrar, Laëtitia; Luis, Elizabeth; Spiess, Christoph; Wu, Yan; Ernst, James A.; McGuinness, Owen P.; Peterson, Andrew S.; Sonoda, Junichiro

    2015-01-01

    Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin. PMID:26288846

  11. STIM1 regulates calcium signaling in taste bud cells and preference for fat in mice

    Science.gov (United States)

    Dramane, Gado; Abdoul-Azize, Souleymane; Hichami, Aziz; VÖgtle, Timo; Akpona, Simon; Chouabe, Christophe; Sadou, Hassimi; Nieswandt, Bernhard; Besnard, Philippe; Khan, Naim Akhtar

    2012-01-01

    Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. The lipid-binding glycoprotein CD36, which is expressed by circumvallate papillae (CVP) of the mouse tongue, has been implicated in oro-gustatory perception of dietary lipids. Here, we demonstrate that stromal interaction molecule 1 (STIM1), a sensor of Ca2+ depletion in the endoplasmic reticulum, mediates fatty acid–induced Ca2+ signaling in the mouse tongue and fat preference. We showed that linoleic acid (LA) induced the production of arachidonic acid (AA) and lysophosphatidylcholine (Lyso-PC) by activating multiple phospholipase A2 isoforms via CD36. This activation triggered Ca2+ influx in CD36-positive taste bud cells (TBCs) purified from mouse CVP. LA also induced the production of Ca2+ influx factor (CIF). STIM1 was found to regulate LA-induced CIF production and the opening of multiple store-operated Ca2+ (SOC) channels. Furthermore, CD36-positive TBCs from Stim1–/– mice failed to release serotonin, and Stim1–/– mice lost the spontaneous preference for fat that was observed in wild-type animals. Our results suggest that fatty acid–induced Ca2+ signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat. PMID:22546859

  12. Glucose and lipid metabolism in insulin resistance : an experimental study in fat cells

    OpenAIRE

    Burén, Jonas

    2003-01-01

    Type 2 diabetes is usually caused by a combination of pancreatic β-cell failure and insulin resistance in target tissues like liver, muscle and fat. Insulin resistance is characterised by an impaired effect of insulin to reduce hepatic glucose production and to promote glucose uptake in peripheral tissues. The focus of this study was to further elucidate cellular mechanisms for insulin resistance that may be of relevance for type 2 diabetes in humans. We used rat and human adipocytes as an es...

  13. Methanolic Extracts from Brown Seaweeds Dictyota cilliolata and Dictyota menstrualis Induce Apoptosis in Human Cervical Adenocarcinoma HeLa Cells

    Directory of Open Access Journals (Sweden)

    Dayanne Lopes Gomes

    2015-04-01

    Full Text Available Carcinoma of the uterine cervix is the second most common female tumor worldwide, surpassed only by breast cancer. Natural products from seaweeds evidencing apoptotic activity have attracted a great deal of attention as new leads for alternative and complementary preventive or therapeutic anticancer agents. Here, methanol extracts from 13 species of tropical seaweeds (Rhodophytas, Phaeophyta and Chlorophyta collected from the Northeast of Brazil were assessed as apoptosis-inducing agents on human cervical adenocarcinoma (HeLa. All extracts showed different levels of cytotoxicity against HeLa cells; the most potent were obtained from the brown alga Dictyota cilliolata (MEDC and Dictyota menstrualis (MEDM. In addition, MEDC and MEDM also inhibits SiHa (cervix carcinoma cell proliferation. Studies with these two extracts using flow cytometry and fluorescence microscopy showed that HeLa cells exposed to MEDM and MEDC exhibit morphological and biochemical changes that characterize apoptosis as shown by loss of cell viability, chromatin condensation, phosphatidylserine externalization, and sub-G1 cell cycle phase accumulation, also MEDC induces cell cycle arrest in cell cycle phase S. Moreover, the activation of caspases 3 and 9 by these extracts suggests a mitochondria-dependent apoptosis route. However, other routes cannot be ruled out. Together, these results point out the methanol extracts of the brown algae D. mentrualis and D. cilliolata as potential sources of molecules with antitumor activity.

  14. Fat3 and Ena/VASP proteins influence the emergence of asymmetric cell morphology in the developing retina.

    Science.gov (United States)

    Krol, Alexandra; Henle, Steven J; Goodrich, Lisa V

    2016-06-15

    Neurons exhibit asymmetric morphologies throughout development - from migration to the elaboration of axons and dendrites - that are correctly oriented for the flow of information. For instance, retinal amacrine cells migrate towards the inner plexiform layer (IPL) and then retract their trailing processes, thereby acquiring a unipolar morphology with a single dendritic arbor restricted to the IPL. Here, we provide evidence that the Fat-like cadherin Fat3 acts during multiple stages of amacrine cell development in mice to orient overall changes in cell shape towards the IPL. Using a time-lapse imaging assay, we found that developing amacrine cells are less directed towards the IPL in the absence of Fat3, during both migration and retraction. Consistent with its predicted role as a cell-surface receptor, Fat3 functions cell-autonomously and is able to influence the cytoskeleton directly through its intracellular domain, which can bind and localize Ena/VASP family actin regulators. Indeed, a change in Ena/VASP protein distribution is sufficient to recapitulate the Fat3 mutant amacrine cell phenotype. Thus, Fat-like proteins might control the polarized development of tissues by sculpting the cytoskeleton of individual cells.

  15. Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro.

    Science.gov (United States)

    Caminhotto, R de O; Sertié, R A L; Andreotti, S; Campaãa, A B; Lima, F B

    2016-07-28

    Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (-19% of maximal response and -60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (-19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients. PMID:27487419

  16. Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice

    Directory of Open Access Journals (Sweden)

    Altintas Mehmet M

    2012-02-01

    Full Text Available Abstract Background Mast cells are implicated in the pathogenesis of obesity and insulin resistance. Here, we explored the effects of leptin deficiency-induced obesity on the density of mast cells in metabolic (abdominal fat depots, skeletal muscle, and liver and lymphatic (abdominal lymph nodes, spleen, and thymus organs. Fourteen-week-old male leptin-deficient ob/ob mice and their controls fed a standard chow were studied. Tissue sections were stained with toluidine blue to determine the density of mast cells. CD117/c-kit protein expression analysis was also carried out. Furthermore, mast cells containing immunoreactive tumor necrosis factor-α (TNF-α, a proinflammatory cytokine involved in obesity-linked insulin resistance, were identified by immunostaining. Results ob/ob mice demonstrated adiposity and insulin resistance. In abdominal fat depots, mast cells were distributed differentially. While most prevalent in subcutaneous fat in controls, mast cells were most abundant in epididymal fat in ob/ob mice. Leptin deficiency-induced obesity was accompanied by a 20-fold increase in the density of mast cells in epididymal fat, but a 13-fold decrease in subcutaneous fat. This finding was confirmed by CD117/c-kit protein expression analysis. Furthermore, we found that a subset of mast cells in epididymal and subcutaneous fat were immunoreactive for TNF-α. The proportion of mast cells immunoreactive for TNF-α was higher in epididymal than in subcutaneous fat in both ob/ob and control mice. Mast cells were also distributed differentially in retroperitoneal, mesenteric, and inguinal lymph nodes. In both ob/ob mice and lean controls, mast cells were more prevalent in retroperitoneal than in mesenteric and inguinal lymph nodes. Leptin deficiency-induced obesity was accompanied by increased mast cell density in all lymph node stations examined. No significant difference in the density of mast cells in skeletal muscle, liver, spleen, and thymus was

  17. Oxygen deprivation and the cellular response to hypoxia in adipocytes - perspectives on white and brown adipose tissues in obesity.

    Science.gov (United States)

    Trayhurn, Paul; Alomar, Suliman Yousef

    2015-01-01

    Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4, and VEGF), an increase in glucose utilization and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has reported low pO2 in brown fat of obese mice, this involving mitochondrial loss and dysfunction. We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells - particularly changes in adipokine production, increased glucose uptake and lactate release, and insulin resistance. This would be expected to compromise thermogenic activity and the role of brown fat in glucose homeostasis and triglyceride clearance, underpinning the development of the metabolic syndrome. Hypoxia-induced augmentation of lactate production may also stimulate the "browning" of white fat depots through recruitment of UCP1 and the development of brite adipocytes.

  18. 小鼠棕色脂肪原代培养模型的建立%Establishment of culture model for primary mouse brown adipocyte precursor cells

    Institute of Scientific and Technical Information of China (English)

    刘娟; 王龙; 胡淼; 丁国宪

    2011-01-01

    目的:探索小鼠棕色脂肪细胞原代培养的方法.方法:取C57BL/6J小鼠棕色脂肪组织,采用胶原酶消化过滤法获得梭形细胞,对培养出来的细胞进行形态学观察,诱导分化后用油红O染色法染色定性,荧光定量PCR检测棕色脂肪标志基因表达情况.结果:培养出的梭形细胞成分均一,增殖旺盛,诱导分化后分化率高,经油红O染色证实为脂肪细胞,荧光定量PCR检测棕色脂肪标志基因UCP-1表达量明显升高.结论:从C57BL/6J小鼠棕色脂肪组织中可以分离出具有很强增殖、分化能力的前棕色脂肪细胞,这种棕色脂肪细胞原代培养模型的建立为在体外进一步研究棕色脂肪的功能提供了良好的基础.%Objective: To establish a culture method for primary mouse brown adipocyte precursor cells. Methods:Fibroblast-like cells were collected from C57BL/6J mice brown adipose tissue. The morphological changes of the cultured cells were observed, the in-tracytoplasmic lipid of the culture cells was determined using oil red 0 staining,and the expression of the brown adipocyte specific gene was determined by real time PCR. Results: The cultured fibroblast-like cells showed highly homogeneous appearance with ac tive proliferation and differentiate into mature adipocytes. Oil red 0 staining, morphological observation, and expression of brown adipocyte specific gene UCP-1 verified these cells as brown adipocyte. Conclusion: Brown adipocyte precursor cells are present in C57BL/6J mice brown adipose tissue and possess the potential to proliferate and differentiate into mature brown adipocyte. The estab lishment of primary culture of mouse brown adipocyte precursor cells is important for furth studies of the function of brown adipocyte in vitro.

  19. Genetic background impacts soluble and cell wall-bound aromatics in brown midrib mutants of sorghum

    Science.gov (United States)

    To evaluate the effects that genetic background has on two sorghum brown midrib (bmr) mutants, plant phenolics, lignin biosynthetic enzymes and stem anatomy were evaluated in wild-type (WT), bmr-6, bmr-12 and double-mutants (bmr-6 and bmr-12) in near isogenic , RTx430 and Wheatland backgrounds. The...

  20. Thermogenic activity of UCP1 in human white fat-derived beige adipocytes.

    Science.gov (United States)

    Bartesaghi, Stefano; Hallen, Stefan; Huang, Li; Svensson, Per-Arne; Momo, Remi A; Wallin, Simonetta; Carlsson, Eva K; Forslöw, Anna; Seale, Patrick; Peng, Xiao-Rong

    2015-01-01

    Heat-producing beige/brite (brown-in-white) adipocytes in white adipose tissue have the potential to suppress metabolic disease in mice and hold great promise for the treatment of obesity and type 2 diabetes in humans. Here, we demonstrate that human adipose-derived stromal/progenitor cells (hASCs) from subcutaneous white adipose tissue can be efficiently converted into beige adipocytes. Upon pharmacological activation of peroxisome proliferator-activated receptor-γ, hASC-derived adipocytes activated beige fat-selective genes and a brown/beige fat-selective electron transport chain gene program. Importantly, hASC-derived beige fat cells displayed the bioenergetic characteristics of genuine brown fat cells, including a capacity for increased respiratory uncoupling in response to β-adrenergic agonists. Furthermore, knock-down experiments reveal that the thermogenic capacity of human beige fat cells was entirely dependent on the presence of Uncoupling protein 1. In summary, this study reveals that hASCs can be readily differentiated into beige adipocytes that, upon activation, undergo uncoupling protein 1-dependent thermogenesis.

  1. 棕色脂肪剔除对高脂饲料诱导的肥胖小鼠体脂肪及血脂的影响%Effect of brown adipose tissue depletion on body fat and blood lipid induced by high fat diet in obesity mice

    Institute of Scientific and Technical Information of China (English)

    张永; 刘英华; 张新胜; 于晓明; 徐庆; 王觐; 宫雪; 杨雪艳; 薛长勇

    2012-01-01

    目的 观察棕色脂肪剔除对高脂饲料诱导的肥胖小鼠体脂肪及血脂的影响.方法 选择4-5周龄C57BL/6J雄性小鼠22只,随机分为肩胛下棕色脂肪剔除组和手术对照两组,每组11只,术后均喂饲高脂饲料16周.观察两组小鼠体质量、体脂肪、Lee氏指数、饲料消耗量、食物功效比及血脂的差异.结果 研究结束时,棕色脂肪剔除组小鼠的体质量、体脂肪量、Lee氏指数及血甘油三酯浓度均显著高于对照组(P<0.05),棕色脂肪剔除组食物功效比显著低于手术对照组(P<0.05),两组小鼠饲料消耗量及能量摄入量均无统计学差异(P>0.05).结论 在棕色脂肪剔除情况下,高脂饲料喂养的小鼠体内脂肪蓄积增加、肥胖度增加、血甘油三酯浓度增加,提示小鼠棕色脂肪对防止肥胖的发生具有一定作用.%Objective To observe the effect of brown adipose tissue(BAT) depletion on body fat and blood lipid induced by high fat diet in obesity mice. Methods Twenty-two male C57BL/6J mice at the age of 4-5 weeks were randomly divided into BAT depletion group and control group, 11 in each group. Their body fat mass, body fat, Lee's index, diet consumption, food efficiency ratio and blood lipid were observed after they were fed with high fat diet for 16 weeks. Results At the end of study, the body fat mass, body fat, Lee's index and triglyceride level were significantly higher while the food efficiency ratio was significantly lower in BAT depletion group than in control group(P0.05). Conclusion Fat is accumulated, obesity becomes severe and triglyceride level is higher in mice fed with high fat diet when their BAT is depleted, suggesting that BAT plays a certain role in preventing obesity.

  2. Cell signaling mechanisms of oro-gustatory detection of dietary fat: advances and challenges.

    Science.gov (United States)

    Gilbertson, Timothy A; Khan, Naim A

    2014-01-01

    CD36 and two G-protein coupled receptors (GPCR), i.e., GPR120 and GPR40, have been implicated in the gustatory perception of dietary fats in rodents. These glycoproteins are coupled to increases in free intracellular Ca²⁺ concentrations, [Ca²⁺](i), during their activation by dietary long-chain fatty acids (LCFA). The transient receptor potential type M5 (TRPM5) channel, activated by [Ca²⁺](i), participates in downstream signaling in taste bud cells (TBC). The mice, knocked-out for expression of CD36, GPR120, GPR40 or TRPM5 have a reduced spontaneous preference for fat. The delayed rectifying K⁺ (DRK) channels believed to lie downstream of these receptors are also important players in fat taste transduction. The trigeminal neurons by triggering increases in [Ca²⁺](i) may influence the taste signal to afferent nerve fibers. Why are there so many taste receptor candidates for one taste modality? We discuss the recent advances on the role of CD36, GPR120, GPR40, TRPM5 and DRK channels, in signal transduction in TBC. We shed light on their cross-talk and delineate their roles in obesity as a better understanding of the molecular mechanisms behind their regulation could eventually lead to new strategies to fight against this condition.

  3. Between brown and white: novel aspects of adipocyte differentiation.

    Science.gov (United States)

    Cinti, Saverio

    2011-03-01

    In all mammals including humans, most white and brown adipocytes are found together in visceral and subcutaneous depots (adipose organ) despite the well known difference in their function, respectively of storing energy and producing heat. A growing body of evidence suggests that the reason for such anatomical arrangement is their plasticity, which under appropriate stimulation allows direct conversion of one cell type into the other. In conditions of chronic cold exposure white-to-brown conversion meets the need for thermogenesis, whereas an obesogenic diet induces brown-to-white conversion to meet the need for storing energy. White-to-brown transdifferentiation is of medical interest, because the brown phenotype of the adipose organ is associated to obesity resistance, and drugs inducing this phenotype curb murine obesity and related disorders. Type 2 diabetes is the most common disorder associated to visceral obesity. Macrophages infiltrating the adipose organ are responsible for the low-grade chronic inflammation related to the removal of dead adipocytes, which leads to insulin resistance and T2 diabetes. Adipocyte death is closely related to their growth up to the critical death size. The critical death size of visceral adipocytes is smaller than that of subcutaneous adipocytes, likely accounting for the greater morbidity related to visceral fat. PMID:21254898

  4. Estrogen Receptor α and β in Mouse: Adipose-Derived Stem Cell Proliferation, Migration, and Brown Adipogenesis In Vitro

    Directory of Open Access Journals (Sweden)

    Wentian Zhang

    2016-05-01

    Full Text Available Background/Aims: Adipose-derived stem cells (ASCs belong to mesenchymal stem cells and may play a potential role as seeding cells in stem cell transplantation. To be able to exploit stem cells as therapeutic tool, their defects in some important cellular functions, such as low survival rate and cellular activity, should be considered. This is especially the case for stem cells that are intended for transplantation. Of note, stem cell responses to hormones should be considered since estrogen is known to play a critical role in stem cell behavior. However, different impacts of the estrogen receptor (ER types α and β have not been fully determined in ASC function. In this study, we investigated effects of ERα and ERβ on ASC proliferation, migration, as well as in adipogenesis. Methods: ASCs obtained from mice were cultured with 100nM ERα or ERβ agonist PPT and DPN, respectively. The ERα and ERβ antagonist ICI 182,780 (100nM was used as control. Results: Compared to ERβ, ERα appears more potent in improving ASC proliferation and migration. Investigation of adipogenesis revealed that ERβ played a significant role in suppressing ASC-mediated brown tissue adipogenesis which is in contrast to ERα. These results correlated with reduced mRNA expression of UCP-1, PGC-1α and PPAR-γ. Conclusions: ERα plays a more critical role in promoting ASC proliferation and migration while ERβ is more potent in suppressing ASC brown adipose tissue differentiation mediated by decreased UCP-1, PGC-1α and PPAR-γ expression.

  5. Chronic high-fat diet in fathers programs ß-cell dysfunction in female rat offspring

    DEFF Research Database (Denmark)

    Ng, Sheau-Fang; Lin, Ruby C Y; Laybutt, D Ross;

    2010-01-01

    The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet......-induced maternal obesity on adiposity and metabolism in offspring are well established, the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs ß-cell 'dysfunction' in rat F(1...

  6. FAT10 is associated with the malignancy and drug resistance of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Xue F

    2016-07-01

    Full Text Available Feng Xue,1,2,* Lin Zhu,3,* Qing-wei Meng,1 Liyan Wang,2 Xue-song Chen,1 Yan-bin Zhao,1 Ying Xing,1 Xiao-yun Wang,1 Li Cai1 1The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, 2Department of Medical Oncology, Heilongjiang Provincial Hospital, 3Department of Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China *These authors contributed equally to this work Abstract: Lung cancer has become one of the leading causes of cancer mortality worldwide, and non-small-cell lung cancer (NSCLC accounts for ~85% of all lung cancer cases. Currently, platinum-based chemotherapy drugs, including cisplatin and carboplatin, are the most effective treatment for NSCLC. However, the clinical efficacy of chemotherapy is markedly reduced later in the treatment because drug resistance develops during the treatment. Recently, a series of studies has suggested the involvement of FAT10 in the development and malignancy of multiple cancer types. In this study, we focused our research on the function of FAT10 in NSCLC, which has not been previously reported in the literature. We found that the expression levels of FAT10 were elevated in quick chemoresistance NSCLC tissues, and we demonstrated that FAT10 promotes NSCLC cell proliferation, migration, and invasion. Furthermore, the protein levels of FAT10 were elevated in cisplatin- and carboplatin-resistant NSCLC cells, and knockdown of FAT10 reduced the drug resistance of NSCLC cells. In addition, we gained evidence that FAT10 regulates NSCLC malignancy and drug resistance by modulating the activity of the nuclear factor kappa B signaling pathway. Keywords: FAT10, NSCLC, malignancy, drug resistance, NFκB

  7. Renal cell carcinoma containing macroscopic fat on CT mimics an angiomyolipoma due to bone metaplasia without macroscopic calcification

    OpenAIRE

    Richmond, L; M. Atri; Sherman, C; Sharir, S

    2010-01-01

    We report a case of renal cell carcinoma (RCC) containing foci of macroscopic fat, which were pathologically proven to be areas of osseous metaplasia. The macroscopic fat was not associated with calcification on the pre-operative CT scan. To our knowledge, there are no reported cases of RCC that contain osseous metaplasia without evidence of macroscopic calcification on CT. The finding is significant because standard imaging practice is to classify a renal mass containing intratumoral macrosc...

  8. Testosterone replacement alters the cell size in visceral fat but not in subcutaneous fat in hypogonadal aged male rats as a late-onset hypogonadism animal model

    Directory of Open Access Journals (Sweden)

    Abdelhamed A

    2015-03-01

    Full Text Available Amr Abdelhamed,1,2 Shin-ichi Hisasue,1 Masato Shirai,3 Kazuhito Matsushita,1 Yoshiaki Wakumoto,1 Akira Tsujimura,1 Taiji Tsukamoto,4 Shigeo Horie1 1Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo, Japan; 2Department of Dermatology, Venereology and Andrology, Sohag University, Graduate School of Medicine, Sohag, Egypt; 3Department of Urology, Juntendo University Urayasu Hospital, Urayasu, Japan; 4Department of Urology, School of Medicine, Sapporo Medical University, Sapporo, Japan Background: Patients with late-onset hypogonadism (LOH benefit from testosterone replacement by improvement in the parameters of the metabolic syndrome, but fat cell morphology in these patients is still unclear. This study aims to determine the effect of testosterone replacement on the morphology of fat cells in subcutaneous and visceral adipose tissue and on erectile function in hypogonadal aged male rats as a model of LOH. Methods: Ten male Sprague-Dawley rats aged 20–22 months were randomly allocated to two groups, ie, aged male controls (control group, n=5 and aged males treated with testosterone replacement therapy (TRT group, n=5. Testosterone enanthate 25 mg was injected subcutaneously every 2 weeks for 6 weeks. At 6 weeks, the intracavernous pressure (ICP and mean arterial blood pressure (MAP ratio was assessed. Visceral and subcutaneous adipose tissue specimens were collected and analyzed using Image-J software. Results: Body weight at 2, 4, and 6 weeks after TRT was 800.0±35.4 g, 767.5±46.3 g, and 780±40.4 g, respectively (not statistically significant. The ICP/MAP ratio was 0.341±0.015 in the TRT group and 0.274±0.049 in the control group (not statistically significant. The median subcutaneous fat cell size was 4.85×103 (range 0.85–12.53×103 µm2 in the control group and 4.93×103 (range 6.42–19.7×103 µm2 in the TRT group (not statistically significant. In contrast, median visceral fat cell size was significantly

  9. Uptake and clearance of /sup 238/Pu from liver cells transplanted into fat pads of Fischer-344 rats

    International Nuclear Information System (INIS)

    This research is directed toward understanding the role of liver cell, organ, and environment in Pu biokinetics. Liver cells were isolated from F-344 rats, injected into fat pads, and allowed 21 days to from cellular colonies. Animals injected with liver cells and control animals received a single intraperitoneal injection of 1 μCi /sup 238/Pu citrate and were serially sacrificed 1, 5, 10, 15, 30, and 60 days after injection. Retention kinetics and distribution of Pu in liver and in liver cells growing in fat pads were determined by both radiochemical measurements and autoradiographic techniques. From these measurements, the half-life of Pu in whole liver was estimated to be about 10 days. There were an average of 0.54 and 0.13 tracks/cell in liver cells at 1 and 30 days after injection, respectively. Liver cells in fat pads contained 0.20 and 0.07 tracks/cell at 1 and 30 days or about 1/3 of the initial concentration of Pu observed in liver. From these studies, it was demonstrated that liver cells placed in a foreign environment contain the information needed to recognize and take up Pu and that they also clear Pu. This model may provide a tool to study the uptake and clearance of Pu from human cells growth in fat pads of nude mice

  10. Efficient production of omega-3 fatty acid desaturase (sFat-1)-transgenic pigs by somatic cell nuclear transfer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Omega-3(ω-3) fatty acid desaturase transgenic pigs may improve carcass fatty acid composition. The use of transgenic pigs is also an excellent large animal model for studying the role of ω-3 fatty acids in the prevention and treatment of coronary heart disease and cancer. Transgenic pigs carrying synthesized fatty acid desaturase-1 gene (sFat-1) from Caenorhabditis briggsae by somatic cell nuclear transfer (SCNT) were produced for the first time in China. Porcine fetal fibroblast cells were transfected with a sFat-1 expression cassette by the liposome-mediated method. Transgenic embryos were reconstructed by nuclear transfer of positive cells into enucleated in vitro matured oocytes. A total of 1889 reconstructed embryos were transferred into 10 naturally cycling gilts. Nine early pregnancies were established, 7 of which went to term. Twenty-one piglets were born. The cloning efficiency was 1.1% (born piglets/transferred embryos). The integration of the sFat-1 gene was confirmed in 15 live cloned piglets by PCR and Southern blot except for 2 piglets. Expression of the sFat-1 gene in 12 of 13 piglets was detected with RT-PCR. The data demonstrates that an efficient system for sFat-1 transgenic cloned pigs was developed, which led to the successful production of piglets expressing the sFat-1 gene.

  11. The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice

    Directory of Open Access Journals (Sweden)

    Kopecky Jan

    2011-08-01

    Full Text Available Abstract Background Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA of marine origin exert multiple beneficial effects on health. Our previous study in mice showed that reduction of adiposity by LC n-3 PUFA was associated with both, a shift in adipose tissue metabolism and a decrease in tissue cellularity. The aim of this study was to further characterize the effects of LC n-3 PUFA on fat cell proliferation and differentiation in obese mice. Methods A model of inducible and reversible lipoatrophy (aP2-Cre-ERT2 PPARγL2/L2 mice was used, in which the death of mature adipocytes could be achieved by a selective ablation of peroxisome proliferator-activated receptor γ in response to i.p. injection of tamoxifen. Before the injection, obesity was induced in male mice by 8-week-feeding a corn oil-based high-fat diet (cHF and, subsequently, mice were randomly assigned (day 0 to one of the following groups: (i mice injected by corn-oil-vehicle only, i.e."control" mice, and fed cHF; (ii mice injected by tamoxifen in corn oil, i.e. "mutant" mice, fed cHF; (iii control mice fed cHF diet with15% of dietary lipids replaced by LC n-3 PUFA concentrate (cHF+F; and (iv mutant mice fed cHF+F. Blood and tissue samples were collected at days 14 and 42. Results Mutant mice achieved a maximum weight loss within 10 days post-injection, followed by a compensatory body weight gain, which was significantly faster in the cHF as compared with the cHF+F mutant mice. Also in control mice, body weight gain was depressed in response to dietary LC n-3 PUFA. At day 42, body weights in all groups stabilized, with no significant differences in adipocyte size between the groups, although body weight and adiposity was lower in the cHF+F as compared with the cHF mice, with a stronger effect in the mutant than in control mice. Gene expression analysis documented depression of adipocyte maturation during the reconstitution of adipose tissue in the cHF+F mutant mice. Conclusion

  12. Cell mechanisms of gustatory lipids perception and modulation of the dietary fat preference.

    Science.gov (United States)

    Dramane, Gado; Akpona, Simon; Besnard, Philippe; Khan, Naim A

    2014-12-01

    Dietary lipids are usually responsible of several metabolic disorders. Recent compelling evidences suggest that there is a sixth taste modality, destined for the detection of oro-gustatory fats. The lipid-binding glycoprotein CD36, expressed by circumvallate papillae (CVP) of the mouse tongue, has been shown to be implicated in oro-gustatory perception of dietary lipids. We demonstrate that linoleic acid (LA) by activating sPLA2, cPLA2 and iPLA2 via CD36, produced arachidonic acid (AA) and lyso-phosphatidylcholine (Lyso-PC) which triggered Ca(2+) influx in CD36-positive taste bud cells (TBC), purified from mouse CVP. LA induced the production of Ca(2+) influx factor (CIF). CIF, AA and Lyso-PC exerted different actions on the opening of store-operated Ca2+ (SOC) channels, constituted of Orai proteins and regulated by STIM1, a sensor of Ca(2+) depletion in the endoplasmic reticulum. We observed that CIF and Lyso-PC opened Orai1 channels whereas AA-opened Ca(2+) channels were composed of Orai1/Orai3. STIM1 was found to regulate LA-induced CIF production and opening of both kinds of Ca(2+) channels. Furthermore, Stim1(-/-) mice lost the spontaneous preference for fat, observed in wild-type animals. Our results suggest that fatty acid-induced Ca(2+) signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat. Other cell types are involved in, and external factors can influence this preference.

  13. Cell mechanisms of gustatory lipids perception and modulation of the dietary fat preference.

    Science.gov (United States)

    Dramane, Gado; Akpona, Simon; Besnard, Philippe; Khan, Naim A

    2014-12-01

    Dietary lipids are usually responsible of several metabolic disorders. Recent compelling evidences suggest that there is a sixth taste modality, destined for the detection of oro-gustatory fats. The lipid-binding glycoprotein CD36, expressed by circumvallate papillae (CVP) of the mouse tongue, has been shown to be implicated in oro-gustatory perception of dietary lipids. We demonstrate that linoleic acid (LA) by activating sPLA2, cPLA2 and iPLA2 via CD36, produced arachidonic acid (AA) and lyso-phosphatidylcholine (Lyso-PC) which triggered Ca(2+) influx in CD36-positive taste bud cells (TBC), purified from mouse CVP. LA induced the production of Ca(2+) influx factor (CIF). CIF, AA and Lyso-PC exerted different actions on the opening of store-operated Ca2+ (SOC) channels, constituted of Orai proteins and regulated by STIM1, a sensor of Ca(2+) depletion in the endoplasmic reticulum. We observed that CIF and Lyso-PC opened Orai1 channels whereas AA-opened Ca(2+) channels were composed of Orai1/Orai3. STIM1 was found to regulate LA-induced CIF production and opening of both kinds of Ca(2+) channels. Furthermore, Stim1(-/-) mice lost the spontaneous preference for fat, observed in wild-type animals. Our results suggest that fatty acid-induced Ca(2+) signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat. Other cell types are involved in, and external factors can influence this preference. PMID:24997404

  14. Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPδ.

    Science.gov (United States)

    Armengol, Jordi; Villena, Josep A; Hondares, Elayne; Carmona, María C; Sul, Hei Sook; Iglesias, Roser; Giralt, Marta; Villarroya, Francesc

    2012-05-01

    Pref-1 (pre-adipocyte factor-1) is known to play a central role in regulating white adipocyte differentiation, but the role of Pref-1 in BAT (brown adipose tissue) has not been analysed. In the present study we found that Pref-1 expression is high in fetal BAT and declines progressively after birth. However, Pref-1-null mice showed unaltered fetal development of BAT, but exhibited signs of over-activation of BAT thermogenesis in the post-natal period. In C/EBP (CCAAT/enhancer-binding protein) α-null mice, a rodent model of impaired fetal BAT differentiation, Pref-1 was dramatically overexpressed, in association with reduced expression of the Ucp1 (uncoupling protein 1) gene, a BAT-specific marker of thermogenic differentiation. In brown adipocyte cell culture models, Pref-1 was mostly expressed in pre-adipocytes and declined with brown adipocyte differentiation. The transcription factor C/EBPδ activated the Pref-1 gene transcription in brown adipocytes, through binding to the proximal promoter region. Accordingly, siRNA (small interfering RNA)-induced C/EBPδ knockdown led to reduced Pref-1 gene expression. This effect is consistent with the observed overexpression of C/EBPδ in C/EBPα-null BAT and high expression of C/EBPδ in brown pre-adipocytes. Dexamethasone treatment of brown pre-adipocytes suppressed Pref-1 down-regulation occurring throughout the brown adipocyte differentiation process, increased the expression of C/EBPδ and strongly impaired expression of the thermogenic markers UCP1 and PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-α]. However, it did not alter normal fat accumulation or expression of non-BAT-specific genes. Collectively, these results specifically implicate Pref-1 in controlling the thermogenic gene expression program in BAT, and identify C/EBPδ as a novel transcriptional regulator of Pref-1 gene expression that may be related to the specific role of glucocorticoids in BAT differentiation.

  15. The role of brown adipose tissue in temperature regulation. [of hibernating and hypothermic mammals

    Science.gov (United States)

    Smith, R. E.

    1973-01-01

    The thermogenetic capacities of brown adipose tissue were studied on marmots, rats and monkeys in response to cold exposure. All experiments indicated that the brown fat produced heat and slowed the cooling of tissues.

  16. Biomimetic fat cell (BFC) modification and for lindane removal from aqueous solution.

    Science.gov (United States)

    Liyan, Song; Youcai, Zhao; Guojian, Wang; Bing, Li; Dongjie, Niu; Xiaoli, Chai

    2008-03-01

    To improve the regeneration ability of biomimetic fat cell (BFC), an innovative agent for hydrophobic organic contaminants (HOCs) removal, BFC was modified through introducing 1, 3, 5-benzenetricarboxyl trichloride with trifunctional group and heterocyclic piperazine in this research. Modified biomimetic fat cell (MBFC) has a good lindane removal capacity close to that of BFC and powder activated carbon (PAC), and the lindane removal is 97.68, 96.65 and 98.36% with 7 mg/L lindane initial concentration, respectively. At the same time, 20 mg/L MBFC or PAC is sufficient for 10 microg/L lindane removal, and in 20-60 mg/L doses range the lindane removal by both MBFC and PAC can reach 99.0%; When the doses is below 10 mg/L, MBFC showed better lindane removal than PAC and MBFC even could reach 96.8% lindane removal in 5 mg/L dose. Lindane removal by MBFC could be held on 95% above in first 6-time reuse. Though the lindane removal by MBFC decreased with the reuse time increasing, MBFC still could remove 80 % lindane after 9 times regeneration. In contract with BFC, MBFC showed obvious advantage on the regeneration. The lindane removal mechanism by MBFC, similar with BFC, includes bioaccumulation by MBFC nucleolus-triolein and adsorption by MBFC membrane, and the bioaccumulation is the main way.

  17. Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease.

    Science.gov (United States)

    Burke, Shoshana; Nagajyothi, Fnu; Thi, Mia M; Hanani, Menachem; Scherer, Philipp E; Tanowitz, Herbert B; Spray, David C

    2014-11-01

    Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions.

  18. Calcitriol enhances fat synthesis factors and calpain activity in co-cultured cells.

    Science.gov (United States)

    Choi, Hyuck; Myung, Kyuho

    2014-08-01

    We have conducted an in vitro experiment to determine whether calcitriol can act as a fat synthesizer and/or meat tenderizer when skeletal muscle cells, adipose tissue, and macrophages are co-cultured. When co-cultured, pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression increased, whereas decreased anti-inflammatory cytokine (IL-10 and IL-15) expression decreased in both C2C12 and 3T3-L1 cells. Calcitriol increased reactive oxygen species (ROS) production in the media. While adiponectin gene expression decreased, leptin, resistin, CCAAT-enhancer-binding protein-beta (C/EBP-β), and peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression was significantly (P meat tenderizer, in meat-producing animals. PMID:24687633

  19. Phenotypic and Functional Properties of Porcine Dedifferentiated Fat Cells during the Long-Term Culture In Vitro

    OpenAIRE

    Xuewu Peng; Tongxing Song; Xiaoming Hu; Yuanfei Zhou; Hongkui Wei; Jian Peng; Siwen Jiang

    2015-01-01

    It has been proved that terminally differentiated mature adipocytes possess abilities to dedifferentiate into fibroblast-like progeny cells with self-renewal and multiple differentiation, termed dedifferentiated fat (DFAT) cells. However, the biological properties of DFAT cells during long-term culture in vitro have not been elucidated. Here, we obtained fibroblast-like morphology of porcine DFAT cells by ceiling culture. During the dedifferentiation process, round mature adipocytes with sing...

  20. CDP-diacylglycerol synthetase coordinates cell growth and fat storage through phosphatidylinositol metabolism and the insulin pathway.

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2014-03-01

    Full Text Available During development, animals usually undergo a rapid growth phase followed by a homeostatic stage when growth has ceased. The increase in cell size and number during the growth phase requires a large amount of lipids; while in the static state, excess lipids are usually stored in adipose tissues in preparation for nutrient-limited conditions. How cells coordinate growth and fat storage is not fully understood. Through a genetic screen we identified Drosophila melanogaster CDP-diacylglycerol synthetase (CDS/CdsA, which diverts phosphatidic acid from triacylglycerol synthesis to phosphatidylinositol (PI synthesis and coordinates cell growth and fat storage. Loss of CdsA function causes significant accumulation of neutral lipids in many tissues along with reduced cell/organ size. These phenotypes can be traced back to reduced PI levels and, subsequently, low insulin pathway activity. Overexpressing CdsA rescues the fat storage and cell growth phenotypes of insulin pathway mutants, suggesting that CdsA coordinates cell/tissue growth and lipid storage through the insulin pathway. We also revealed that a DAG-to-PE route mediated by the choline/ethanolamine phosphotransferase Bbc may contribute to the growth of fat cells in CdsA RNAi.

  1. Single-cell transcriptomics and functional target validation of brown adipocytes show their complex roles in metabolic homeostasis.

    Science.gov (United States)

    Spaethling, Jennifer M; Sanchez-Alavez, Manuel; Lee, JaeHee; Xia, Feng C; Dueck, Hannah; Wang, Wenshan; Fisher, Stephen A; Sul, Jai-Yoon; Seale, Patrick; Kim, Junhyong; Bartfai, Tamas; Eberwine, James

    2016-01-01

    Brown adipocytes (BAs) are specialized for adaptive thermogenesis and, upon sympathetic stimulation, activate mitochondrial uncoupling protein (UCP)-1 and oxidize fatty acids to generate heat. The capacity for brown adipose tissue (BAT) to protect against obesity and metabolic disease is recognized, yet information about which signals activate BA, besides β3-adrenergic receptor stimulation, is limited. Using single-cell transcriptomics, we confirmed the presence of mRNAs encoding traditional BAT markers (i.e., UCP1, expressed in 100% of BAs Adrb3, expressed in 1000-fold) in their expression at both the mRNA and protein levels. We further identified mRNAs encoding novel markers, orphan GPCRs, and many receptors that bind the classic neurotransmitters, neuropeptides, chemokines, cytokines, and hormones. The transcriptome variability between BAs suggests a much larger range of responsiveness of BAT than previously recognized and that not all BAs function identically. We examined the in vivo functional expression of 12 selected receptors by microinjecting agonists into live mouse BAT and analyzing the metabolic response. In this manner, we expanded the number of known receptors on BAs at least 25-fold, while showing that the expression of classic BA markers is more complex and variable than previously thought. PMID:26304220

  2. Use of rat mature adipocyte-derived dedifferentiated fat cells as a cell source for periodontal tissue regeneration

    Directory of Open Access Journals (Sweden)

    Daisuke eAkita

    2016-02-01

    Full Text Available Lipid-free fibroblast-like cells, known as dedifferentiated fat (DFAT cells, can be generated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and can transdifferentiate into various cell types under appropriate culture conditions. The first objective of this study was to compare the multilineage differentiation potential of DFAT cells with that of adipose-derived stem cells (ASCs on mesenchymal stem cellsWe obtained DFAT cells and ASCs from inbred rats and found that rat DFAT cells possess higher osteogenic differentiation potential than rat ASCs. On the other hand, DFAT cells show similar adipogenic differentiation, and chondrogenic differentiation potential in comparison with ASCs. The second objective of this study was to assess the regenerative potential of DFAT cells combined with novel solid scaffolds composed of PLGA (Poly d, l-lactic-co-glycolic acid on periodontal tissue, and to compare this with the regenerative potential of ASCs combined with PLGA scaffolds. Cultured DFAT cells and ASCs were seeded onto PLGA scaffolds (DFAT/PLGA and ASCs/PLGA and transplanted into periodontal fenestration defects in rat mandible. Micro computed tomography analysis revealed a significantly higher amount of bone regeneration in the DFAT/PLGA group compared with that of ASCs/PLGA and PLGA-alone groups at 2, 3 and 5 weeks after transplantation. Similarly, histomorphometric analysis showed that DFAT/PLGA groups had significantly greater width of cementum, periodontal ligament and alveolar bone than ASCs/PLGA and PLGA-alone groups. In addition, transplanted fluorescent-labeled DFAT cells were observed in the periodontal ligament beside the newly formed bone and cementum. These findings suggest that DFAT cells have a greater potential for enhancing periodontal tissue regeneration than ASCs. Therefore, DFAT cells are a promising cell source for periodontium regeneration.

  3. Effects of Spinach Powder Fat-Soluble Extract on Proliferation of Human Gastric Adenocarcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    HE TAo; HUANG CHENG-YU; CHEN HAl; HOU YUN-HUA

    1999-01-01

    Four kinds of assays were used to study the effect of a fat-soluble extract of spinach powder(SPFE) on the proliferation of human gastric adenocarcinoma cell line (SGC-7901) in vitro.These studies included: ( i ) cell growth assay, ( ii ) colony forming assay, ( iii ) MTT colorimetric assay, and ( iv ) 3H-TdR incorporation assay. The concentrations of SPFE expressed as the level of β-carotene in the medium were 2 × 10-s, 2 × 10-7 and 2 × 10-6 mol/L β-carotene in assays ( i ) ~ ( iii ), but 4 × 10-8, 4 × 10-7 and 4 × 10-6 mol/L β-carotene in assay ( iV ) respectively. The results indicated that SPFE inhibited the proliferation and colony forming ability of SGC-7901 cells. And in MTT assay, SPFE inhibited the viability of SGC-7901 cells, but no inhibitory effect of SPFE was observed on the viability of lymphocytes in peripheral blood of healthy people. Finally, in the 3H-TdR incorporation test, both SPFE and β-carotene showed significant inhibitory effects on DNA synthesis in SGC-7901 cells, but SPFE was more effective than 3-carotene.

  4. High ω3-polyunsaturated fatty acids in fat-1 mice prevent streptozotocin-induced Purkinje cell degeneration through BDNF-mediated autophagy

    OpenAIRE

    Dong Ho Bak; Enji Zhang; Min-Hee Yi; Do-Kyung Kim; Kyu Lim; Jwa-Jin Kim; Dong Woon Kim

    2015-01-01

    Loss of Purkinje cells has been implicated in the development of diabetic neuropathy, and this degeneration is characterized by impairment of autophagic processes. We evaluated whether fat-1 transgenic mice, a well-established animal model that endogenously synthesizes ω3 polyunsaturated fatty acids (ω3-PUFA), are protected from Purkinje cell degeneration in streptozotocin (STZ)-treated model with fat-1 mice. STZ-treated fat-1 mice did not develop hyperglycemia, motor deficits, or Purkinje ce...

  5. Mechanisms of fat-induced gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide secretion from K cells.

    Science.gov (United States)

    Yamane, Shunsuke; Harada, Norio; Inagaki, Nobuya

    2016-04-01

    Gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which are gastrointestinal hormones released in response to nutrient ingestion and potentiate glucose-stimulated insulin secretion. Single fat ingestion stimulates GIP secretion from enteroendocrine K cells; chronic high-fat diet (HFD) loading enhances GIP secretion and induces obesity in mice in a GIP-dependent manner. However, the mechanisms of GIP secretion from K cells in response to fat ingestion and GIP hypersecretion in HFD-induced obesity are not well understood. We generated GIP-green fluorescent protein knock-in (GIP (gfp/+)) mice, in which K cells are labeled by enhanced GIP-green fluorescent protein. Microarray analysis of isolated K cells from GIP (gfp/+) mice showed that both fatty acid-binding protein 5 and G protein-coupled receptor 120 are highly expressed in K cells. Single oral administration of fat resulted in significant reduction of GIP secretion in both fatty acid-binding protein 5- and G protein-coupled receptor 120-deficient mice, showing that fatty acid-binding protein 5 and G protein-coupled receptor 120 are involved in acute fat-induced GIP secretion. Furthermore, the transcriptional factor, regulatory factor X6 (Rfx6), is highly expressed in K cells. In vitro experiments using the mouse enteroendocrine cell line, STC-1, showed that GIP messenger ribonucleic acid levels are upregulated by Rfx6. Expression levels of Rfx6 messenger ribonucleic acid as well as that of GIP messenger ribonucleic acid were augmented in the K cells of HFD-induced obese mice, in which GIP content in the small intestine is increased compared with that in lean mice fed a control diet. These results suggest that Rfx6 is involved in hypersecretion of GIP in HFD-induced obese conditions by increasing GIP gene expression. PMID:27186351

  6. Fermented Brown Rice Extract Causes Apoptotic Death of Human Acute Lymphoblastic Leukemia Cells via Death Receptor Pathway.

    Science.gov (United States)

    Horie, Yukiko; Nemoto, Hideyuki; Itoh, Mari; Kosaka, Hiroaki; Morita, Kyoji

    2016-04-01

    Mixture of brown rice and rice bran fermented with Aspergillus oryzae, designated as FBRA, has been reported to reveal anti-carcinogenic and anti-inflammatory effects in rodents. Then, to test its potential anti-cancer activity, the aqueous extract was prepared from FBRA powder, and the effect of this extract on human acute lymphoblastic leukemia Jurkat cells was directly examined. The exposure to FBRA extract reduced the cell viability in a concentration- and time-dependent manner. The reduction of the cell viability was accompanied by the DNA fragmentation, and partially restored by treatment with pan-caspase inhibitor. Further studies showed that FBRA extract induced the cleavage of caspase-8, -9, and -3, and decreased Bcl-2 protein expression. Moreover, the expression of tBid, DR5, and Fas proteins was enhanced by FBRA extract, and the pretreatment with caspase-8 inhibitor, but not caspase-9 inhibitor, restored the reduction of the cell viability induced by FBRA extract. These findings suggested that FBRA extract could induce the apoptotic death of human acute lymphoblastic leukemia cells probably through mainly the death receptor-mediated pathway and supplementarily through the tBid-mediated mitochondrial pathway, proposing the possibility that FBRA was a potential functional food beneficial to patients with hematological cancer. PMID:26769704

  7. Dynamic changes in lipid droplet-associated proteins in the "browning" of white adipose tissues.

    Science.gov (United States)

    Barneda, David; Frontini, Andrea; Cinti, Saverio; Christian, Mark

    2013-05-01

    The morphological and functional differences between lipid droplets (LDs) in brown (BAT) and white (WAT) adipose tissues will largely be determined by their associated proteins. Analysing mRNA expression in mice fat depots we have found that most LD protein genes are expressed at higher levels in BAT, with the greatest differences observed for Cidea and Plin5. Prolonged cold exposure, which induces the appearance of brown-like adipocytes in mice WAT depots, was accompanied with the potentiation of the lipolytic machinery, with changes in ATGL, CGI-58 and G0S2 gene expression. However the major change detected in WAT was the enhancement of Cidea mRNA. Together with the increase in Cidec, it indicates that LD enlargement through LD-LD transference of fat is an important process during WAT browning. To study the dynamics of this phenotypic change, we have applied 4D confocal microscopy in differentiated 3T3-L1 cells under sustained β-adrenergic stimulation. Under these conditions the cells experienced a LD remodelling cycle, with progressive reduction on the LD size by lipolysis, followed by the formation of new LDs, which were subjected to an enlargement process, likely to be CIDE-triggered, until the cell returned to the basal state. This transformation would be triggered by the activation of a thermogenic futile cycle of lipolysis/lipogenesis and could facilitate the molecular mechanism for the unilocular to multilocular transformation during WAT browning. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  8. Brown seaweed pigment as a dye source for photoelectrochemical solar cells

    Science.gov (United States)

    Calogero, Giuseppe; Citro, Ilaria; Di Marco, Gaetano; Armeli Minicante, Simona; Morabito, Marina; Genovese, Giuseppa

    2014-01-01

    Chlorophylls based-dyes obtained from seaweeds represent attractive alternatives to the expensive and polluting pyridil based Ru complexes because of their abundance in nature. Another important characteristic is that the algae do not subtract either cropland or agricultural water, therefore do not conflict with agro-food sector. This pigment shows a typical intense absorption in the UV/blue (Soret band) and a less intense band in the red/near IR (Q band) spectral regions and for these reasons appear very promising as sensitizer dyes for DSSC. In the present study, we utilized chlorophylls from samples of the brown alga Undaria pinnatifida as sensitizer in DSSCs. The dye, extracted by frozen seaweeds and used without any chemical purification, showed a very good fill factor (0.69). Even the photelectrochemical parameters if compared with the existent literature are very interesting.

  9. The Drosophila Cadherin Fat regulates tissue size and planar cell polarity through different domains.

    Directory of Open Access Journals (Sweden)

    Xuesong Zhao

    Full Text Available The Drosophila Cadherin Fat (Ft has been identified as a crucial regulator of tissue size and Planar Cell Polarity (PCP. However, the precise mechanism by which Ft regulates these processes remains unclear. In order to advance our understanding of the action of Ft, we have sought to identify the crucial Ft effector domains. Here we report that a small region of the Ft cytoplasmic domain (H2 region is both necessary and sufficient, when membrane localized, to support viability and prevent tissue overgrowth. Interestingly, the H2 region is dispensable for regulating PCP signaling, whereas the mutant Ft lacking the H2 region is fully capable of directing PCP. This result suggests that Ft's roles in PCP signaling and tissue size control are separable, and each can be carried out independently. Surprisingly, the crucial regions of Ft identified in our structure-function study do not overlap with the previously reported interaction regions with Atrophin, Dco, or Lowfat.

  10. Immunomagnetic Separation of Fat Depot-Specific Sca1high Adipose-Derived Stem Cells (Ascs)

    Science.gov (United States)

    Barnes, Richard H; Chun, Tae-Hwa

    2016-01-01

    The isolation of adipose-derived stem cells (ASCs) is an important method in the field of adipose tissue biology, adipogenesis, and extracellular matrix (ECM) remodeling. In vivo, ECM-rich environment consisting of fibrillar collagens provides a structural support to adipose tissues during the progression and regression of obesity. Physiological ECM remodeling mediated by matrix metalloproteinases (MMPs) plays a major role in regulating adipose tissue size and function1, 2. The loss of physiological collagenolytic ECM remodeling may lead to excessive collagen accumulation (tissue fibrosis), macrophage infiltration, and ultimately, a loss of metabolic homeostasis including insulin resistance3, 4. When a phenotypic change of the adipose tissue is observed in gene-targeted mouse models, isolating primary ASCs from fat depots for in vitro studies is an effective approach to define the role of the specific gene in regulating the function of ASCs. In the following, we define an immunomagnetic separation of Sca1high ASCs. PMID:27583550

  11. Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds Inhibit Proliferation of Melanoma Cells and Induce Apoptosis by Activation of Caspase-3 in Vitro

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu;

    2011-01-01

    Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds, especially brown macro-algae, are known to possess essential bioactive properties, notably growth inhibitory effects on tumor cells. In this work, we conducted a series of in vitro studies to examine the influence of FCSPs...

  12. Determination of the Effects of Some Environmental Factors on Raw Milk Somatic Cell Count of Brown Swiss Cows Raised in Farmer Condition

    OpenAIRE

    Aziz Şahin; Muzaffer Kaşıkcı

    2015-01-01

    In the current research, it was aimed to determine Somatic Cell Count (SCC) and the factors effecting on SCC in milk samples of Brown Swiss cattle raised at different farm conditions in Yıldızeli district of Sivas province in Turkey. Raw milk samples were collected at morning milking in months of May and November in year 2012. In total, 244 milk samples from 122 Brown Swiss cattle were analyzed. The effects of calving age, farm and test month on SCC were statistically significant. In the pres...

  13. M1-M2 balancing act in white adipose tissue browning - a new role for RIP140.

    Science.gov (United States)

    Liu, Pu-Ste; Lin, Yi-Wei; Burton, Frank H; Wei, Li-Na

    2015-01-01

    A "Holy Grail" sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophages that migrate into adipose deposits. The coregulator, Receptor Interacting Protein 140 (RIP140), plays a key role in regulating this communication. In mice on a high-fat diet, the level of RIP140 in macrophages is dramatically elevated to activate their inflammatory M1 polarization and enhance their recruitment into WAT, facilitating IR. Conversely, lowering the level of RIP140 in macrophages not only reduces M1 macrophages but also expands alternatively polarized, anti-inflammatory M2 macrophages, triggering white adipose tissue browning, fat burning, and restoration of insulin sensitivity. This suggests a potential therapeutic strategy for reversing IR, obesity, and atherosclerotic or even cosmetic fat deposits: therapeutic browning of white adipose deposits by diminishing RIP140 levels in macrophages.

  14. Identification of an anticancer compound against HT-29 cells from Phellinus linteus grown on germinated brown rice

    Institute of Scientific and Technical Information of China (English)

    Tae-Il Jeon; Chang-Hwa Jung; Jeong-Yong Cho; Dong Ki Park; Jae-Hak Moon

    2013-01-01

    Objective:To isolate and identify the anticancer compound against proliferation of human colon cancer cells from ethyl acetate (EtOAc) extract of Phellinus linteus grown on germinated brown rice (PB). Methods: EtOAc extract of PB was partitioned with n-hexane, EtOAc, and water-saturated n-butanol. Anticancer compound of n-hexane layer was isolated and identified by HPLC and NMR, respectively. Cytotoxicity against HT-29 cells was tested by SRB assay. Results: The n-hexane layer obtained after solvent fractionation of PB EtOAc extracts showed a potent anticancer activity against the HT-29 cell line. Atractylenolide I, a eudesmane-type sesquiterpene lactone, a major anticancer substance of PB, was isolated from the n-hexane layer by silica gel column chromatography and preparative-HPLC. This structure was elucidated by one-and two-dimensional NMR spectroscopic data. Atractylenolide I has not been reported in mushrooms or rice as of yet. The isolated compound dose-dependently inhibited the growth of HT-29 human colon cancer cells. Conclusions:Atractylenolide I might contribute to the anticancer effect of PB.

  15. Anti-Proliferative Activity of Meroditerpenoids Isolated from the Brown Alga Stypopodium flabelliforme against Several Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Patricia Valentao

    2011-05-01

    Full Text Available The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines. Cell lines tested included human colon adenocarcinoma (Caco-2, human neuroblastoma (SH-SY5Y, rat basophilic leukemia (RBL-2H3, murine macrophages (RAW.267 and Chinese hamster fibroblasts (V79. Antimicrobial activity of the compounds was also evaluated against Staphylococcus aureus, Salmonella typhimurium, Proteus mirabilis, Bacillus cereus, Enterococcus faecalis and Micrococcus luteus. Overall, the compounds showed good activity against all cell lines, with SH-SY5Y and RAW.267 being the most susceptible. Antimicrobial capacity was observed for epitaondiol monoacetate, stypotriol triacetate and stypodiol, with the first being the most active. The results suggest that these molecules deserve further studies in order to evaluate their potential as therapeutic agents.

  16. Uptake and clearance of plutonium-238 from intact liver and liver cells transplanted into fat pads of F344/N rats

    International Nuclear Information System (INIS)

    An understanding of the role of liver cells and the intact liver in plutonium biokinetics is needed. Liver cells were isolated from rats, injected into fat pads of recipient rats, and allowed 21 days to form cell colonies. Rats then received a single intraperitoneal injection of 1 μCi 238Pu-citrate and were serially sacrificed. Uptake, retention, and distribution of Pu in intact liver and in liver cells growing in fat pads were determined. Intact liver cells took up about twice as much 238Pu as liver cells transplanted into fat pads. However, the retention kinetics of Pu were similar for both the liver cells in the fat pads and the intact liver cells when the retention was expressed as activity per cell. 4 references, 1 figure, 1 table

  17. Chondrogenesis of human infrapatellar fat pad stem cells on acellular dermal matrix

    Directory of Open Access Journals (Sweden)

    Ken eYe

    2016-01-01

    Full Text Available Acellular dermal matrix (ADM has been in clinical use for decades in numerous surgical applications. The ability for ADM to promote cellular repopulation and revascularisation, and tissue regeneration is well documented. Adipose stem cells have the ability to differentiate into mesenchymal tissue types, including bone and cartilage. The aim of this study was to investigate the potential interaction between ADM and adipose stem cells in vitro using TGFβ3 and BMP6.Human infrapatellar fat pad derived adipose stem cells (IPFP-ASC were cultured with ADM derived from rat dermis under chondrogenic (TGFβ3 and BMP6 in vitro for 2 and 4 weeks. Histology, qPCR and immunohistochemistry were performed to assess for markers of chondrogenesis (collagen Type II, SOX9 and proteoglycans. At 4 weeks, cell-scaffold constructs displayed cellular changes consistent with chondrogenesis, with evidence of stratification of cell layers and development of a hyaline-like cartilage layer superficially which stained positively for collagen Type II and proteoglycans. Significant cell-matrix interaction was seen between the cartilage layer and the ADM itself with seamless integration between each layer. Real time qPCR showed significantly increases of COL2A1, SOX9, and ACAN gene expression over 4 weeks when compared to control. COL1A2 gene expression remained unchanged over 4 weeks.We believe the principles which make ADM versatile and successful for tissue regeneration are application to cartilage regeneration. This study demonstrates in vitro the ability for IPFP-ASCs to undergo chondrogenesis, infiltrate and interact with ADM. These outcomes serve as a platform for in vivo modelling of ADM for cartilage repair.

  18. Chondrogenesis of Human Infrapatellar Fat Pad Stem Cells on Acellular Dermal Matrix.

    Science.gov (United States)

    Ye, Ken; Traianedes, Kathy; Choong, Peter F M; Myers, Damian E

    2016-01-01

    Acellular dermal matrix (ADM) has been in clinical use for decades in numerous surgical applications. The ability for ADM to promote cellular repopulation, revascularisation and tissue regeneration is well documented. Adipose stem cells have the ability to differentiate into mesenchymal tissue types, including bone and cartilage. The aim of this study was to investigate the potential interaction between ADM and adipose stem cells in vitro using TGFβ3 and BMP6. Human infrapatellar fat pad-derived adipose stem cells (IPFP-ASC) were cultured with ADM derived from rat dermis in chondrogenic (TGFβ3 and BMP6) medium in vitro for 2 and 4 weeks. Histology, qPCR, and immunohistochemistry were performed to assess for markers of chondrogenesis (collagen Type II, SOX9 and proteoglycans). At 4 weeks, cell-scaffold constructs displayed cellular changes consistent with chondrogenesis, with evidence of stratification of cell layers and development of a hyaline-like cartilage layer superficially, which stained positively for collagen Type II and proteoglycans. Significant cell-matrix interaction was seen between the cartilage layer and the ADM itself with seamless integration between each layer. Real time qPCR showed significantly increased COL2A1, SOX9, and ACAN gene expression over 4 weeks when compared to control. COL1A2 gene expression remained unchanged over 4 weeks. We believe that the principles that make ADM versatile and successful for tissue regeneration are applicable to cartilage regeneration. This study demonstrates in vitro the ability for IPFP-ASCs to undergo chondrogenesis, infiltrate, and interact with ADM. These outcomes serve as a platform for in vivo modelling of ADM for cartilage repair. PMID:26858950

  19. Determination of the Effects of Some Environmental Factors on Raw Milk Somatic Cell Count of Brown Swiss Cows Raised in Farmer Condition

    Directory of Open Access Journals (Sweden)

    Aziz Şahin

    2015-07-01

    Full Text Available In the current research, it was aimed to determine Somatic Cell Count (SCC and the factors effecting on SCC in milk samples of Brown Swiss cattle raised at different farm conditions in Yıldızeli district of Sivas province in Turkey. Raw milk samples were collected at morning milking in months of May and November in year 2012. In total, 244 milk samples from 122 Brown Swiss cattle were analyzed. The effects of calving age, farm and test month on SCC were statistically significant. In the present study, the average SCC was determined as 1209696±111361 cells/ml. About 56.6% of milk from November month and about 48.4 % of milk samples from Brown Swiss were containing over 500.000 cell/ ml. As a result, Brown Swiss cattle identified SCC in raw milk samples were significantly higher than the values specified in the legislation of the European Union Commission and Turkish Food Codex.

  20. Lipid Droplet Accumulation and Impaired Fat Efflux in Polarized Hepatic Cells: Consequences of Ethanol Metabolism

    Directory of Open Access Journals (Sweden)

    Benita L. McVicker

    2012-01-01

    Full Text Available Steatosis, an early manifestation in alcoholic liver disease, is associated with the accumulation of hepatocellular lipid droplets (LDs. However, the role ethanol metabolism has in LD formation and turnover remains undefined. Here, we assessed LD dynamics following ethanol and oleic acid treatment to ethanol-metabolizing WIF-B cells (a hybrid of human fibroblasts (WI 38 and Fao rat hepatoma cells. An OA dose-dependent increase in triglyceride and stained lipids was identified which doubled (P<0.05 in the presence of ethanol. This effect was blunted with the inclusion of an alcohol metabolism inhibitor. The ethanol/ OA combination also induced adipophilin, LD coat protein involved in the attenuation of lipolysis. Additionally, ethanol treatment resulted in a significant reduction in lipid efflux. These data demonstrate that the metabolism of ethanol in hepatic cells is related to LD accumulation, impaired fat efflux, and enhancements in LD-associated proteins. These alterations in LD dynamics may contribute to ethanol-mediated defects in hepatocellular LD regulation and the formation of steatosis.

  1. Lipid Droplet Accumulation and Impaired Fat Efflux in Polarized Hepatic Cells: Consequences of Ethanol Metabolism

    Science.gov (United States)

    McVicker, Benita L.; Rasineni, Karuna; Tuma, Dean J.; McNiven, Mark A.; Casey, Carol A.

    2012-01-01

    Steatosis, an early manifestation in alcoholic liver disease, is associated with the accumulation of hepatocellular lipid droplets (LDs). However, the role ethanol metabolism has in LD formation and turnover remains undefined. Here, we assessed LD dynamics following ethanol and oleic acid treatment to ethanol-metabolizing WIF-B cells (a hybrid of human fibroblasts (WI 38) and Fao rat hepatoma cells). An OA dose-dependent increase in triglyceride and stained lipids was identified which doubled (P < 0.05) in the presence of ethanol. This effect was blunted with the inclusion of an alcohol metabolism inhibitor. The ethanol/ OA combination also induced adipophilin, LD coat protein involved in the attenuation of lipolysis. Additionally, ethanol treatment resulted in a significant reduction in lipid efflux. These data demonstrate that the metabolism of ethanol in hepatic cells is related to LD accumulation, impaired fat efflux, and enhancements in LD-associated proteins. These alterations in LD dynamics may contribute to ethanol-mediated defects in hepatocellular LD regulation and the formation of steatosis. PMID:22506128

  2. Induction and differentiation of adipose-derived stem cells from human buccal fat pads into salivary gland cells.

    Science.gov (United States)

    Kawakami, Miyuki; Ishikawa, Hiroshi; Tanaka, Akira; Mataga, Izumi

    2016-07-01

    Atrophy or hypofunction of the salivary gland because of aging or disease leads to hyposalivation that affects patient quality of life by causing dry mouth, deterioration of mastication/deglutition, and poor oral hygiene status. Current therapy for atrophy or hypofunction of the salivary gland in clinical practice focuses on symptom relief using drugs and artificial saliva; therefore, there is still a need to develop new therapies. To investigate potential novel therapeutic targets, we induced the differentiation of salivary gland cells by co-culturing human adipose-derived stem cells isolated from buccal fat pads (hBFP-ASCs) with human salivary-gland-derived fibroblasts (hSG-fibros). We examined their potential for transplantation and tissue neogenesis. Following the culture of hBFP-ASCs and hSG-fibros, differentiated cells were transplanted into the submandibular glands of SCID mice, and their degree of differentiation in tissues was determined. We also examined their potential for functional tissue reconstitution using a three-dimensional (3D) culture system. Co-cultured cells expressed salivary-glandrelated markers and generated new tissues following transplantation in vivo. Moreover, cell reconstituted glandular structures in the 3D culture system. In conclusion, coculture of hSG-fibros with hBFP-ASCs led to successful differentiation into salivary gland cells that could be transplanted to generate new tissues. PMID:26842556

  3. Protein kinase A-mediated cell proliferation in brown preadipocytes is independent of Erk1/2, PI{sub 3}K and mTOR

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yanling; Sato, Masaaki; Guo, Yuan; Bengtsson, Tore; Nedergaard, Jan, E-mail: jan@metabol.su.se

    2014-10-15

    The physiological agonist norepinephrine promotes cell proliferation of brown preadipocytes during the process of tissue recruitment. In a primary culture system, cAMP mediates these adrenergic effects. In the present study, we demonstrated that, in contrast to other systems where the mitogenic effect of cAMP requires the synergistic action of (serum) growth factors, especially insulin/IGF, the cAMP effect in brown preadipocytes was independent of serum and insulin. Protein kinase A, rather than Epac, mediated the cAMP mitogenic effect. The Erk 1/2 family of MAPK, the PI{sub 3}K system and the mTOR complexes were all activated by cAMP, but these activations were not necessary for cAMP-induced cell proliferation; a protein kinase C isoform may be involved in mediating cAMP-activated cell proliferation. We conclude that the generally acknowledged cellular mediators for induction of cell proliferation are not involved in this process in the brown preadipocyte system; this conclusion may be of relevance both for examination of mechanisms for induction of brown adipose tissue recruitment but also for understanding the mechanism behind e.g. certain endocrine neoplasias. - Highlights: • cAMP can mimick norepinephrine-induced proliferation of brown preadipocytes. • The cAMP-induced proliferation can occur in the absence of serum, of any other growth factors, and of insulin. • Erk1/2, PI{sub 3}K and mTOR are cAMP activated but not involved in induction of proliferation. • A Protein Kinase C member may be in the signalling cascade. • This pathway analysis may also be of importance for certain endocrine hyper- and neoplasias.

  4. Protein kinase A-mediated cell proliferation in brown preadipocytes is independent of Erk1/2, PI3K and mTOR

    International Nuclear Information System (INIS)

    The physiological agonist norepinephrine promotes cell proliferation of brown preadipocytes during the process of tissue recruitment. In a primary culture system, cAMP mediates these adrenergic effects. In the present study, we demonstrated that, in contrast to other systems where the mitogenic effect of cAMP requires the synergistic action of (serum) growth factors, especially insulin/IGF, the cAMP effect in brown preadipocytes was independent of serum and insulin. Protein kinase A, rather than Epac, mediated the cAMP mitogenic effect. The Erk 1/2 family of MAPK, the PI3K system and the mTOR complexes were all activated by cAMP, but these activations were not necessary for cAMP-induced cell proliferation; a protein kinase C isoform may be involved in mediating cAMP-activated cell proliferation. We conclude that the generally acknowledged cellular mediators for induction of cell proliferation are not involved in this process in the brown preadipocyte system; this conclusion may be of relevance both for examination of mechanisms for induction of brown adipose tissue recruitment but also for understanding the mechanism behind e.g. certain endocrine neoplasias. - Highlights: • cAMP can mimick norepinephrine-induced proliferation of brown preadipocytes. • The cAMP-induced proliferation can occur in the absence of serum, of any other growth factors, and of insulin. • Erk1/2, PI3K and mTOR are cAMP activated but not involved in induction of proliferation. • A Protein Kinase C member may be in the signalling cascade. • This pathway analysis may also be of importance for certain endocrine hyper- and neoplasias

  5. Adipose Tissue Fatty Acid Storage Factors: Effects of Depot, Sex and Fat Cell Size

    OpenAIRE

    Hames, Kazanna C.; Koutsari, Christina; Santosa, Sylvia; Bush, Nikki C.; Jensen, Michael D.

    2015-01-01

    Background/Objectives Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetases (ACS; the first step in fat metabolism), and diacylglycerol acetyl-transferase (DGAT; the final step of triglyceride synthesis). Our goal was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots, and adipocyte size. Subje...

  6. Angiotensin II induces Fat1 expression/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation

    OpenAIRE

    Bruder-Nascimento, T; Chinnasamy, P; Riascos-Bernal, DF; Cau, SB; Callera, GE; Touyz, RM; Tostes, RC; Sibinga, NES

    2014-01-01

    Fat1 is an atypical cadherin that controls vascular smooth muscle cell (VSMC) proliferation and migration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) is an important source of reactive oxygen species (ROS) in VSMCs. Angiotensin II (Ang II) induces the expression and/or activation of both Fat1 and Nox1 proteins. This study tested the hypothesis that Ang II-induced Fat1 activation and VSMC migration are mediated by Nox1-dependent ROS generation and redox signaling. Stu...

  7. Research progress of autologous fat graft and fat cells apoptosis%自体脂肪移植与脂肪细胞凋亡的研究进展

    Institute of Scientific and Technical Information of China (English)

    朱晓飞

    2015-01-01

    自体脂肪移植由于填充效果佳、可塑性强、无排斥免疫反应、取材方便、创伤小等优点,而成为美容医学和整形外科常用的手术方法.但由于术后脂肪细胞成活率较低,从而限制了其在临床的广范应用.细胞凋亡是移植后脂肪细胞死亡的重要机制,通过抑制脂肪细胞的凋亡可明显提高自体脂肪移植的存活率,现将凋亡相关研究进展于自体脂肪移植中的应用进行综述.%Autologous fat graft has become the most commonly operation method in aestheticmedicine and plastic surgery,due to its better filling effect,strong plasticity, no immune response,easydrawing materials and little trauma.However,the low survival rate of fat cells,which limits its wideapplication in clinic. Apoptosis is an important mechanism of fat cell death which after transplantation.The survival rate of autologous fat transplantation can be significantly improved by inhibiting theapoptosis of fat cells,related factors affecting the survival rate of grafted fat was reviewed in this paper.

  8. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel;

    2011-01-01

    this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN...... not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect ß-cells......Fatty acid-induced damage in pancreatic ß-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve ß-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of...

  9. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel;

    2011-01-01

    this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN...... not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells......Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of...

  10. The Possible Potentiating Role of Endoplasmic Reticulum Stress Response Inhibitors in Trans-Differentiation of white to Brown Adipocytes

    Directory of Open Access Journals (Sweden)

    Ali Mohammad Sharifi

    2012-01-01

    Full Text Available The brown adipose tissue (BAT is an organ with the specialised function of intracellular fat oxidation; in other words, brown fat points to a potential natural tool by which energy expenditure is being stimulated. Obesity is a serious illness which can lead to many medical complications such as cardiovascular disorders. The BAT production, therefore, could be a promising therapeutic strategy for managing obesity. While different approaches have been examined to generate brown adipocytes from various precursor cells, no study has proposed an efficient procedure for direct trans-differentiation of white to brown adipocytes. Bone morphogenic protein (BMP-7 is a possible potential agent by which most of the main factors involved in induction of brown adipocytogenesis such as early regulators of brown fat fate, positive regulatory domain containing 16 (PRDM16 and peroxisome proliferator-activated receptor gamma (PPARγ coactivator-1 alpha (PGC-1α are stimulated, but the rate of success was not so promising. It has been documented that mature white adipocytes exert endoplasmic reticulum stress response (ESR and consequently unfolded protein response (UPR becomes activated for the purpose of ESR recovery since the ESR exceeds the capacity of UPR to overcome the imposed stress, and in turn disables the cell to manage the protein synthesis cascade including those required for BMP-7 induction of brown adipogenesis. This was performed using three main ESR sensors: PKR-like endoplasmic reticulum kinase (PERK, inositol requiring enzyme-1 (IRE-1 and activating transcription factor 6 alpha (ATF-6α resulting in attenuation of protein translation by blocking the activation of transcriptional machinery of UPR genes and the cell behaviour would also be changed towards apoptosis.It may suggest and propose the hypothesis that pretreatment of the white adipocyte with an ESR inhibitor such as salubrinal by reducing ESR and turning on the protein synthesis machinery

  11. The Difference in Prognosis between Renal Sinus Fat and Perinephric Fat Invasion for pT3a Renal Cell Carcinoma: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Zhiling Zhang

    Full Text Available In the current Tumour-Node-Metastasis (TNM classification system for renal cell carcinoma (RCC, both renal sinus fat invasion (SFI and perinephric fat invasion (PFI are defined as T3a, suggesting that the prognosis should be similar for the two pathologic findings. Several studies, however, have reported a worse prognosis for SFI in patients with a T3a tumor. In order to compare the prognosis of these two pathologic findings (SFI versus. PFI in a more comprehensive way, this meta-analysis was performed.To identify relevant studies, Medline, Embase, Cochrane Library, and Scopus database were searched from the inception until October 2014. A meta-analysis was performed using Review Manager 5.2 and STATA 11. Pooled Odds ratio (OR and/or hazard ratio (HR with 95% confidence interval (CI were calculated to examine the risk or hazard association.A total of 6 studies including 1031 patients qualified for analysis. T3a RCC patients with SFI were significantly associated with poor cancer specific survival(CSS (HR: 1.47, 95% CI: 1.19-1.83; P<0.001 compared to those with PFI. In T3aNx/N0M0 subgroup, SFI patients also showed a worse prognosis than those with PFI (CSS, HR: 1.94, 95% CI: 1.21-3.12; P = 0.006. T3a RCC patients with SFI had higher Furhman grade, greater possibility of lymph node metastasis, sarcomatoid differentiation and tumour necrosis. Main limitation is the relatively small number of included studies.The present meta-analysis suggested that SFI is associated with worse CSS in patients with pT3a RCC. However, due to the small number of included studies, future studies with a large sample size are required to further verify our findings.

  12. Fibroblast Growth Factor 21 Suppresses Adipogenesis in Pig Intramuscular Fat Cells

    Directory of Open Access Journals (Sweden)

    Yongliang Wang

    2015-12-01

    Full Text Available Fibroblast growth factor 21 (FGF21 plays an important role in the treatment of disease associated with muscle insulin resistance which is characterized by various factors, such as intramuscular triglyceride (IMT content. Studies have also shown that FGF21 inhibits triglyceride synthesis in vivo. However, the precise mechanism whereby FGF21 regulates triglyceride metabolism in intramuscular fat (IMF, which may influence the muscle insulin sensitivity, is not clearly understood. In order to understand the role of FGF21 in IMF deposition, we performed FGF21 overexpression in IMF cells by stable transfection. Our results showed that FGF21 inhibited the key adipogenesis gene mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG, CCAAT/enhancer-binding protein (CEBP family by reducing lysine-specific demethylase 1 (LSD1 expression which led to significant decline in lipid accumulation, and the result was confirmed by Western blot. Moreover, triggered by FGF21, parts of the adipokines—fatty acid-binding protein 4 (FABP4, glucose transporter 4 (GLUT4, adiponectin (ADIPOQ, and perilipin (PLIN1—were also down-regulated. Furthermore, FGF21 gene expression was suppressed by transcription factor CEBP beta (CEBPB which contributed strongly to triglyceride synthesis. Taken together, our study is the first to experimentally demonstrate FGF21 emerging as an efficient blockade of adipogenesis in IMF, thus also providing a new understanding of the mechanism whereby FGF21 improves insulin sensitivity.

  13. Intrinsic differences in adipocyte precursor cells from different white fat depots

    DEFF Research Database (Denmark)

    Macotela, Yazmín; Emanuelli, Brice; Mori, Marcelo A;

    2012-01-01

    Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. In the current study, we demonstrate...... is higher in obesity-prone C57BL/6 mice than obesity-resistant 129 mice, and the number in both depots is increased by up to 270% by exposure of mice to high-fat diet. Thus, APCs from visceral and subcutaneous depots are dynamic populations, which have intrinsic differences in gene expression...

  14. Role of macropore flow in the transport of Escherichia coli cells in undisturbed cores of a brown leached soil.

    Science.gov (United States)

    Martins, Jean M F; Majdalani, Samer; Vitorge, Elsa; Desaunay, Aurélien; Navel, Aline; Guiné, Véronique; Daïan, Jean François; Vince, Erwann; Denis, Hervé; Gaudet, Jean Paul

    2013-02-01

    The objective of this work was to evaluate the transport of Escherichia coli cells in undisturbed cores of a brown leached soil collected at La Côte St André (France). Two undisturbed soil cores subjected to repeated injections of bacterial cells and/or bromide tracer were used to investigate the effect of soil hydrodynamics and ionic strength on cell mobility. Under the tested experimental conditions, E. coli cells were shown to be transported at the water velocity (retardation factor close to 1) and their retention appeared almost insensitive to water flow and ionic strength variations, both factors being known to control bacterial transport in model saturated porous media. In contrast, E. coli breakthrough curves evolved significantly along with the repetition of the cell injections in each soil core, with a progressive acceleration of their transport. The evolution of E. coli cells BTCs was shown to be due to the evolution of the structure of soil hydraulic pathways caused by the repeated water infiltrations and drainage as may occur in the field. This evolution was demonstrated through mercury intrusion porosimetry (MIP) performed on soil aggregates before and after the repeated infiltrations of bacteria. MIP revealed a progressive and important reduction of the soil aggregate porosity, n, that decreased from approximately 0.5 to 0.3, along with a decrease of the soil percolating step from 27 to 2 μm. From this result a clear compaction of soil aggregates was evidenced that concerned preferentially the pores larger than 2 μm equivalent diameter, i.e. those allowing bacterial cell passage. Since no significant reduction of the global soil volume was observed at the core scale, this aggregate compaction was accompanied by macropore formation that became progressively the preferential hydraulic pathway in the soil cores, leading to transiently bi-modal bacterial BTCs. The evolution of the soil pore structure induced a modification of the main hydrodynamic

  15. Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1.

    Science.gov (United States)

    Zhang, Nannan; Li, Zhongchi; Xu, Kang; Wang, Yanying; Wang, Zhao

    2016-01-01

    Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction. PMID:27582325

  16. Effect of bacterial lectin on acceleration of fat cell lipolysis at in vitro diode laser treatment using encapsulated ICG

    Science.gov (United States)

    Yanina, Irina Yu.; Kochubey, Vyacheslav I.; Tuchin, Valery V.; Portnov, Sergey A.; Svenskaya, Yuliya I.; Gorin, Dmitry A.; Ponomareva, Elena G.; Nikitina, Valentina E.

    2012-03-01

    The influence of bacterial lectin on photochemically induced fat cell lipolysis was studied. Resulting capsules were tested for ICG absorption by optical spectra measurements. To separate released and encapsulated ICG supernatant was removed and capsules were redispered in pure deionized water. Supernatant and capsule suspension spectra were measured separately. It was also found that pretreatment of tissue by lectin leads to acceleration of lipolysis at photochemical treatment. The data obtained can be used to enhance efficiency of photochemical therapy.

  17. Human induced pluripotent stem cells: A new source for brown and white adipocytes

    Institute of Scientific and Technical Information of China (English)

    Anne-Laure; Hafner; Christian; Dani

    2014-01-01

    Mesenchymal stem cells(MSCs) derived from human induced pluripotent stem cells(hiPSCs) provide a novel source for generating adipocytes, thus opening new avenues for fundamental research and clinical medicine. We present the adipogenic potential of hiPSCs and the various methods to derive hiPSC-MSCs. We discuss the main characteristic of hiPSC-MSCs, which is their low adipogenic capacity as compared to adult-MSCs. Finally, we propose several hypotheses to explanation this feature, underlying a potential critical role of the micro-environment. We favour the hypothesis that the range of factors or culture conditions required to induce adipocyte differentiation of MSCs derived from adult tissues and from embryonic-like cells could differ.

  18. Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport.

    OpenAIRE

    Ibrahimi, A.; Sfeir, Z; Magharaie, H; Amri, E Z; Grimaldi, P.; Abumrad, N A

    1996-01-01

    An adipocyte membrane glycoprotein, (FAT), homologous to human CD36, has been previously implicated in the binding/transport of long-chain fatty acids. It bound reactive derivatives of long-chain fatty acids and binding was specific and associated with significant inhibition of fatty acid uptake. Tissue distribution of the protein and regulation of its expression were also consistent with its postulated role. In this report, we have examined the effects of FAT expression on rates and properti...

  19. Fat tissue, aging, and cellular senescence.

    OpenAIRE

    Tchkonia, T.; Morbeck, D.E.; Zglinicki, T. von; Deursen, J.M.A. van; Lustgarten, J.; Scrable, H.; Khosla, S.; Jensen, M.D.; Kirkland, J L

    2010-01-01

    Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dys...

  20. MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes.

    Science.gov (United States)

    Kim, Hye-Jin; Cho, Hyunjii; Alexander, Ryan; Patterson, Heide Christine; Gu, Minxia; Lo, Kinyui Alice; Xu, Dan; Goh, Vera J; Nguyen, Long N; Chai, Xiaoran; Huang, Cher X; Kovalik, Jean-Paul; Ghosh, Sujoy; Trajkovski, Mirko; Silver, David L; Lodish, Harvey; Sun, Lei

    2014-12-01

    Brown adipose tissue (BAT) is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs (miRNAs) as essential regulators of brown adipocyte differentiation, but whether miRNAs are required for the feature maintenance of mature brown adipocytes remains unknown. To address this question, we ablated Dgcr8, a key regulator of the miRNA biogenesis pathway, in mature brown as well as in white adipocytes. Adipose tissue-specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat and were intolerant to cold exposure. Primary brown adipocyte cultures in vitro confirmed that miRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that miRNAs are essential for the browning of subcutaneous white adipocytes in vitro and in vivo. Using this animal model, we performed miRNA expression profiling analysis and identified a set of BAT-specific miRNAs that are upregulated during brown adipocyte differentiation and enriched in brown fat compared with other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of miRNAs in the maintenance as well as in the differentiation of brown adipocytes.

  1. MicroRNAs Are Required for the Feature Maintenance and Differentiation of Brown Adipocytes

    Science.gov (United States)

    Kim, Hye-Jin; Cho, Hyunjii; Alexander, Ryan; Patterson, Heide Christine; Gu, Minxia; Lo, Kinyui Alice; Xu, Dan; Goh, Vera J.; Nguyen, Long N.; Chai, Xiaoran; Huang, Cher X.; Kovalik, Jean-Paul; Ghosh, Sujoy; Trajkovski, Mirko; Silver, David L.; Lodish, Harvey

    2014-01-01

    Brown adipose tissue (BAT) is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs (miRNAs) as essential regulators of brown adipocyte differentiation, but whether miRNAs are required for the feature maintenance of mature brown adipocytes remains unknown. To address this question, we ablated Dgcr8, a key regulator of the miRNA biogenesis pathway, in mature brown as well as in white adipocytes. Adipose tissue–specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat and were intolerant to cold exposure. Primary brown adipocyte cultures in vitro confirmed that miRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that miRNAs are essential for the browning of subcutaneous white adipocytes in vitro and in vivo. Using this animal model, we performed miRNA expression profiling analysis and identified a set of BAT-specific miRNAs that are upregulated during brown adipocyte differentiation and enriched in brown fat compared with other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of miRNAs in the maintenance as well as in the differentiation of brown adipocytes. PMID:25008181

  2. Inflammatory cytokines up-regulate FAT/CD36 expression in renal cells loaded by fatty acids%炎症对脂肪酸负荷的肾细胞FAT/CD36表达的影响

    Institute of Scientific and Technical Information of China (English)

    万克强; 廖俊蕾; 赵蕾; 李青; 陈压西; 阮雄中

    2012-01-01

    目的:观察炎症是否干扰脂肪酸负荷的肾细胞[人系膜细胞(HMCs)和肾小管上皮细胞HK-2]脂肪酸转运蛋白(FAT/CD36)的表达.方法:分别给予不同浓度软脂酸(0 mmol/L、0.02 mmol/L、0.04 mmol/L、0.08 mmol/L、0.16 mmol/L、0.32 mmol/L)处理HMCs和HK-2细胞24 h.采用实时定量PCR和Western blotting方法检测细胞FAT/CD36的mRNA及蛋白的表达.进一步选取0.04 mmol/L软脂酸联合炎症因子(25 μg/L TNF-α或20 μg/L IL-6)处理肾细胞24 h后,观察炎症因子对肾细胞FAT/CD36 mRNA及蛋白表达的影响;油红O染色及酶比色法检测细胞甘油三酯(TG)水平;ELISA检测细胞游离脂肪酸(FFA)含量.结果:软脂酸呈浓度依赖性上调HMCs和HK-2细胞FAT/CD36 mRNA和蛋白表达.炎症因子明显刺激脂肪酸负荷的肾细胞FAT/CD36 mRNA和蛋白表达进一步增加.油红O染色及胞内TG和FFA含量测定显示炎症因子促进肾细胞脂质积聚.结论:炎症上调脂肪酸负荷的肾细胞FAT/CD36表达,加重胞内脂质积聚.%AIM: To investigate the effects of inflammatory cytokines on the expression of fatty acid transporter ( FAT/CD36 ) in renal cells loaded by fatty acids. METHODS: Human mesangial cells ( HMCs ) and renal tubular epithelial HK -2 cells were treated with palmitate at concentrations of 0 mmol/L, 0. 02 mmol/L, 0. 04 mmol/L, 0. 08 mmol/L, 0. 16 mmol/L and 0. 32 mmol/L for 24 h. The expression of FAT/CD36 at mRNA and protein levels was detected by real - time PCR and Western blotting, respectively. The renal cells were treated with palmitate at concentration of 0. 04 mmol/L combined with TNF - a ( 25 μg/L ) or IL - 6 ( 20 μg/L ) for 24 h. The effect of inflammatory cytokines on the mRNA and protein levels of FAT/CD36 in the renal cells was also investigated. Oil red 0 staining was used to determine the intracellular lipid droplet formation. The intracellular triglyceride ( TG ) and free fatty acid ( FFA ) were measured by enzymic assay and ELISA, respectively

  3. Degradation Mechanism in a Direct Carbon Fuel Cell Operated with Demineralised Brown Coal

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Degradation mechanism studied for demineralised coal in a direct carbon fuel cell. • Diffusion limited processes dominate the electrode polarisation losses in pure N2. • Major fuel cell performance loss occurred due to loss of carbon/anode contacts. • The anode retained its phase structure with minor other phases formed in operation. - Abstract: The performance of a demineralised and devolatilised coal from the Morwell mine in the Latrobe Valley, Victoria, has been investigated in a direct carbon fuel cell (DCFC) operated at 850 °C. The focus of the investigation has been on understanding degradation issues as a function of time involving a sequence of electrochemical impedance spectroscopy and voltage-current characteristic. Diffusion limited processes dominate the electrode polarisation losses in pure N2 atmosphere, however, these decrease substantially in the presence of CO2 as the anode chamber purge gas, due to in situ generation of fuel species by the reaction of CO2 with carbon. Post-mortem analysis of anode by SEM and XRD revealed only a minor degradation due to its reduction, particle agglomeration as well as the formation of small quantity of new phases. However, major fuel cell performance degradation (increase of ohmic resistive and electrode polarisation losses) occurred due to loss of carbon/anode contacts and a reduction in the electron-conducting pathways as the fuel was consumed. The investigations revealed that the demineralised coal char can be used as a viable fuel for DCFC, however, further developments on anode materials and fuel feed mechanism would be required to achieve long-term sustained performance

  4. High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity

    Science.gov (United States)

    Park, Mi-Young; Kim, Min Young; Seo, Young Rok; Kim, Jong-Sang; Sung, Mi-Kyung

    2016-01-01

    Background: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in ApcMin/+ mice. Methods: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. Results: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2′-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis. PMID:27390738

  5. Heat stress enhances adipogenic differentiation of subcutaneous fat depot-derived porcine stromovascular cells.

    Science.gov (United States)

    Qu, H; Donkin, S S; Ajuwon, K M

    2015-08-01

    Heat stress (HS) results from excessive heat load on animals such that all adaptive mechanisms used to dissipate the heat do not return the body to normal body temperature. In pigs, HS results in increased fat deposition compared with pair-fed animals in a thermoneutral environment. Although there is evidence that HS increases activity of lipoprotein lipase (LPL) in adipose tissue of heat stressed pigs, the fundamental causes of the increased adiposity are still unknown. It remains unclear whether HS directly alters metabolism in adipocytes. Therefore, to understand the mechanism of HS effects on porcine adipocytes, we used an in vitro adipocyte differentiation model to characterize cellular responses that occur during differentiation of pig adipocytes. Preadipocytes (stromovascular cells) were differentiated for 9 d at a normal (37°C) or HS (41.5°C) temperature under 5% CO. Expressions of HS genes such as heat shock proteins (HSP; HSP27, HSP60, HSP70, and HSP90), adipogenic markers peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding proteins α (C/EBPα), fatty acid synthase (FAS), adipocyte protein 2 (aP2), fatty acid translocase 36 (CD36), fatty acid transport protein 4 (FATP4), fatty acid transport protein 6 (FATP6), LPL, glucose transporter protein type 4 (GLUT4), phosphoenolpyruvate carboxykinase 1 (PCK1 or PEPCK-C), and glycerol kinase (GK) and adipokines (adiponectin and leptin) were determined by real-time-PCR and immunoblotting or ELISA. Cellular triglyceride (TAG) and ATP concentrations were also determined. As expected, HS increased ( CD36, FATP4, FATP6, LPL, GLUT4, PCK1, and GK). This is supported by increased cellular TAG under HS. Therefore, HS promotes increased adipocyte TAG storage, perhaps through upregulation of genes involved in fatty acid uptake and TAG synthesis. PMID:26440163

  6. Transcriptional pathways in cPGI2-induced adipocyte progenitor activation for browning

    Directory of Open Access Journals (Sweden)

    Irem eBayindir

    2015-08-01

    Full Text Available De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2 as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying beta-adrenergic stimulation to the progenitor level. Here we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation towards an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation.

  7. Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

    Science.gov (United States)

    Nana, Yang; Peng, Jiao; Jianlin, Zhang; Xiangjian, Zhang; Shutong, Yao; Enxin, Zhan; Bin, Li; Chuanlong, Zong; Hua, Tian; Yanhong, Si; Yunsai, Du; Shucun, Qin; Hui, Wang

    2015-01-01

    Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

  8. Effects of Yamase climatic condition during the pollen mother cell developmental stage on concentrations of Cs and Sr in brown rice

    International Nuclear Information System (INIS)

    Effects of the Yamase climatic condition on the concentration of alkali metals and alkaline earth metals in brown rice were examined in relation to the soil-to-plant transfer factors of 137Cs and 90Sr. Rice plants (Oryza sativa L cv. Yumeakari) were cultivated in an artificial climate chamber, and exposed to a simulated Yamase condition for 3 or 7 d during the pollen mother cell developmental stage. In these simulated treatments, temperature and light intensity were set to 5degC lower and 50% lower than the respective control values. Fog was generated with visibility of 70±30 m. Concentrations of alkali metals, alkaline earth metals and the other minor elements in brown rice samples were analyzed. Measured Cs and Sr concentrations were found to be unaffected by the Yamase treatments, while concentrations of Fe, Cu, Zn and Mo were increased. (author)

  9. Ionizing Radiation Potentiates High Fat Diet-Induced Insulin Resistance and Reprograms Skeletal Muscle and Adipose Progenitor Cells

    DEFF Research Database (Denmark)

    Nylander, Vibe; Ingerslev, Lars R; Andersen, Emil;

    2016-01-01

    Exposure to ionizing radiation increases the risk of chronic metabolic disorders such as insulin resistance and type 2 diabetes later in life. We hypothesized that irradiation reprograms the epigenome of metabolic progenitor cells, which could account for impaired metabolism after cancer treatment....... C57Bl/6 mice were treated with a single dose of irradiation and subjected to high fat diet (HFD). RNA Sequencing and Reduced Representation Bisulfite Sequencing were used to create transcriptomic and epigenomic profiles of preadipocytes and skeletal muscle satellite cells collected from irradiated...

  10. Phenotypic and Functional Properties of Porcine Dedifferentiated Fat Cells during the Long-Term Culture In Vitro

    Directory of Open Access Journals (Sweden)

    Xuewu Peng

    2015-01-01

    Full Text Available It has been proved that terminally differentiated mature adipocytes possess abilities to dedifferentiate into fibroblast-like progeny cells with self-renewal and multiple differentiation, termed dedifferentiated fat (DFAT cells. However, the biological properties of DFAT cells during long-term culture in vitro have not been elucidated. Here, we obtained fibroblast-like morphology of porcine DFAT cells by ceiling culture. During the dedifferentiation process, round mature adipocytes with single large lipid droplets changed into spindle-shaped cells accompanied by the adipogenic markers PPARγ, aP2, LPL, and Adiponectin significant downregulation. Flow cytometric analysis showed that porcine DFAT cells displayed similar cell-surface antigen profile to mesenchymal stem cells (MSCs. Furthermore, different passages of porcine DFAT cells during long-term culture in vitro retained high levels of cell viabilities (>97%, efficient proliferative capacity including population doubling time ranged from 20 h to 22 h and population doubling reached 47.40±1.64 by 58 days of culture. In addition, porcine DFAT cells maintained the multiple differentiation capabilities into adipocytes, osteoblasts, and skeletal myocytes and displayed normal chromosomal karyotypes for prolonged passaging. Therefore, porcine DFAT cells may be a novel model of stem cells for studying the functions of gene in the different biological events.

  11. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to fats and “function of the cell membrane” (ID 622, 2900, 2911) and normal absorption of fat-soluble vitamins (ID 670, 2902) pursuant to Article 13(1) of Regulation (EC

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to fats and “function of the cell membrane” and normal absorption of fat-soluble vitamins. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member...... States or directly from stakeholders. The food constituent that is the subject of the health claims is fats. The Panel considers that fats are sufficiently characterised in relation to the claimed effects....

  12. Contrasting effects of cold acclimation versus obesogenic diets on chemerin gene expression in brown and brite adipose tissues.

    Science.gov (United States)

    Hansen, Ida R; Jansson, Kim M; Cannon, Barbara; Nedergaard, Jan

    2014-12-01

    Based on results from a signal sequence trap, we investigated chemerin gene expression in brown adipose tissue. Male NMRI mice were exposed to 30, 22 or 4 °C for 3 weeks, or were fed control (chow) diet, cafeteria diet or high-fat diet at thermoneutrality for the same time. In brown adipose tissue, cold acclimation strongly diminished chemerin gene expression, whereas obesogenic diets augmented expression. Qualitatively, changes in expression were paralleled in brite/beige adipose tissues (e.g. inguinal), whereas white adipose tissue (epididymal) and muscle did not react to these cues. Changes in tissue expression were not directly paralleled by alterations in plasma levels. Both these intact animal studies and brown adipocyte cell culture studies indicated that the gene expression regulation was not congruent with a sympathetic/adrenergic control. The data are discussed in relation to suggested endocrine, paracrine and autocrine effects of chemerin.

  13. Vitamin B12, a chlorophyll-related analog to pheophytin a from marine brown algae, promotes neurite outgrowth and stimulates differentiation in PC12 cells

    OpenAIRE

    Ina, Atsutoshi; Kamei, Yuto

    2006-01-01

    We previously isolated an analog to chlorophyll-related compounds, pheophytin a, from the marine brown alga Sargassum fulvellum and demonstrated that it is a neurodifferentiation compound. In the current study, we investigated the effects of the pheophytin a analog vitamin B12 on PC12 cell differentiation. In the presence of a low level of nerve growth factor (10 ng ml−1), vitamin B12 demonstrated neurite outgrowth-promoting activity in PC12 cells. The effect was dose-dependent in the range o...

  14. Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues.

    Science.gov (United States)

    Ramseyer, Vanesa D; Granneman, James G

    2016-01-01

    The discovery of brown adipose tissue in adult humans along with the recognition of adipocyte heterogeneity and plasticity of white fat depots has renewed the interest in targeting adipose tissue for therapeutic benefit. Adrenergic activation is a well-established means of recruiting catabolic adipocyte phenotypes in brown and white adipose tissues. In this article, we review mechanisms of brown adipocyte recruitment by the sympathetic nervous system and by direct β-adrenergic receptor activation. We highlight the distinct modes of brown adipocyte recruitment in brown, beige/brite, and white adipose tissues, UCP1-independent thermogenesis, and potential non-thermogenic, metabolically beneficial effects of brown adipocytes.

  15. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad.

    Science.gov (United States)

    Nickerson, Nicole K; Mohammad, Khalid S; Gilmore, Jennifer L; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A; Foley, John

    2012-01-01

    Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01), reduced osteolytic lesion tumor volume (p<0.01), increased survivorship in vivo (p<0.001), and resulted in decreased MDA-231 growth in the fat pad (p<0.01). Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1) and matrix metalloproteinase 9 (MMP9), both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland. PMID:22276166

  16. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad.

    Directory of Open Access Journals (Sweden)

    Nicole K Nickerson

    Full Text Available Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231, and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01, reduced osteolytic lesion tumor volume (p<0.01, increased survivorship in vivo (p<0.001, and resulted in decreased MDA-231 growth in the fat pad (p<0.01. Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1 and matrix metalloproteinase 9 (MMP9, both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland.

  17. Coconut fats.

    Science.gov (United States)

    Amarasiri, W A L D; Dissanayake, A S

    2006-06-01

    In many areas of Sri Lanka the coconut tree and its products have for centuries been an integral part of life, and it has come to be called the "Tree of life". However, in the last few decades, the relationship between coconut fats and health has been the subject of much debate and misinformation. Coconut fats account for 80% of the fat intake among Sri Lankans. Around 92% of these fats are saturated fats. This has lead to the belief that coconut fats are 'bad for health', particularly in relation to ischaemic heart disease. Yet most of the saturated fats in coconut are medium chain fatty acids whose properties and metabolism are different to those of animal origin. Medium chain fatty acids do not undergo degradation and re-esterification processes and are directly used in the body to produce energy. They are not as 'bad for health' as saturated fats. There is the need to clarify issues relating to intake of coconut fats and health, more particularly for populations that still depend on coconut fats for much of their fat intake. This paper describes the metabolism of coconut fats and its potential benefits, and attempts to highlight its benefits to remove certain misconceptions regarding its use.

  18. Processing and phosphorylation of the Fat receptor

    OpenAIRE

    Feng, Yongqiang; Irvine, Kenneth D.

    2009-01-01

    The Drosophila tumor suppressors fat and discs overgrown (dco) function within an intercellular signaling pathway that controls growth and polarity. fat encodes a transmembrane receptor, but post-translational regulation of Fat has not been described. We show here that Fat is subject to a constitutive proteolytic processing, such that most or all cell surface Fat comprises a heterodimer of stably associated N- and C-terminal fragments. The cytoplasmic domain of Fat is phosphorylated, and this...

  19. Signal transduction by the Fat cytoplasmic domain

    OpenAIRE

    Pan, Guohui; Feng, Yongqiang; Ambegaonkar, Abhijit A.; Sun, Gongping; Huff, Matthew; Rauskolb, Cordelia; Irvine, Kenneth D.

    2013-01-01

    The large atypical cadherin Fat is a receptor for both Hippo and planar cell polarity (PCP) pathways. Here we investigate the molecular basis for signal transduction downstream of Fat by creating targeted alterations within a genomic construct that contains the entire fat locus, and by monitoring and manipulating the membrane localization of the Fat pathway component Dachs. We establish that the human Fat homolog FAT4 lacks the ability to transduce Hippo signaling in Drosophila, but can trans...

  20. Brown adipose tissue growth and development.

    Science.gov (United States)

    Symonds, Michael E

    2013-01-01

    Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

  1. Planar cell polarity: the Dachsous/Fat system contributes differently to the embryonic and larval stages of Drosophila

    Directory of Open Access Journals (Sweden)

    Pedro Saavedra

    2016-04-01

    Full Text Available The epidermal patterns of all three larval instars (L1–L3 of Drosophila are made by one unchanging set of cells. The seven rows of cuticular denticles of all larval stages are consistently planar polarised, some pointing forwards, others backwards. In L1 all the predenticles originate at the back of the cells but, in L2 and L3, they form at the front or the back of the cell depending on the polarity of the forthcoming denticles. We find that, to polarise all rows, the Dachsous/Fat system is differentially utilised; in L1 it is active in the placement of the actin-based predenticles but is not crucial for the final orientation of the cuticular denticles, in L2 and L3 it is needed for placement and polarity. We find Four-jointed to be strongly expressed in the tendon cells and show how this might explain the orientation of all seven rows. Unexpectedly, we find that L3 that lack Dachsous differ from larvae lacking Fat and we present evidence that this is due to differently mislocalised Dachs. We make some progress in understanding how Dachs contributes to phenotypes of wildtype and mutant larvae and adults.

  2. Transgenesis of humanized fat1 promotes n-3 polyunsaturated fatty acid synthesis and expression of genes involved in lipid metabolism in goat cells.

    Science.gov (United States)

    Fan, Yixuan; Ren, Caifang; Wang, Zhibo; Jia, Ruoxin; Wang, Dan; Zhang, Yanli; Zhang, Guomin; Wan, Yongjie; Huang, Mingrui; Wang, Feng

    2016-01-15

    The n-3 fatty acid desaturase gene fat1 codes for the n-3 desaturase enzyme, which can convert n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. The n-3 PUFAs are essential components required for normal cellular function and have preventive and therapeutic effects on many diseases. Goat is an important domestic animal for human consumption of meat and milk. To elevate the concentrations of n-3 PUFAs and examine the regulatory mechanism of fat1 in PUFA metabolism in goat cells, we successfully constructed a humanized fat1 expression vector and confirmed the efficient expression of fat1 in goat ear skin-derived fibroblast cells (GEFCs) by qRT-PCR and Western blot analysis. Fatty acid analysis showed that fat1 overexpression significantly increased the levels of total n-3 PUFAs and decreased the levels of total n-6 PUFAs in GEFCs. In addition, qRT-PCR results indicate that the FADS1 and FADS2 desaturase genes, ELOV2 and ELOV5 elongase genes, ACO and CPT1 oxidation genes, and PPARa and PPARγ transcription factors are up-regulated, and transcription factors of SREBP-1c gene are down-regulated in the fat1 transgenic goat cells. Overall, fat1-overexpression resulted in an increase in the n-3 fatty acids and altered expression of PUFA synthesis related genes in GEFCs. This work lays a foundation for both the production of fat1 transgenic goats and further study of the mechanism of fat1 function in the PUFAs metabolism.

  3. Transgenesis of humanized fat1 promotes n-3 polyunsaturated fatty acid synthesis and expression of genes involved in lipid metabolism in goat cells.

    Science.gov (United States)

    Fan, Yixuan; Ren, Caifang; Wang, Zhibo; Jia, Ruoxin; Wang, Dan; Zhang, Yanli; Zhang, Guomin; Wan, Yongjie; Huang, Mingrui; Wang, Feng

    2016-01-15

    The n-3 fatty acid desaturase gene fat1 codes for the n-3 desaturase enzyme, which can convert n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. The n-3 PUFAs are essential components required for normal cellular function and have preventive and therapeutic effects on many diseases. Goat is an important domestic animal for human consumption of meat and milk. To elevate the concentrations of n-3 PUFAs and examine the regulatory mechanism of fat1 in PUFA metabolism in goat cells, we successfully constructed a humanized fat1 expression vector and confirmed the efficient expression of fat1 in goat ear skin-derived fibroblast cells (GEFCs) by qRT-PCR and Western blot analysis. Fatty acid analysis showed that fat1 overexpression significantly increased the levels of total n-3 PUFAs and decreased the levels of total n-6 PUFAs in GEFCs. In addition, qRT-PCR results indicate that the FADS1 and FADS2 desaturase genes, ELOV2 and ELOV5 elongase genes, ACO and CPT1 oxidation genes, and PPARa and PPARγ transcription factors are up-regulated, and transcription factors of SREBP-1c gene are down-regulated in the fat1 transgenic goat cells. Overall, fat1-overexpression resulted in an increase in the n-3 fatty acids and altered expression of PUFA synthesis related genes in GEFCs. This work lays a foundation for both the production of fat1 transgenic goats and further study of the mechanism of fat1 function in the PUFAs metabolism. PMID:26474750

  4. Activation of Kupffer Cells Is Associated with a Specific Dysbiosis Induced by Fructose or High Fat Diet in Mice.

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    Gladys Ferrere

    Full Text Available The increase consumption of fructose in diet is associated with liver inflammation. As a specific fructan substrate, fructose may modify the gut microbiota which is involved in obesity-induced liver disease. Here, we aimed to assess whether fructose-induced liver damage was associated with a specific dysbiosis, especially in mice fed a high fat diet (HFD. To this end, four groups of mice were fed with normal and HFD added or not with fructose. Body weight and glucose sensitivity, liver inflammation, dysbiosis and the phenotype of Kupffer cells were determined after 16 weeks of diet. Food intake was increased in the two groups of mice fed with the HFD. Mice fed with HFD and fructose showed a higher infiltration of lymphocytes into the liver and a lower inflammatory profile of Kupffer cells than mice fed with the HFD without fructose. The dysbiosis associated with diets showed that fructose specifically prevented the decrease of Mouse intestinal bacteria in HFD fed mice and increased Erysipelotrichi in mice fed with fructose, independently of the amount of fat. In conclusion, fructose, used as a sweetener, induced a dysbiosis which is different in presence of fat in the diet. Consequently, the activation of Kupffer cells involved in mice model of HFD-induced liver inflammation was not observed in an HFD/fructose combined diet. These data highlight that the complexity of diet composition could highly impact the development of liver lesions during obesity. Specific dysbiosis associated with the diet could explain that the progressions of liver damage are different.

  5. Genes expressed in the Drosophila head reveal a role for fat cells in sex-specific physiology

    OpenAIRE

    Fujii, Shinsuke; Amrein, Hubert

    2002-01-01

    The downstream effectors of the Drosophila sex determination cascade are mostly unknown and thought to mediate all aspects of sexual differentiation, physiology and behavior. Here, we employed serial analysis of gene expression (SAGE) to identify male and female effectors expressed in the head, and report 46 sex-biased genes (>4-fold/P < 0.01). We characterized four novel, male- or female-specific genes and found that all are expressed mainly in the fat cells in the head. Tsx (turn on sex-spe...

  6. Effect of Brown Rice Protein and Its Hydrolysates on Lipid Metabolism in High-fat Diet on Syrian hamsters%糙米蛋白及其酶解产物对喂食高脂饲料叙利亚金仓鼠脂质代谢的影响

    Institute of Scientific and Technical Information of China (English)

    张慧娟; Wally Yokoyama; 张晖

    2012-01-01

    This study investigated the effect of brown rice protein(BRP) and BRP hydrolysates(BRPH)on lipoprotein metabolism in Syrian Golden hamsters fed high-fat diets compared to casein.The supplements of brown rice protein and its hydrolysates reduced hepatic total lipid,total cholesterol and free cholesterol content of hamster.Meanwhile,the BRP and BRPH diet increased the fecal total lipid,total cholesterol and free cholesterol content.Moreover,BRPH significantly reduced the hamster body weight compared to control.%以动物性蛋白酪蛋白为对照,研究了糙米蛋白及其酶解产物对叙利亚金仓鼠脂质代谢的影响。糙米蛋白及其酶解产物降低了仓鼠肝脏中总脂肪、总胆固醇和游离胆固醇含量,同时增加了粪便中脂肪及胆固醇的排出量。糙米蛋白酶解产物还可以显著降低仓鼠的体重。

  7. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes

    Science.gov (United States)

    Calderon-Dominguez, María; Sebastián, David; Fucho, Raquel; Weber, Minéia; Mir, Joan F.; García-Casarrubios, Ester; Obregón, María Jesús; Zorzano, Antonio; Valverde, Ángela M.; Serra, Dolors

    2016-01-01

    The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders. PMID:27438137

  8. BROWN TUMOR OF THE FACIAL BONES

    Directory of Open Access Journals (Sweden)

    Violeta Trandafir

    2010-11-01

    Full Text Available Brown tumor arises as a direct result of the effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. The lesion localizes in areas of intense bone resorbtion, and the bone defect becomes filled with fibroblastic tissue that can deform the bone and simulate a neoplastic process. Brown tumors can affect the mandible, maxilla, clavicle, ribs and pelvic bones. Most patients with hyperparathyroidism are asymptomatic. Skeletal changes may represent the first manifestations of the disease. Radiologically, brown tumor in the jaws presents as a well-defined radiolucent osteolytic lesion, making it hard to differentiate it from other maxillary expansive lesions that can present with a similar imaging. Brown tumors exhibit no pathognomonic histologic changes. Differentiating between a brown tumor and other giant-cell tumors may be very difficult, even with histology. A final diagnosis can be defined only by evaluating the radiological findings with histopathological, laboratory and clinical data. At present, brown tumor is considered as a reparative cellular process rather than a real neoplasia. This phenomenon is considered as pathognomonic of hyperparathyroidism secondary to renal failure, especially in patients on long-term hemodialysis. The initial treatment of brown tumor involves control of hyperparathyroidism, regardless of whether it is primary or secondary. The clinical management of brown tumor aims primarily to reduce the elevated parathyroid hormone levels by pharmacological treatment. Surgical treatment is reserved to nonresponders or to patients with painful symptomatology or alteration of normal function. Brown tumor can recur if hyperparathyroidism persists or recurs.

  9. Association between FAT1 mutation and overall survival in patients with human papillomavirus–negative head and neck squamous cell carcinoma

    Science.gov (United States)

    Kim, Ki Tae; Kim, Bo‐Sung

    2016-01-01

    Abstract Background The purpose of this study was to characterize the mutation profile of FAT atypical cadherin 1 (FAT1) and determine the prognostic significance of FAT1 mutation for overall survival in patients with human papillomavirus (HPV)‐negative head and neck squamous cell carcinoma (HNSCC). Methods Data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) data portals and used as discovery and validation sets. FAT1 mutational status was determined in 234 and 37 patients with HPV‐negative HNSCC, respectively, and overall survival analysis was performed. For comparison, HPV‐positive patients were also analyzed for overall survival. Results Most of the identified nonsynonymous somatic FAT1 mutations were loss‐of‐function mutations. FAT1 mutation was significantly associated with better overall survival in HPV‐negative patients from both the TCGA cohort (p = .026) and the ICGC cohort (p = .047), but not in HPV‐positive patients. Conclusion FAT1 mutational status is a strong independent prognostic factor in patients with HPV‐negative HNSCC. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E2021–E2029, 2016 PMID:26876381

  10. Autologous Bone-Marrow-Derived-Mononuclear-Cells-Enriched Fat Transplantation in Breast Augmentation: Evaluation of Clinical Outcomes and Aesthetic Results in a 30-Year-Old Female

    Directory of Open Access Journals (Sweden)

    Dmitry Bulgin

    2013-01-01

    Full Text Available Autologous fat transfer (lipofilling is becoming an invaluable tool for breast augmentation as well as for breast reconstruction. Autologous lipofilling has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main limitation is unpredictable fat graft resorption, which ranges from 25% to 80%, probably as a result of ischaemia and lack of neoangiogenesis. To obviate these disadvantages, several studies have searched for new ways of increasing the viability of the transplanted fat tissue. One promising approach is to enrich the fat graft with autologous bone-marrow-derived mononuclear cells (BMMNCs before transplantation. BMMNCs produce many angiogenic and antiapoptotic growth factors, and their secretion is significantly enhanced by hypoxia. All of these mechanisms of actions could be beneficial for the stimulation of angiogenesis in ischemic tissues by BMMNCs administration. In our aesthetic surgery practice, we use fat transplantation enriched with BMMNCs, which caused a significant improvement in survival of fat grafts, compared with that of traditional lipofilling. Our experience with freshly isolated autologous fat enriched with BMMNCs for breast augmentation procedures is presented. The concept of this surgical and tissue handling technique is based on ability of BMMNCs to stimulate blood vessel growth.

  11. Aspectos produtivos da raça Pardo-Suíça no Brasil: Fatores de ajustamento, produção de leite e de gordura, e parâmetros genéticos Productive aspects of the brown Swiss Breed in Brazil: Adjustment factors, milk and fat yields, and genetic parameters

    Directory of Open Access Journals (Sweden)

    Francisco Palma Rennó

    2002-09-01

    Full Text Available Foi realizado um estudo sobre o desempenho produtivo da raça Pardo-Suíça com o objetivo de estimar fatores de ajustamento, avaliar fatores de ambiente e genéticos que influenciam a produção de leite, de gordura e a porcentagem de gordura, e estimar parâmetros genéticos para estas características produtivas. Foram avaliadas 11189 lactações de 5382 vacas Pardo-Suíças, de 1980 a 1999, oriundas de 201 rebanhos, sendo os registros de produção do serviço de controle leiteiro realizado pela Associação Brasileira de Criadores de Gado Pardo-Suíço. As lactações foram ajustadas por meio de fatores multiplicativos de ajustamento para duas ordenhas, períodos de lactação de 305 dias e produção a idade adulta. As médias estimadas, os respectivos desvios-padrão e os coeficientes de variação da produção de leite, produção de gordura e percentagem de gordura foram 5791,50 ± 1211,58 kg e 20,92%; 217,25 ± 47,36 kg e 21,80% e 3,78 ± 0,34 e 9,16%, respectivamente. Os efeitos de ano e época de partos, interação ano-época de partos, rebanho e grupo genético influenciaram as características estudadas, com exceção da época de partos sobre a percentagem de gordura. Os coeficientes de herdabilidade e repetibilidade estimados para a produção de leite e gordura foram 0,37e 0,40, e 0,36 e 0,37, respectivamente. A correlação genética entre a produção de leite e de gordura encontrada neste estudo foi de 0,96. Os resultados obtidos revelam a necessidade do ajustamento das produções de leite e gordura para os efeitos avaliados. As médias de produção de leite, de gordura e à percentagem de gordura apresentada demonstram o elevado desempenho produtivo da raça Pardo-Suíça nos rebanhos brasileiros.A study was carried on performance of the Brown Swiss cattle with the objective of estimating adjustment factors, evaluate some environment and genetics factors that affect milk and fat yields and fat percentage, and estimate

  12. Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet

    Science.gov (United States)

    Fiori, Jennifer L.; Shin, Yu-Kyong; Kim, Wook; Krzysik-Walker, Susan M.; González-Mariscal, Isabel; Carlson, Olga D.; Sanghvi, Mitesh; Moaddel, Ruin; Farhang, Kathleen; Gadkaree, Shekhar K.; Doyle, Maire E.; Pearson, Kevin J.; Mattison, Julie A.; de Cabo, Rafael; Egan, Josephine M.

    2013-01-01

    Eating a “Westernized” diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6–1, NKX2–2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes. PMID:23884882

  13. Ras signalling regulates differentiation and UCP1 expression in models of brown adipogenesis

    DEFF Research Database (Denmark)

    Murholm, Maria; Dixen, Karen; Hansen, Jacob B

    2010-01-01

    BACKGROUND: The Ras/Raf/MEK/ERK pathway has been recognised as an important signalling module in adipogenesis and adipocyte function, but whether it promotes or inhibits the formation of fat cells has not been reconciled. METHODS: Here we investigate the significance of Ras signalling intensity...... on two unrelated models of mouse brown adipocyte differentiation. RESULTS: A constitutively active H-Ras mutant (Ras V12) caused a complete block of adipose conversion, as manifested by a lack of both lipid accumulation and induction of adipocyte gene expression. The Ras V12-mediated impediment...

  14. Facts about polyunsaturated fats

    Science.gov (United States)

    ... and monounsaturated) fat in place of saturated and trans fats can benefit your health. Polyunsaturated fat is different than saturated fat and trans fat. These unhealthy fats can increase your risk for ...

  15. Phosphorylation at tyrosine 114 of Proliferating Cell Nuclear Antigen (PCNA) is required for adipogenesis in response to high fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Yuan-Hung; Ho, Po-Chun; Chen, Min-Shan; Hugo, Eric; Ben-Jonathan, Nira [Department of Cancer Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States); Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Laboratory, Cincinnati, OH 45267-0056 (United States); Wang, Shao-Chun, E-mail: shao-chun.wang@uc.edu [Department of Cancer Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States); Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Laboratory, Cincinnati, OH 45267-0056 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Proliferating Cell Nuclear Antigen (PCNA) is phosphorylated at Y114. Black-Right-Pointing-Pointer Phospho-Y114 of PCNA is not required for cell proliferation for normal growth. Black-Right-Pointing-Pointer MCE during adipogenesis is abolished in the lack of the phosphorylation. Black-Right-Pointing-Pointer Homozygous Y114F mice are resistant to high fat diet induced obesity. Black-Right-Pointing-Pointer Our results shed light on the interface between proliferation and differentiation. -- Abstract: Clonal proliferation is an obligatory component of adipogenesis. Although several cell cycle regulators are known to participate in the transition between pre-adipocyte proliferation and terminal adipocyte differentiation, how the core DNA synthesis machinery is coordinately regulated in adipogenesis remains elusive. PCNA (Proliferating Cell Nuclear Antigen) is an indispensable component for DNA synthesis during proliferation. Here we show that PCNA is subject to phosphorylation at the highly conserved tyrosine residue 114 (Y114). Replacing the Y114 residue with phenylalanine (Y114F), which is structurally similar to tyrosine but cannot be phosphorylated, does not affect normal animal development. However, when challenged with high fat diet, mice carrying homozygous Y114F alleles (PCNA{sup F/F}) are resistant to adipose tissue enlargement in comparison to wild-type (WT) mice. Mouse embryonic fibroblasts (MEFs) harboring WT or Y114F mutant PCNA proliferate at similar rates. However, when subjected to adipogenesis induction in culture, PCNA{sup F/F} MEFs are not able to re-enter the cell cycle and fail to form mature adipocytes, while WT MEFs undergo mitotic clonal expansion in response to the adipogenic stimulation, accompanied by enhanced Y114 phosphorylation of PCNA, and differentiate to mature adipocytes. Consistent with the function of Y114 phosphorylation in clonal proliferation in adipogenesis, fat tissues isolated from WT

  16. Inhibition of mouse brown adipocyte differentiation by second-generation antipsychotics.

    Science.gov (United States)

    Oh, Jee-Eun; Cho, Yoon Mi; Kwak, Su-Nam; Kim, Jae-Hyun; Lee, Kyung Won; Jung, Hyosan; Jeong, Seong-Whan; Kwon, Oh-Joo

    2012-09-30

    Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 μM) and partially by quetiapine (30 μM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPβ, PPARγ2, UCP-1, PGC-1α, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARγ 2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 μM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.

  17. Effects of sulfated fucan, ascophyllan, from the brown Alga Ascophyllum nodosum on various cell lines: a comparative study on ascophyllan and fucoidan.

    Science.gov (United States)

    Jiang, Zedong; Okimura, Takasi; Yokose, Takeshi; Yamasaki, Yasuhiro; Yamaguchi, Kenichi; Oda, Tatsuya

    2010-07-01

    The effects of fucose-containing sulfated polysaccharides, ascophyllan and fucoidan, isolated from the brown alga Ascophyllum nodosum, on the growth of various cell lines (MDCK, Vero, PtK(1), CHO, HeLa, and XC) were investigated. In a colony formation assay, ascophyllan and fucoidan showed potent cytotoxic effects on Vero and XC cells, while other cell lines were relatively resistant to these polysaccharides. Almost no significant effects of these polysaccharides were observed in the cell lines tested using the Alamar blue cytotoxicity assay over 48 h with varying initial cell densities (2500-20,000 cells/well) in growth medium. Interestingly, a significant growth promoting effect of ascophyllan on MDCK cells was observed, whereas treatment with fucoidan showed growth suppressive effects on this cell line under the same experimental conditions. These results suggest that ascophyllan is distinguishable from fucoidan in terms of their bioactivities. This is the first report of the growth promoting effects of a sulfated fucan on a mammalian cell line under normal growth conditions. PMID:20541128

  18. A fucan from the brown seaweed Spatoglossum schröederi inhibits Chinese hamster ovary cell adhesion to several extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    Rocha H.A.O.

    2001-01-01

    Full Text Available Fucans, a family of sulfated polysaccharides present in brown seaweed, have several biological activities. Their use as drugs would offer the advantage of no potential risk of contamination with viruses or particles such as prions. A fucan prepared from Spatoglossum schröederi was tested as a possible inhibitor of cell-matrix interactions using wild-type Chinese hamster ovary cells (CHO-K1 and the mutant type deficient in xylosyltransferase (CHO-745. The effect of this polymer on adhesion properties with specific extracellular matrix components was studied using several matrix proteins as substrates for cell attachment. Treatment with the polymer inhibited the adhesion of fibronectin to both CHO-K1 (2 x 10(5(and CHO-745 (2 x 10(5 and 5 x 10(5 cells. No effect was detected with laminin, using the two cell types. On the other hand, adhesion to vitronectin was inhibited in CHO-K1 cells and adhesion to type I collagen was inhibited in CHO-745 cells. In spite of this inhibition, the fucan did not affect either cell proliferation or cell cycle. These results demonstrate that this polymer is a new anti-adhesive compound with potential pharmacological applications.

  19. Analyses of genetic relationships between linear type traits, fat-to-protein ratio, milk production traits, and somatic cell count in first-parity Czech Holstein cows

    DEFF Research Database (Denmark)

    Zink, V; Zavadilová, L; Lassen, Jan;

    2014-01-01

    Genetic and phenotypic correlations between production traits, selected linear type traits, and somatic cell score were estimated. The results could be useful for breeding programs involving Czech Holstein dairy cows or other populations. A series of bivariate analyses was applied whereby (co......)variance components were estimated using average information (AI-REML) implemented via the DMU statistical package. Chosen phenotypic data included average somatic cell score per a 305-day standard first lactation as well as the production traits milk yield, fat yield, protein yield, fat percentage, and protein...... and protein yield. In total, 27 098 somatic cell score records were available. The strongest positive genetic correlation between production traits and linear type traits was estimated between udder width and fat yield (0.51 ± 0.04), while the strongest negative correlation estimated was between body...

  20. High fat diet increases melanoma cell growth in the bone marrow by inducing osteopontin and interleukin 6

    Science.gov (United States)

    Chen, Guang-Liang; Luo, Yubin; Eriksson, Daniel; Meng, Xianyi; Qian, Cheng; Bäuerle, Tobias; Chen, Xiao-Xiang; Schett, Georg; Bozec, Aline

    2016-01-01

    The impact of metabolic stress induced by obesity on the bone marrow melanoma niche is largely unknown. Here we employed diet induced obese mice model, where mice received high-fat (HFD) or normal diet (ND) for 6 weeks before challenge with B16F10 melanoma cells. Tumor size, bone loss and osteoclasts numbers were assessed histologically in the tibial bones. For defining the molecular pathway, osteopontin knock-out mice, interleukin 6 neutralizing antibody or Janus kinase 2 inhibition were carried out in the same model. Mechanistic studies such as adipocyte-melanoma co-cultures for defining adipocyte induced changes of tumor cell proliferation and expression profiles were also performed. As results, HFD enhanced melanoma burden in bone by increasing tumor area and osteoclast numbers. This process was associated with higher numbers of bone marrow adipocytes expressing IL-6 in direct vicinity to tumor cells. Inhibition of IL-6 or of downstream JAK2 blocked HFD-induced tumor progression. Furthermore, the phenotypic changes of melanoma cells triggered macrophage and osteoclast accumulation accompanied by increased osteopontin expression. Osteopontin triggered osteoclastogenesis and also exerted a positive feedback loop to tumor cells, which was abrogated in its absence. Metabolic stress by HFD promotes melanoma growth in the bone marrow by an increase in bone marrow adipocytes and IL-6-JAK2-osteopontin mediated activation of tumor cells and osteoclast differentiation. PMID:27049717

  1. Mice lacking natural killer T cells are more susceptible to metabolic alterations following high fat diet feeding.

    Directory of Open Access Journals (Sweden)

    Brittany V Martin-Murphy

    Full Text Available Current estimates suggest that over one-third of the adult population has metabolic syndrome and three-fourths of the obese population has non-alcoholic fatty liver disease (NAFLD. Inflammation in metabolic tissues has emerged as a universal feature of obesity and its co-morbidities, including NAFLD. Natural Killer T (NKT cells are a subset of innate immune cells that abundantly reside within the liver and are readily activated by lipid antigens. There is general consensus that NKT cells are pivotal regulators of inflammation; however, disagreement exists as to whether NKT cells exert pathogenic or suppressive functions in obesity. Here we demonstrate that CD1d(-/- mice, which lack NKT cells, were more susceptible to weight gain and fatty liver following high fat diet (HFD feeding. Compared with their WT counterparts, CD1d(-/- mice displayed increased adiposity and greater induction of inflammatory genes in the liver suggestive of the precursors of NAFLD. Calorimetry studies revealed a significant increase in food intake and trends toward decreased metabolic rate and activity in CD1d(-/- mice compared with WT mice. Based on these findings, our results suggest that NKT cells play a regulatory role that helps to prevent diet-induced obesity and metabolic dysfunction and may play an important role in mechanisms governing cross-talk between metabolism and the immune system to regulate energy balance and liver health.

  2. Control of brown adipose tissue glucose and lipid metabolism by PPARγ

    Directory of Open Access Journals (Sweden)

    William T. Festuccia

    2011-12-01

    Full Text Available Brown adipose tissue (BAT non-shivering thermogenesis impacts energy homeostasis in rodents and humans. Mitochondrial UCP1 in brown fat cells produce heat by dissipating the energy generated by the oxidation of fatty acids and glucose. In addition to thermogenesis and despite its small relative size, sympathetically activated BAT constitutes an important glucose, fatty acid and triacylglycerol-clearing organ, and such function could potentially be used to alleviate dyslipidemias, hyperglycemia and insulin resistance. To date, chronic sympathetic innervation and PPARγ activation are the only recognized inducers of BAT recruitment. Here, we review the major differences between these two inducers of BAT recruitment in the regulation of lipolysis, fatty acid oxidation, lipid uptake and triacylglycerol synthesis, glucose uptake and de novo lipogenesis. Whereas BAT recruitment through sympathetic drive translates into functional thermogenic activity, PPARγ-mediated recruitment is associated with a reduction in sympathetic activity leading to increased lipid storage in brown adipocytes. The promising therapeutic role of brown adipose tissue in the treatment of hypertriglyceridemic and hyperglycaemic conditions are also discussed.

  3. Browning of white adipose tissue uncouples glucose uptake from insulin signaling.

    Science.gov (United States)

    Mössenböck, Karin; Vegiopoulos, Alexandros; Rose, Adam J; Sijmonsma, Tjeerd P; Herzig, Stephan; Schafmeier, Tobias

    2014-01-01

    Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite) adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1) expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.

  4. The formation of brown adipose tissue induced by transgenic over-expression of PPARγ2.

    Science.gov (United States)

    Zhou, Ying; Yang, Jinzeng; Huang, Jinliang; Li, Ting; Xu, Dequan; Zuo, Bo; Hou, Liming; Wu, Wangjun; Zhang, Lin; Xia, Xiaoliang; Ma, Zhiyuan; Ren, Zhuqing; Xiong, Yuanzhu

    2014-04-18

    Brown adipose tissue (BAT) is specialized to dissipate energy as heat, therefore reducing fat deposition and counteracting obesity. Brown adipocytes arise from myoblastic progenitors during embryonic development by the action of transcription regulator PRDM16 binding to PPARγ, which promotes BAT-like phenotype in white adipose tissue. To investigate the capability of converting white adipose tissue to BAT or browning by PPARγ in vivo, we generated transgenic mice with over-expressed PPARγ2. The transgenic mice showed strong brown fat features in subcutaneous fat in morphology and histology. To provide molecular evidences on browning characteristics of the adipose tissue, we employed quantitative real-time PCR to determine BAT-specific gene expressions. The transgenic mice had remarkably elevated mRNA level of UCP1, Elovl3, PGC1α and Cebpα in subcutaneous fat. Compared with wild-type mice, UCP1 protein levels were increased significantly in transgenic mice. ATP concentration was slightly decreased in the subcutaneous fat of transgenic mice. Western blotting analysis also confirmed that phosphorylated AMPK and ACC proteins were significantly (P<0.01) increased in the transgenic mice. Therefore, this study demonstrated that over-expression of PPARγ2 in skeletal muscle can promote conversion of subcutaneous fat to brown fat formation, which can have beneficial effects on increasing energy metabolisms and combating obesity.

  5. Fat heaps

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; Katajainen, Jyrki

    This report is an electronic appendix to our paper \\Fat heaps without regular counters". In that paper we described a new variant of fat heaps that is conceptually simpler and easier to implement than the original version. We also compared the practical performance of this data structure...

  6. Comparison of pigment cell ultrastructure and organisation in the dermis of marble trout and brown trout, and first description of erythrophore ultrastructure in salmonids.

    Science.gov (United States)

    Djurdjevič, Ida; Kreft, Mateja Erdani; Sušnik Bajec, Simona

    2015-11-01

    Skin pigmentation in animals is an important trait with many functions. The present study focused on two closely related salmonid species, marble trout (Salmo marmoratus) and brown trout (S. trutta), which display an uncommon labyrinthine (marble-like) and spot skin pattern, respectively. To determine the role of chromatophore type in the different formation of skin pigment patterns in the two species, the distribution and ultrastructure of chromatophores was examined with light microscopy and transmission electron microscopy. The presence of three types of chromatophores in trout skin was confirmed: melanophores; xanthophores; and iridophores. In addition, using correlative microscopy, erythrophore ultrastructure in salmonids was described for the first time. Two types of erythrophores are distinguished, both located exclusively in the skin of brown trout: type 1 in black spot skin sections similar to xanthophores; and type 2 with a unique ultrastructure, located only in red spot skin sections. Morphologically, the difference between the light and dark pigmentation of trout skin depends primarily on the position and density of melanophores, in the dark region covering other chromatophores, and in the light region with the iridophores and xanthophores usually exposed. With larger amounts of melanophores, absence of xanthophores and presence of erythrophores type 1 and type L iridophores in the black spot compared with the light regions and the presence of erythrophores type 2 in the red spot, a higher level of pigment cell organisation in the skin of brown trout compared with that of marble trout was demonstrated. Even though the skin regions with chromatophores were well defined, not all the chromatophores were in direct contact, either homophilically or heterophilically, with each other. In addition to short-range interactions, an important role of the cellular environment and long-range interactions between chromatophores in promoting adult pigment pattern

  7. Production of Fat-1 transgenic chinese red steppe by somatic cell cloning%转Fat-1基因体细胞克隆草原红牛研究

    Institute of Scientific and Technical Information of China (English)

    康锦丹; 高威威; 高青山; 张立春

    2012-01-01

    Production of Fat-1 transgenic animal supplied the effective animal model for the study of the function of ω-3 polyunsaturated fatty acid.The study established the ear fibroblasts of Steppe Red Cattle and transfected the Fat-1 gene into them,then get the cloned transgenic cell.Make the transgenic cell as donor cell and the in vitro maturaed oocyte as nuclear receptor to reconstruct the transgenic blastula,compared the development of the non-transgenic and transgenic embryo.The results showed that the rate of reconstructed embryo was 26.04% and 26.04%,there was no significant difference(P〉0.05).Transferred the Fat-1 transgenic reconstructed morula or early embryo into the Uterus of Yanbian yellow cow,7 of them were pregnant but didn't develop to full term.%Fat-1基因的转基因动物克隆,为研究ω-3多不饱和脂肪酸的功能提供了高效、准确的医学、营养学动物模型。试验成功建立了草原红牛耳部成纤维细胞系,将Fat-1基因转染到草原红牛成纤维细胞,获得转基因阳性细胞克隆。以转基因细胞为核供体,体外成熟牛卵母细胞为核受体构建转基因克隆囊胚,比较未转基因与转基因克隆胚胎的体外发育情况。结果表明,体细胞重构胚体外囊胚率分别为26.04%和26.04%,两者之间无显差异著(P〉0.05)。转Fat-1基因的草原红牛重构桑葚胚或早期胚胎移植到延边黄牛子宫内,有7头妊娠,但没能够获得妊娠足月个体。

  8. Short communication: Altered expression of specificity protein 1 impairs milk fat synthesis in goat mammary epithelial cells.

    Science.gov (United States)

    Zhu, J J; Luo, J; Xu, H F; Wang, H; Loor, J J

    2016-06-01

    Specificity protein 1 (encoded by SP1) is a novel transcription factor important for the regulation of lipid metabolism and the normal function of various hormones in model organisms. Its potential role, if any, on ruminant milk fat is unknown. Despite the lower expression of the lipolysis-related gene ATGL (by 44 and 37% respectively), both the adenoviral overexpression and the silencing of SP1 [via short interfering (si)RNA] markedly reduced cellular triacylglycerol (TAG) content (by 28 and 25%, respectively), at least in part by decreasing the expression of DGAT1 (-36% in adenovirus treatment) and DGAT2 (-81 and -87%, respectively) that are involved in TAG synthesis. Consistent with the markedly lower expression of genes related to lipid droplet formation and secretion (TIP47 by 19 and 32%, and ADFP by 25 and 25%, respectively), cellular lipid droplet content was also decreased sharply, by 9 and 8.5%, respectively, after adenoviral overexpression of SP1 or its silencing via siRNA. Overall, the results underscored a potentially important role of SP1 in maintaining milk-fat droplet synthesis in goat mammary epithelial cells.

  9. Atmospheres of Brown Dwarfs

    CERN Document Server

    Helling, Christiane

    2014-01-01

    Brown Dwarfs are the coolest class of stellar objects known to date. Our present perception is that Brown Dwarfs follow the principles of star formation, and that Brown Dwarfs share many characteristics with planets. Being the darkest and lowest mass stars known makes Brown Dwarfs also the coolest stars known. This has profound implication for their spectral fingerprints. Brown Dwarfs cover a range of effective temperatures which cause brown dwarfs atmospheres to be a sequence that gradually changes from a M-dwarf-like spectrum into a planet-like spectrum. This further implies that below an effective temperature of < 2800K, clouds form already in atmospheres of objects marking the boundary between M-Dwarfs and brown dwarfs. Recent developments have sparked the interest in plasma processes in such very cool atmospheres: sporadic and quiescent radio emission has been observed in combination with decaying Xray-activity indicators across the fully convective boundary.

  10. Effects on markers of inflammation and endothelial cell function of three ad libitum diets differing in type and amount of fat and carbohydrate

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Larsen, Thomas Meinert; Due, Anette Pia;

    2011-01-01

    Diet is important for the prevention of CVD, and diets high in MUFA might be more cardioprotective than low-fat diets. We hypothesise that inflammation and endothelial cell function will be improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel...... randomised intervention trial on overweight individuals (aged 28·2 (sd 4·6) years) assigned to a diet moderate in the amount of fat (35-45% of energy; >20% of fat as MUFA; MUFA diet, n 39), a low-fat (20-30% of energy) diet (LF diet, n 43) or a control diet (35 % of energy as fat, n 24) for 6 months after...... weight loss. Protein constituted 10-20 % of energy in all diets. Food was provided free of charge. Fasting blood samples were collected before and after the intervention and analysed for C-reactive protein (CRP), IL-6, intercellular adhesion molecule, von Willebrand factor (vWF) and tissue factor pathway...

  11. A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study

    Science.gov (United States)

    Vinen, Catherine S; Turner, David R; Oliveira, David B G

    2004-01-01

    Administration of mercuric chloride (HgCl2) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl2 and then spontaneously resolve. If animals are re-challenged with HgCl2 6 weeks after initial exposure, they are resistant to autoimmunity, developing only attenuated disease. Recently, a separate phase of early caecal vasculitis was described beginning 24 h after initiating HgCl2 and prior to caecal entry of T cells. Previous work suggested this early vasculitis was αβ T-cell independent and implied a role for mast cells. We further tested this hypothesis by performing a histological study during the first 93 h following HgCl2 challenge defining the precise relationship between gut mast cell degranulation and appearing caecal vasculitis. We also studied whether early caecal vasculitis enters a resistant phase upon re-challenge with HgCl2. We show a direct correlation between mast cell degranulation and early caecal vasculitis following initial HgCl2 challenge. We demonstrate resistance to re-challenge in this phase of injury, with results at re-challenge also showing a correlation between mast cell degranulation and early caecal injury. PMID:15255970

  12. Fucose-containing sulfated polysaccharides from brown seaweeds inhibit proliferation of melanoma cells and induce apoptosis by activation of caspase-3 in vitro.

    Science.gov (United States)

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu; Mikkelsen, Jørn D; Meyer, Anne S

    2011-12-01

    Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds, especially brown macro-algae, are known to possess essential bioactive properties, notably growth inhibitory effects on tumor cells. In this work, we conducted a series of in vitro studies to examine the influence of FCSPs products from Sargassumhenslowianum C. Agardh (FSAR) and Fucus vesiculosus (FVES), respectively, on proliferation of melanoma B16 cells and to investigate the underlying apoptosis promoting mechanisms. Cell viability analysis showed that both FCSPs products, i.e., FSAR and FVES, decreased the proliferation of the melanoma cells in a dose-response fashion, with FSAR being more potent at lower dosages, and FVES being relatively more anti-proliferative than FSAR at higher dosages. Flow cytometric analysis by Annexin V staining of the melanoma cells exposed to the FCSPs products confirmed that both FSAR and FVES induced apoptosis. The FCSPs-induced apoptosis was evidenced by loss of plasma membrane asymmetry and translocation of the cell membrane phospholipids and was accompanied by the activation of caspase-3. The FCSPs bioactivity is proposed to be attributable to distinct structural features of the FCSPs, particularly the presence of sulfated galactofucans (notably in S.henslowianum) and sulfated fucans (notably in F. vesiculosus). This study thus indicates that unfractionated FCSPs may exert bioactive effects on skin cancer cells via induction of apoptosis through cascades of reactions that involve activation of caspase-3.

  13. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    Science.gov (United States)

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. PMID:26884438

  14. Role of Receptor-Interacting Protein 140 in human fat cells

    Directory of Open Access Journals (Sweden)

    Stenson Britta M

    2010-01-01

    Full Text Available Abstract Background Mice lacking Receptor-interacting protein 140 (RIP140 have reduced body fat which at least partly is mediated through increased lipid and glucose metabolism in adipose tissue. In humans, RIP140 is lower expressed in visceral white adipose tissue (WAT of obese versus lean subjects. We investigated the role of RIP140 in human subcutaneous WAT, which is the major fat depot of the body. Methods Messenger RNA levels of RIP140 were measured in samples of subcutaneous WAT from women with a wide variation in BMI and in different human WAT preparations. RIP140 mRNA was knocked down with siRNA in in vitro differentiated adipocytes and the impact on glucose transport and mRNA levels of target genes determined. Results RIP140 mRNA levels in subcutaneous WAT were decreased among obese compared to lean women and increased by weight-loss, but did not associate with mitochondrial DNA copy number. RIP140 expression increased during adipocyte differentiation in vitro and was higher in isolated adipocytes compared to corresponding pieces of WAT. Knock down of RIP140 increased basal glucose transport and mRNA levels of glucose transporter 4 and uncoupling protein-1. Conclusions Human RIP140 inhibits glucose uptake and the expression of genes promoting energy expenditure in the same fashion as the murine orthologue. Increased levels of human RIP140 in subcutaneous WAT of lean subjects may contribute to economize on energy stores. By contrast, the function and expression pattern does not support that RIP140 regulate human obesity.

  15. Analyzing Serum-Stimulated Prostate Cancer Cell Lines After Low-Fat, High-Fiber Diet and Exercise Intervention

    Directory of Open Access Journals (Sweden)

    Sherry Soliman

    2011-01-01

    Full Text Available Serum from men undergoing a low-fat, high-fiber diet and exercise intervention has previously been shown to decrease growth and increase apoptosis in serum-stimulated, androgen-dependent LNCaP cells associated with a reduction in serum IGF-I. Here we sought to determine the underlying mechanisms for these anticancer effects. Again, the intervention slowed growth and increased apoptosis in LNCaP cells; responses that were eliminated when IGF-I was added back to the post-intervention samples. The p53 protein content was increased and NFκB activation reduced in the post serum-stimulated LNCaP cells. Similar results were observed when the IGF-I receptor was blocked in the pre-intervention serum. In androgen-independent PC-3 cells, growth was reduced while none of the other factors were changed by the intervention. We conclude that diet and exercise intervention might help prevent clinical PCa as well as aid in the treatment of PCa during the early stages of development.

  16. AHNAK deficiency promotes browning and lipolysis in mice via increased responsiveness to β-adrenergic signalling

    OpenAIRE

    Jae Hoon Shin; Seo Hyun Lee; Yo Na Kim; Il Yong Kim; Youn Ju Kim; Dong Soo Kyeong; Hee Jung Lim; Soo Young Cho; Junhee Choi; Young Jin Wi; Jae-Hoon Choi; Yeo Sung Yoon; Yun Soo Bae; Je Kyung Seong

    2016-01-01

    In adipose tissue, agonists of the β3-adrenergic receptor (ADRB3) regulate lipolysis, lipid oxidation, and thermogenesis. The deficiency in the thermogenesis induced by neuroblast differentiation-associated protein AHNAK in white adipose tissue (WAT) of mice fed a high-fat diet suggests that AHNAK may stimulate energy expenditure via development of beige fat. Here, we report that AHNAK deficiency promoted browning and thermogenic gene expression in WAT but not in brown adipose tissue of mice ...

  17. Function and cancer genomics of FAT family genes

    OpenAIRE

    KATOH, MASARU

    2012-01-01

    FAT1, FAT2, FAT3 and FAT4 are human homologs of Drosophila Fat, which is involved in tumor suppression and planar cell polarity (PCP). FAT1 and FAT4 undergo the first proteolytic cleavage by Furin and are predicted to undergo the second cleavage by γ-secretase to release intracellular domain (ICD). Ena/VAPS-binding to FAT1 induces actin polymerization at lamellipodia and filopodia to promote cell migration, while Scribble-binding to FAT1 induces phosphorylation and functional inhibition of YA...

  18. Control and Physiological Determinants of Sympathetically Mediated Brown Adipose Tissue Thermogenesis

    OpenAIRE

    DenisRichard; ÉricTurcotte

    2012-01-01

    Brown adipose tissue (BAT) represents a remarkable heat-producing tissue. The thermogenic potential of BAT is conferred by uncoupling protein 1, a protein found uniquely in the brown adipocytes. The physiological control of BAT activity and capacity is ensured by the sympathetic nervous system (SNS), which densely innervates brown fat depots. SNS-mediated BAT thermogenesis is essentially governed by hypothalamic and brainstem neurons. BAT is not only controlled by the brain thermoregulatory c...

  19. Turning up the heat : role of brown adipose tissue in metabolic disease

    NARCIS (Netherlands)

    Boon, Mariëtte Rebecca

    2014-01-01

    In 1551, the Swiss naturalist Konrad Gessner first described brown adipose tissue (BAT) as being “neither fat, nor flesh (nec pinguitudo, nec caro), but something in between”. Now, some 460 years later, we know that Gessner had guessed the origin of brown adipocytes correctly. A unique property of t

  20. The cell size and distribution of adipocytes from subcutaneous and visceral fat is associated with type 2 diabetes mellitus in humans

    OpenAIRE

    Fang, Lingling; Guo, Fangjian; ZHOU, LIHUA; Stahl, Richard; Grams, Jayleen

    2015-01-01

    Aims/hypothesis: Regional deposition of adipose tissue and adipocyte morphology may contribute to increased risk for insulin resistance. The aim of this study was to compare adipocyte cell size and size distribution from multiple fat depots and to determine the association with type 2 diabetes mellitus, anthropomorphic data, and subjects' metabolic profile.

  1. A precise, low-cost milk sampler to enable the analysis of fat, protein, lactose and somatic cells in milk from individual cows

    NARCIS (Netherlands)

    Clarke, T.; Hannah, M.C.; Wientjes, H.A.

    2007-01-01

    Less than half of Australian dairy farmers undertake production recording that normally requires the collection of milk samples for the measurements of fat, protein and lactose percentages and somatic cell count. Usually the milk samples are collected from individual animals on a `one-day-per-month¿

  2. FATS 在非小细胞肺癌组织中的表达及临床相关性研究%Expression and Clinical Significance of FATS in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    闫双双; 田寅; 张军; 仇丽; 马克; 李政

    2012-01-01

    目的:研究脆性位点相关抑癌基因(fraglie-site associated tumor suppressor,FATS)在非小细胞肺癌以及癌旁正常组织的mRNA和蛋白表达水平,探讨FATS在非小细胞肺癌发生发展中的作用.方法:通过实时定量PCR技术和Western blot技术分析检测天津医科大学附属肿瘤医院2003年5月至2007年10月间91例非小细胞肺癌患者FATS基因和蛋白表达水平,并且研究其表达水平与患者临床预后的关系.结果:实时定量PCR和Western blot结果均显示非小细胞肺癌患者肿瘤组织FATS表达量明显低于其配对的癌旁正常组织(P=0.001).FATS基因低表达患者与高表达患者在总生存期差异有统计学意义(P=0.030).Cox多因素分析显示FATS基因的表达是非小细胞肺癌独立的预后因素(OR=2.250;95%CI:1.054~4.805;P=0.036).结论:FATS低表达与非小细胞肺癌的发生发展具有高度相关性,FATS表达作为非小细胞肺癌的独立预后因素,有望成为新的肿瘤标记物,为临床诊治提供新的靶点.%Objective: To compare the levels of FATS mRNA and protein in non-small cell lung cancer ( NSCLC ) and paired normal tissues and to investigate the function of FATS in NSCLC. Methods: The mRNA and protein expression levels of the FATS gene in 91 NSCLC patients were determined using quantitative real-time reverse transcription PCR ( qRT-PCR ) and Western blot analysis. The relationship between FATS expression and the prognosis of these patients was investigated. Results: The qRT-PCR and Western blot analysis showed that FATS expression was significantly lower in NSCLC tissue than in the paired paraneoplastic tissue ( P = 0.001 ). The differences in the overall survival of patients with low and high FATS expression were statistically significant ( P = 0.030 ). Multivariate analysis indicated that the FATS expression was an independent prognostic factor for NSCLC ( odds ratio, 2.250; 95% confidence interval, 1.054-4.805; P = 0.036 ). Conclusion

  3. Cell Suspension Culture of Eriobotrya japonica Regulates the Diabetic and Hyperlipidemic Signs of High-Fat-Fed Mice

    Directory of Open Access Journals (Sweden)

    Jin-Bin Wu

    2013-03-01

    Full Text Available The present study investigates the anti-hyperlipidemic and antihyperglycemic effects and mechanism in high-fat (HF-fed mice of cell suspension culture of Eriobotrya japonica (TA, which contains a great number of pentacyclic terpenoids. Firstly, C57BL/6J mice were randomly divided into two groups: the control (CON group was fed with a low-fat diet (n = 9, whereas the experimental group was fed a 45% HF diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and was orally given TA or rosiglitazone or not for 4 weeks. Blood and visceral adipose tissue, liver tissue and skeletal muscle were examined. Treatment with TA reduced body weight gain, weights of white adipose tissue (WAT (including epididymal, perirenal, mesenteric WAT and visceral fat, and hepatic triacylglycerol content significantly without affecting food intake in diet-induced diabetic mice. TA effectively prevented HF diet-induced increases in the levels of blood glucose, insulin, leptin and HOMA-IR index (p < 0.001, p < 0.05, p < 0.05, p < 0.01, respectively and attenuated insulin resistance. Treatment with TA, adipocytes in the visceral depots showed a reduction in size. TA effectively significantly increased the protein contents of phosphorylation of AMPK-α (Thr172 both in liver and adipose tissue. It is shown that TA exhibits hypolipidemic effect in HF-fed mice by decreasing gene expressions of fatty acid synthesis, including acyl-coenzyme A: diacylglycerol acyltransferase (DGAT 2, which catalyzes the final step in the synthesis of triglycerides, and antidiabetic properties occurred as a result of decreased hepatic glucose production via phosphenolpyruvate carboxykinase (PEPCK down- regulation, improved insulin sensitization and TA (at 1.0 g/kg dose decreased expression of hepatic and adipose 11-β-hydroxysteroid dehydroxygenase (11β-HSD1 gene, which contributed in attenuating diabetic state. Futhermore, TA at

  4. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    Science.gov (United States)

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release. PMID:27454856

  5. Carbon nanotube-based substrates promote cardiogenesis in brown adipose-derived stem cells via β1-integrin-dependent TGF-β1 signaling pathway

    Science.gov (United States)

    Sun, Hongyu; Mou, Yongchao; Li, Yi; Li, Xia; Chen, Zi; Duval, Kayla; Huang, Zhu; Dai, Ruiwu; Tang, Lijun; Tian, Fuzhou

    2016-01-01

    Stem cell-based therapy remains one of the promising approaches for cardiac repair and regeneration. However, its applications are restricted by the limited efficacy of cardiac differentiation. To address this issue, we examined whether carbon nanotubes (CNTs) would provide an instructive extracellular microenvironment to facilitate cardiogenesis in brown adipose-derived stem cells (BASCs) and to elucidate the underlying signaling pathways. In this study, we systematically investigated a series of cellular responses of BASCs due to the incorporation of CNTs into collagen (CNT-Col) substrates that promoted cell adhesion, spreading, and growth. Moreover, we found that CNT-Col substrates remarkably improved the efficiency of BASCs cardiogenesis by using fluorescence staining and quantitative real-time reverse transcription-polymerase chain reaction. Critically, CNTs in the substrates accelerated the maturation of BASCs-derived cardiomyocytes. Furthermore, the underlying mechanism for promotion of BASCs cardiac differentiation by CNTs was determined by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction, and Western blotting assay. It is notable that β1-integrin-dependent TGF-β1 signaling pathway modulates the facilitative effect of CNTs in cardiac differentiation of BASCs. Therefore, it is an efficient approach to regulate cardiac differentiation of BASCs by the incorporation of CNTs into the native matrix. Importantly, our findings can not only facilitate the mechanistic understanding of molecular events initiating cardiac differentiation in stem cells, but also offer a potentially safer source for cardiac regenerative medicine. PMID:27660434

  6. Porcine adipose-derived stem cells from buccal fat pad and subcutaneous adipose tissue for future preclinical studies in oral surgery

    OpenAIRE

    Niada, S; L.M. Ferreira; Arrigoni, E.; Addis, A.; M. Campagnol; E. Broccaioli; Brini, A T

    2013-01-01

    Introduction Adipose-derived stem cells (ASCs) are progenitor cells used in bone tissue engineering and regenerative medicine. Despite subcutaneous adipose tissue being more abundant, the buccal fat pad (BFP) is easily accessible for dentists and maxillofacial surgeons. For this reason, considering the need for preclinical study and the swine as an optimal animal model in tissue engineering applications, we compared the features of porcine ASCs (pASCs) from both tissue-harvesting sites. Metho...

  7. NOX1-induced accumulation of reactive oxygen species in abdominal fat-derived mesenchymal stromal cells impinges on long-term proliferation

    OpenAIRE

    Sela, M; Tirza, G; Ravid, O; Volovitz, I; Solodeev, I; Friedman, O; Zipori, D; E. Gur; Krelin, Y; Shani, N

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and can be derived from different adult tissues including fat. Our repeated attempts to produce long-term proliferative cultures of rat abdominal adipose stem cells (aASCs) under normal oxygen concentration (21%) were unsuccessful. We set to examine the events controlling this cytostasis of aASCs and found that it resulted from overproduction of reactive oxygen species (ROS) that led to apoptosis. ROS overproduction in aASCs was accompanied by ...

  8. Adverse Fat Depots and Marrow Adiposity Are Associated with Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation

    OpenAIRE

    MOSTOUFI-MOAB, SOGOL; Magland, Jeremy; Isaacoff, Elizabeth J.; Sun, Wenli; Rajapakse, Chamith S.; Zemel, Babette; Wehrli, Felix; Shekdar, Karuna; Baker, Joshua; Long, Jin; Leonard, Mary B.

    2015-01-01

    Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12–25 years) a median of 9.7 (4...

  9. Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

    Energy Technology Data Exchange (ETDEWEB)

    An, Lei, E-mail: anleim@yahoo.com.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Pang, Yun-Wei, E-mail: yunweipang@126.com [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Gao, Hong-Mei, E-mail: Gaohongmei_123@yahoo.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki-Iwama 319-0206 (Japan); Tao, Li, E-mail: Eunice8023@yahoo.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin 130118 (China); Miao, Kai, E-mail: miaokai7@163.com [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Wu, Zhong-Hong, E-mail: wuzhh@cau.edu.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); and others

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. Black-Right-Pointing-Pointer fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. Black-Right-Pointing-Pointer fat-1 reduces lipid deposition in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlled experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.

  10. Ascorbate-dependent impact on cell-derived matrix in modulation of stiffness and rejuvenation of infrapatellar fat derived stem cells toward chondrogenesis.

    Science.gov (United States)

    Pizzute, Tyler; Zhang, Ying; He, Fan; Pei, Ming

    2016-08-10

    Developing an in vitro microenvironment using cell-derived decellularized extracellular matrix (dECM) is a promising approach to efficiently expand adult stem cells for cartilage engineering and regeneration. Ascorbic acid serves as a critical stimulus for cells to synthesize collagens, which constitute the major component of dECM. In this study, we hypothesized that optimization of ascorbate treatment would maximize the rejuvenation effect of dECM on expanded stem cells from human infrapatellar fat pad in both proliferation and chondrogenic differentiation. In the duration regimen study, we found that dECM without L-ascorbic acid phosphate (AA) treatment, exhibiting lower stiffness measured by atomic force microscopy, yielded expanded cells with higher proliferation capacity but lower chondrogenic potential when compared to those with varied durations of AA treatment. dECM with 250 µM of AA treatment for 10 d had better rejuvenation in chondrogenic capacity if the deposited cells were from passage 2 rather than passage 5, despite no significant difference in matrix stiffness. In the dose regimen study, we found that dECMs deposited by varied concentrations of AA yielded expanded cells with higher proliferation capacity despite lower expression levels of stem cell related surface markers. Compared to cells expanded on tissue culture polystyrene, those on dECM exhibited greater chondrogenic potential, particularly for the dECMs with 50 µM and 250 µM of AA treatment. With the supplementation of ethyl-3,4-dihydroxybenzoate (EDHB), an inhibitor targeting procollagen synthesis, the dECM with 50 µM of AA treatment exhibited a dramatic decrease in the rejuvenation effect of expanded cell chondrogenic potential at both mRNA and protein levels despite no significant difference in matrix stiffness. Defined AA treatments during matrix preparation will benefit dECM-mediated stem cell engineering and future treatments for cartilage defects.

  11. Ascorbate-dependent impact on cell-derived matrix in modulation of stiffness and rejuvenation of infrapatellar fat derived stem cells toward chondrogenesis.

    Science.gov (United States)

    Pizzute, Tyler; Zhang, Ying; He, Fan; Pei, Ming

    2016-01-01

    Developing an in vitro microenvironment using cell-derived decellularized extracellular matrix (dECM) is a promising approach to efficiently expand adult stem cells for cartilage engineering and regeneration. Ascorbic acid serves as a critical stimulus for cells to synthesize collagens, which constitute the major component of dECM. In this study, we hypothesized that optimization of ascorbate treatment would maximize the rejuvenation effect of dECM on expanded stem cells from human infrapatellar fat pad in both proliferation and chondrogenic differentiation. In the duration regimen study, we found that dECM without L-ascorbic acid phosphate (AA) treatment, exhibiting lower stiffness measured by atomic force microscopy, yielded expanded cells with higher proliferation capacity but lower chondrogenic potential when compared to those with varied durations of AA treatment. dECM with 250 µM of AA treatment for 10 d had better rejuvenation in chondrogenic capacity if the deposited cells were from passage 2 rather than passage 5, despite no significant difference in matrix stiffness. In the dose regimen study, we found that dECMs deposited by varied concentrations of AA yielded expanded cells with higher proliferation capacity despite lower expression levels of stem cell related surface markers. Compared to cells expanded on tissue culture polystyrene, those on dECM exhibited greater chondrogenic potential, particularly for the dECMs with 50 µM and 250 µM of AA treatment. With the supplementation of ethyl-3,4-dihydroxybenzoate (EDHB), an inhibitor targeting procollagen synthesis, the dECM with 50 µM of AA treatment exhibited a dramatic decrease in the rejuvenation effect of expanded cell chondrogenic potential at both mRNA and protein levels despite no significant difference in matrix stiffness. Defined AA treatments during matrix preparation will benefit dECM-mediated stem cell engineering and future treatments for cartilage defects. PMID:27508528

  12. Adipose-derived mesenchymal stem cells promote the survival of fat grafts via crosstalk between the Nrf2 and TLR4 pathways.

    Science.gov (United States)

    Chen, Xiaosong; Yan, Liu; Guo, Zhihui; Chen, Zhaohong; Chen, Ying; Li, Ming; Huang, Chushan; Zhang, Xiaoping; Chen, Liangwan

    2016-01-01

    Autologous fat grafting is an effective reconstructive surgery technique; however, its success is limited by inconsistent graft retention and an environment characterized by high oxidative stress and inflammation. Adipose-derived stem cells (ADSCs) increase the survival of fat grafts, although the underlying mechanisms remain unclear. Here, TLR4(-/-) and Nrf2(-/-) mice were used to explore the effects of oxidative stress and inflammation on the viability and function of ADSCs in vitro and in vivo. Enrichment of fat grafts with ADSCs inhibited inflammatory cytokine production, enhanced growth factor levels, increased fat graft survival, downregulated NADPH oxidase (NOX)1 and 4 expression, increased vascularization and reduced ROS production in a manner dependent on toll-like receptor (TLR)-4 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Immunohistochemical analysis showed that exposure to hypoxia enhanced ADSC growth and promoted the differentiation of ADSCs into vascular endothelial cells. Hypoxia-induced inflammatory cytokine, growth factor and NOX1/4 upregulation, as well as increased ROS production and apoptosis in ADSCs were dependent on TLR4 and Nrf2, which also modulated the effect of ADSCs on promoting endothelial progenitor cell migration and angiogenesis. Western blot analyses showed that the effects of hypoxia on ADSCs were regulated by crosstalk between Nrf2 antioxidant responses and NF-κB- and TLR4-mediated inflammatory responses. Taken together, our results indicate that ADSCs can increase the survival of fat transplants through the modulation of inflammatory and oxidative responses via Nrf2 and TLR4, suggesting potential strategies to improve the use of ADSCs for cell therapy. PMID:27607584

  13. Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes

    Indian Academy of Sciences (India)

    Finny Monickaraj; Sankaramoorthy Aravind; Pichamoorthy Nandhini; Paramasivam Prabu; Chandrakumar Sathishkumar; Viswanathan Mohan; Muthuswamy Balasubramanyam

    2013-03-01

    Telomere shortening is emerging as a biological indicator of accelerated aging and aging-related diseases including type 2 diabetes. While telomere length measurements were largely done in white blood cells, there is lack of studies on telomere length in relation to oxidative stress in target tissues affected in diabetes. Therefore, the aim of this study is to induct oxidative stress in adipocytes and to test whether these adipocytes exhibit shortened telomeres, senescence and functional impairment. 3T3-L1 adipocytes were subjected to oxidative stress and senescence induction by a variety of means for 2 weeks (exogenous application of H2O2, glucose oxidase, asymmetric dimethylarginine (ADMA) and glucose oscillations). Cells were probed for reactive oxygen species generation (ROS), DNA damage, mRNA and protein expression of senescent and pro-inflammatory markers, telomere length and glucose uptake. Compared to untreated cells, both ROS generation and DNA damage were significantly higher in cells subjected to oxidative stress and senescence. Adipocytes subjected to oxidative stress also showed shortened telomeres and increased mRNA and protein expression of p53, p21, TNF and IL-6. Senescent cells were also characterized by decreased levels of adiponectin and impaired glucose uptake. Briefly, adipocytes under oxidative stress exhibited increased ROS generation, DNA damage, shortened telomeres and switched to senescent/pro-inflammatory phenotype with impaired glucose uptake.

  14. Bone marrow fat.

    Science.gov (United States)

    Hardouin, Pierre; Pansini, Vittorio; Cortet, Bernard

    2014-07-01

    Bone marrow fat (BMF) results from an accumulation of fat cells within the bone marrow. Fat is not a simple filling tissue but is now considered as an actor within bone microenvironment. BMF is not comparable to other fat depots, as in subcutaneous or visceral tissues. Recent studies on bone marrow adipocytes have shown that they do not appear only as storage cells, but also as cells secreting adipokines, like leptin and adiponectin. Moreover bone marrow adipocytes share the same precursor with osteoblasts, the mesenchymal stem cell. It is now well established that high BMF is associated with weak bone mass in osteoporosis, especially during aging and anorexia nervosa. But numerous questions remain discussed: what is the precise phenotype of bone marrow adipocytes? What is the real function of BMF, and how does bone marrow adipocyte act on its environment? Is the increase of BMF during osteoporosis responsible for bone loss? Is BMF involved in other diseases? How to measure BMF in humans? A better understanding of BMF could allow to obtain new diagnostic tools for osteoporosis management, and could open major therapeutic perspectives. PMID:24703396

  15. Fat-1基因真核表达载体的构建及其对人口腔鳞癌细胞脂肪酸含量的影响%Construction of Fat-1 Eukaryotic Expression Vector and Its Effect on Fatty Acids Content of Human Oral Squamous Cell Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    李栋; 聂代邦; 王海军; 段新平; 逄大欣; 欧阳红生

    2011-01-01

    目的:构建真核表达载体 pcDNA3.1-Fat1,线性化稳定转染人口腔鳞癌细胞株Tca8113,检测其细胞内脂肪酸含量变化.方法:通过重叠延伸PCR方法人工合成利于真核表达的Fat-1基因,用基因重组技术构建真核表达载体pcDNA3.1-Fat-1,用脂质体转染真核细胞的方法转染人口腔鳞癌细胞株Tca8113,用气相色谱仪检测脂肪酸的变化情况.结果:测序及酶切鉴定成功合成真核偏好表达的Fat-1基因.与对照组相比,转染Fat-1基因的口腔癌细胞的n-3脂肪酸明显增多,n-6/n-3明显下降.结论:成功构建真核表达载体 pcDNA3.1-Fat1,并对口腔鳞癌细胞内脂肪酸含量产生明显影响,为进一步研究Fat-1基因在口腔鳞癌中的生物学功能奠定了基础.%Objective: To construct eukaryotic expression vector pcDNA3.1-Fat1 and transfect human oral squamous cell carcinoma cell line Tca8113, then tested the changes of fatty acids content in Tca8113.Methods: The Fat-1 gene was constructed by SOE-PCR.The pcDNA3.1-Fat1 was constructed by using recombinant DNA technology, human oral squamous carcinoma cells line Tca8113cells was transfected using lipofection method.The fatty acids content of the transfected Tca8113 cells was detected by using gas chromatography technology.Results: Eukaryotic expression vector pcDNA3.l-Fatl was successfully constructed and transfected into human oral squamous carcinoma cell lineTca8113.The cells that expressed the fat-1 gene had a lower n-6/n-3 PUFA ratio compared with the cells that expressed the control vector.Conclusion: The pcDNA3.1-Fat1 is successfully constructed, and it has significant effect on the PUFAs content of Tca8113 cells, which makes a foundation in the future study on the biological function of Fat-1 gene in human oral squamous carcinoma.

  16. Father Brown, Selected sories

    NARCIS (Netherlands)

    Chesterton, G.K.

    2005-01-01

    Father Brown, a small, round Catholic priest with a remarkable understanding of the criminal mind, is one of literature's most unusual and endearing detectives, able to solve the strangest crimes in a most fascinating manner. This collection draws from all five Father Brown books, and within their r

  17. A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

    Energy Technology Data Exchange (ETDEWEB)

    Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Tautenhahn, Hans-Michael, E-mail: hans-michael.tautenhahn@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany); Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [University Hospital Ulm, First Department of Medicine, Albert-Einstein-Allee 23, Ulm D-89081 (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany)

    2014-02-15

    Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte

  18. A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

    International Nuclear Information System (INIS)

    Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte

  19. Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

    NARCIS (Netherlands)

    A. Grefhorst (Aldo); J.C. van den Beukel (Johanna); A.F. van Houten (A.); J. Steenbergen (Jacobie); J.A. Visser (Jenny); A.P.N. Themmen (Axel)

    2015-01-01

    textabstractBackground: In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed

  20. Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy.

    Science.gov (United States)

    Mori, Marcelo A; Thomou, Thomas; Boucher, Jeremie; Lee, Kevin Y; Lallukka, Susanna; Kim, Jason K; Torriani, Martin; Yki-Järvinen, Hannele; Grinspoon, Steven K; Cypess, Aaron M; Kahn, C Ronald

    2014-08-01

    miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and "whitening" of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte-like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy.

  1. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease - can it differentiate bone infarcts from acute osteomyelitis?

    International Nuclear Information System (INIS)

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children. (orig.)

  2. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease - can it differentiate bone infarcts from acute osteomyelitis?

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, Jorge; Bedoya, Maria A. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Green, Abby M. [The Children' s Hospital of Philadelphia, Division of Oncology, Philadelphia, PA (United States); Jaramillo, Diego; Ho-Fung, Victor [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States)

    2015-12-15

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children. (orig.)

  3. Qualitative and quantitative analysis of rabbit's fat mesenchymal stem cells Análise quantitativa e qualitativa de células tronco mesênquimais da gordura de coelhos

    OpenAIRE

    Marcelo Paulo Vaccari Mazzetti; Isis Sousa Oliveira; Regiane Miranda-Ferreira; Grasiele Fauaz; Chaibe Nunes Ribeiro; Paulo de Oliveira Gomes; Paulo Pontes; Alice Teixeira Ferreira; Lilian Piñero Eça

    2010-01-01

    PURPOSE: To present an experimental model of qualitative and quantitative analysis of mesenchymal stem cells from fat of rabbits obtained by lipectomy. The fat could be a great source for obtaining mesenchymal stem cells and to create conditions for repairing injured tissues by bioengineering. METHODS: New Zealand rabbits (n= 10) adipose panicle (2-3 cm) were removed by lipectomy, fragmented and washed with PBS and enzymatically dissociated with trypsin/EDTA. Lately, these cells were incubate...

  4. Cell proliferation and neuroblast differentiation in the dentate gyrus of high-fat diet-fed mice are increased after rosiglitazone treatment.

    Science.gov (United States)

    Yoo, Dae Young; Kim, Woosuk; Kim, Dae Won; Nam, Sung Min; Jung, Hyo Young; Kim, Jong Whi; Lee, Choong Hyun; Choi, Jung Hoon; Won, Moo-Ho; Yoon, Yeo Sung; Hwang, In Koo

    2014-01-01

    In this study, we determined how rosiglitazone (RSG) differentially affected hippocampal neurogenesis in mice fed a low-fat diet (LFD) or high-fat diet (HFD; 60% fat). LFD and HFD were given to the mice for 8 weeks. Four weeks after initiating the LFD and HFD feeding, vehicle or RSG was administered orally once a day to both groups of mice. We measured cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus using Ki67 and doublecortin (DCX), respectively, as markers. In addition, we monitored the effects of RSG on the levels of DCX and brain-derived neurotrophic factor (BDNF) in hippocampal homogenates. At 8 weeks after the LFD feeding, the numbers of Ki67- and DCX-positive cells as well as hippocampal levels of DCX and BDNF were significantly decreased in the RSG-treated group compared to the vehicle-treated animals. In contrast, the numbers of Ki67- and DCX-positive cells along with hippocampal levels of DCX and BDNF in the HFD fed mice were significantly increased in the RSG-treated mice compared to the vehicle-treated group. Our data demonstrate that RSG can modulate the levels of BDNF, which could play a pivotal role in cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus.

  5. Emulsion Mapping in Pork Meat Emulsion Systems with Various Lipid Types and Brown Rice Fiber

    OpenAIRE

    Choi, Yun-Sang; Kim, Young-Boong; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Jeong, Tae-Jun; Park, Jinhee; Kim, Cheon-Jei

    2015-01-01

    This study was conducted to evaluate emulsion mapping between emulsion stability and cooking yields, apparent viscosity, and hardness of reduced-fat pork emulsion systems. The reduced-fat emulsion systems were supplemented with different lipid types and brown rice bran fiber (BRF) concentrations. Compared to the control with 30% back fat, lower emulsion stability and higher cooking yield of meat emulsion systems were observed in T1 (30% back fat+1% BRF), T2 (30% back fat+2% BRF), T3 (30% back...

  6. The Effect of Sulfated (1→3-α-l-Fucan from the Brown Alga Saccharina cichorioides Miyabe on Resveratrol-Induced Apoptosis in Colon Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Olesia S. Vishchuk

    2013-01-01

    Full Text Available Accumulating data clearly indicate that the induction of apoptosis by nontoxic natural compounds is a potent defense against the development and progression of many malignancies, including colon cancer. Resveratrol and the fucoidans have been shown to possess potent anti-tumor activity in vitro and in vivo. The aim of the present study was to examine whether the combination of a fucoidan from the brown alga Saccharina cichorioides Miyabe and resveratrol would be an effective preventive and/or therapeutic strategy against colon cancer. Based on NMR spectroscopy and MALDI-TOF analysis, the fucoidan isolated and purified from Saccharina cichorioides Miyabe was (1→3-α-l-fucan with sulfate groups at C2 and C4 of the α-l-fucopyranose residues. The fucoidan enhanced the antiproliferative activity of resveratrol at nontoxic doses and facilitated resveratrol-induced apoptosis in the HCT 116 human colon cancer cell line. Apoptosis was realized by the activation of initiator caspase-9 and effector caspase-7 and -3, followed by the cleavage of PARP. Furthermore, significant inhibition of HCT 116 colony formation was associated with the sensitization of cells to resveratrol by the fucoidan. Taken together, these results demonstrate that the combination of the algal fucoidan with resveratrol may provide a potential therapy against human colon cancer.

  7. Increased atherosclerosis and vascular smooth muscle cell activation in AIF-1 transgenic mice fed a high-fat diet.

    Science.gov (United States)

    Sommerville, Laura J; Kelemen, Sheri E; Ellison, Stephen P; England, Ross N; Autieri, Michael V

    2012-01-01

    Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, scaffold signal transduction protein constitutively expressed in inflammatory cells, but inducible in vascular smooth muscle cells (VSMCs) in response to injury or inflammatory stimuli. Although several basic science and population studies have reported increased AIF-1 expression in human and experimental atherosclerosis, a direct causal effect of AIF-1 expression on development of atherosclerosis has not been reported. The purpose of this study is to establish a direct relationship between AIF-1 expression and development of atherosclerosis. AIF-1 expression is detected VSMC in atherosclerotic lesions from ApoE(-/-) mice, but not normal arteries from wild-type mice. AIF-1 expression can be induced in cultured VSMC by stimulation with oxidized LDL (ox-LDL). Transgenic mice in which AIF-1 expression is driven by the G/C modified SM22 alpha promoter to restrict AIF-1 expression to VSMC develop significantly increased atherosclerosis compared with wild-type control mice when fed a high-fat diet (P=0.022). Cultured VSMC isolated from Tg mice demonstrated significantly increased migration in response to ox-LDL compared with matched controls (P<0.001). VSMC isolated from Tg mice and cultured human VSMC which over express AIF-1 demonstrated increased expression of MMP-2 and MMP-9 mRNA and protein and increased NF-κB activation in response to ox-LDL as compared with wild-type control mice. VSMC which over express AIF-1 have significantly increased uptake of ox-LDL, and increased CD36 expression. Together, these data suggest a strong association between AIF-1 expression, NF-κB activation, and development of experimental atherosclerosis.

  8. Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis.

    Science.gov (United States)

    Rydén, Mikael; Jocken, Johan; van Harmelen, Vanessa; Dicker, Andrea; Hoffstedt, Johan; Wirén, Mikael; Blomqvist, Lennart; Mairal, Aline; Langin, Dominique; Blaak, Ellen; Arner, Peter

    2007-06-01

    Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) regulate adipocyte lipolysis in rodents. The purpose of this study was to compare the roles of these lipases for lipolysis in human adipocytes. Subcutaneous adipose tissue was investigated. HSL and ATGL protein expression were related to lipolysis in isolated mature fat cells. ATGL or HSL were knocked down by RNA interference (RNAi) or selectively inhibited, and effects on lipolysis were studied in differentiated preadipocytes or adipocytes derived from human mesenchymal stem cells (hMSC). Subjects were all women. There were 12 lean controls, 8 lean with polycystic ovary syndrome (PCOS), and 27 otherwise healthy obese subjects. We found that norepinephrine-induced lipolysis was positively correlated with HSL protein levels (P < 0.0001) but not with ATGL protein. Women with PCOS or obesity had significantly decreased norepinephrine-induced lipolysis and HSL protein expression but no change in ATGL protein expression. HSL knock down by RNAi reduced basal and catecholamine-induced lipolysis. Knock down of ATGL decreased basal lipolysis but did not change catecholamine-stimulated lipolysis. Treatment of hMSC with a selective HSL inhibitor during and/or after differentiation in adipocytes reduced basal lipolysis by 50%, but stimulated lipolysis was inhibited completely. In contrast to findings in rodents, ATGL is of less importance than HSL in regulating catecholamine-induced lipolysis and cannot replace HSL when this enzyme is continuously inhibited. However, both lipases regulate basal lipolysis in human adipocytes. ATGL expression, unlike HSL, is not influenced by obesity or PCOS. PMID:17327373

  9. DNA DAMAGE AND EXTERNAL LESIONS IN BROWN BULLHEAD FROM CONTAMINATED HABITATS

    Science.gov (United States)

    The single cell gel electrophoresis ("Comet") assay was used to compare levels of DNA damage in brown bullheads (Ameiurus nebulosus) collected from three known contaminated locations, the Cuyahoga River, Ashtabula River, and Ashumet Pond (Cape Cod), with brown bullheads collected...

  10. Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells

    OpenAIRE

    Maria Giuseppina Onesti; Paolo Fioramonti; Sara Carella; Pasquale Fino; Cinzia Marchese; Nicolò Scuderi

    2016-01-01

    Background. Systemic sclerosis (SSc) is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia) and opening (microstomia). We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs) injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were...

  11. High-Fat Diet and Palmitate Alter the Rhythmic Secretion of Glucagon-Like Peptide-1 by the Rodent L-cell.

    Science.gov (United States)

    Gil-Lozano, Manuel; Wu, W Kelly; Martchenko, Alexandre; Brubaker, Patricia L

    2016-02-01

    Secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is rhythmically regulated by an independent molecular clock. However, the impact of factors known to affect the activity of similar cell-autonomous clocks, such as circulating glucocorticoids and high-fat feeding, on GLP-1 secretory patterns remains to be elucidated. Herein the role of the endogenous corticosterone rhythm on the pattern of GLP-1 and insulin nutrient-induced responses was examined in corticosterone pellet-implanted rats. Moreover, the impact of nutrient excess on the time-dependent secretion of both hormones was assessed in rats fed a high-fat, high-sucrose diet. Finally, the effects of the saturated fatty acid, palmitate, on the L-cell molecular clock and GLP-1 secretion were investigated in vitro using murine GLUTag L-cells. Diurnal variations in GLP-1 and insulin nutrient-induced responses were maintained in animals lacking an endogenous corticosterone rhythm, suggesting that glucocorticoids are not the predominant entrainment factor for L-cell rhythmic activity. In addition to hyperglycemia, hyperinsulinemia, insulin resistance, and disorganization of feeding behavior, high-fat high-sucrose-fed rats showed a total abrogation of the diurnal variation in GLP-1 and insulin nutrient-induced responses, with comparable levels of both hormones at the normal peak (5:00 pm) and trough (5:00 am) of their daily pattern. Finally, palmitate incubation induced profound derangements in the rhythmic expression of circadian oscillators in GLUTag L-cells and severely impaired the secretory activity of these cells. Collectively our findings demonstrate that obesogenic diets disrupt the rhythmic activity of the L-cell, partially through a direct effect of specific nutritional components. PMID:26646204

  12. Aqueous Extracts of the Marine Brown Alga Lobophora variegata Inhibit HIV-1 Infection at the Level of Virus Entry into Cells

    KAUST Repository

    Kremb, Stephan

    2014-08-21

    In recent years, marine algae have emerged as a rich and promising source of molecules with potent activities against various human pathogens. The widely distributed brown alga Lobophora variegata that is often associated with tropical coral reefs exerts strong antibacterial and antiprotozoal effects, but so far has not been associated with specific anti-viral activities. This study investigated potential HIV-1 inhibitory activity of L. variegata collected from different geographical regions, using a cell-based full replication HIV-1 reporter assay. Aqueous L. variegata extracts showed strong inhibitory effects on several HIV-1 strains, including drug-resistant and primary HIV-1 isolates, and protected even primary cells (PBMC) from HIV-1-infection. Anti-viral potency was related to ecological factors and showed clear differences depending on light exposition or epiphyte growth. Assays addressing early events of the HIV-1 replication cycle indicated that L. variegata extracts inhibited entry of HIV-1 into cells at a pre-fusion step possibly by impeding mobility of virus particles. Further characterization of the aqueous extract demonstrated that even high doses had only moderate effects on viability of cultured and primary cells (PBMCs). Imaging-based techniques revealed extract effects on the plasma membrane and actin filaments as well as induction of apoptosis at concentrations exceeding EC50 of anti-HIV-1 activity by more than 400 fold. In summary, we show for the first time that L. variegata extracts inhibit HIV-1 entry, thereby suggesting this alga as promising source for the development of novel HIV-1 inhibitors.

  13. Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.

    Directory of Open Access Journals (Sweden)

    David F Razidlo

    Full Text Available Histone deacetylase (Hdac3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health.

  14. A new glycotoxins inhibitor attenuates insulin resistance in liver and fat cells.

    Science.gov (United States)

    Afridi, Shabbir Khan; Aftab, Meha Fatima; Murtaza, Munazza; Ghaffar, Safina; Karim, Aneela; Mughal, Uzma Rasool; Khan, Khalid Mohammed; Waraich, Rizwana Sanaullah

    2016-08-01

    Glycotoxins/Advanced glycation end products (AGEs) have implications in development of diabetes and related diseases. In the present study we deciphered the mechanisms of action of URM-II-81, a new derivative of isatin, in alleviation of insulin resistance in human hepatocytes and murine adipocytes. URM-II-81 reduced AGEs formation and receptor for advanced glycation end products (RAGE) expression in both cell types. We also observed suppression of methylglyoxal (MGO) mediated ROS production and deactivation of PKC-α. URM-II-81 restored proximal insulin signaling by modulating IRS-1 phosphorylation. URM-II-81 also alleviated MGO mediated diminished distal insulin signaling by increasing protein kinase B (PKB) and glycogen synthase kinase 3-beta (GSK-3-beta) phosphorylation. Glycogen synthesis was also increased in hepatocytes after treatment with URM-II-81. In adipocytes URM-II-81 prevented MGO induced reduced glucose uptake. We conclude that URM-II-81 can be a possible treatment target to address glycotoxins induced insulin resistance. PMID:27233608

  15. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

    Science.gov (United States)

    Aravena, Javier; Cabrera, Daniel; Simon, Felipe; Ezquer, Fernando

    2016-01-01

    Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs) are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes. PMID:27579157

  16. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

    Directory of Open Access Journals (Sweden)

    Johanna Abrigo

    2016-01-01

    Full Text Available Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes.

  17. Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.

    Directory of Open Access Journals (Sweden)

    Sara Becerril

    Full Text Available BACKGROUND: Leptin and nitric oxide (NO on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact of the absence of the inducible NO synthase (iNOS gene in the regulation of energy balance in ob/ob mice. METHODS AND FINDINGS: Double knockout (DBKO mice simultaneously lacking the ob and iNOS genes were generated, and the expression of molecules involved in the control of brown fat cell function was analyzed by real-time PCR, western-blot and immunohistochemistry. Twelve week-old DBKO mice exhibited reduced body weight (p<0.05, decreased amounts of total fat pads (p<0.05, lower food efficiency rates (p<0.05 and higher rectal temperature (p<0.05 than ob/ob mice. Ablation of iNOS also improved the carbohydrate and lipid metabolism of ob/ob mice. DBKO showed a marked reduction in the size of brown adipocytes compared to ob/ob mutants. In this sense, in comparison to ob/ob mice, DBKO rodents showed an increase in the expression of PR domain containing 16 (Prdm16, a transcriptional regulator of brown adipogenesis. Moreover, iNOS deletion enhanced the expression of mitochondria-related proteins, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1alpha, sirtuin-1 (Sirt-1 and sirtuin-3 (Sirt-3. Accordingly, mitochondrial uncoupling proteins 1 and 3 (Ucp-1 and Ucp-3 were upregulated in brown adipose tissue (BAT of DBKO mice as compared to ob/ob rodents. CONCLUSION: Ablation of iNOS improved the energy balance of ob/ob mice by decreasing food efficiency through an increase in thermogenesis. These effects may be mediated, in part, through the recovery of the BAT phenotype and brown fat cell function improvement.

  18. Cellular origins of cold-induced brown adipocytes in adult mice

    OpenAIRE

    Lee, Yun-Hee; Petkova, Anelia P.; Konkar, Anish A.; Granneman, James G.

    2014-01-01

    This work investigated how cold stress induces the appearance of brown adipocytes (BAs) in brown and white adipose tissues (WATs) of adult mice. In interscapular brown adipose tissue (iBAT), cold exposure increased proliferation of endothelial cells and interstitial cells expressing platelet-derived growth factor receptor, α polypeptide (PDGFRα) by 3- to 4-fold. Surprisingly, brown adipogenesis and angiogenesis were largely restricted to the dorsal edge of iBAT. Although cold stress did not i...

  19. Fat products

    OpenAIRE

    Alexandrov, Alexei

    2006-01-01

    The economics literature generally considers products as points in some characteristics space. Starting with Hotelling, this served as a convenient assumption, yet with more products being flexible or self-customizable to some degree it makes sense to think that products have positive measure. I develop a model where ?rms can o¤er interval long 'fat' products in the spatial model of differentiation. Contrary to the standard results pro?ts of the firms can decrease with increased differentiati...

  20. Impaired adipogenesis and insulin resistance in epicardial fat-mesenchymal cells from patients with cardiovascular disease.

    Science.gov (United States)

    Fernández-Trasancos, Angel; Fandiño-Vaquero, Rubén; Agra, Rosa María; Fernández, Angel Luis; Viñuela, Juan E; González-Juanatey, José Ramón; Eiras, Sonia

    2014-11-01

    The thickness of epicardial adipose tissue (EAT), which is an inflammatory source for coronary artery disease (CAD), correlates with insulin resistance. One trigger factor is impaired adipogenesis. Here, our aim was to clarify the underlying mechanisms of insulin resistance on EAT-mesenchymal cells (MC). EAT and subcutaneous adipose tissue (SAT) were collected from 19 patients who were undergoing heart surgery. Their dedifferentiated adipocytes (DAs) and/or MCs were cultured. After the induction of adipogenesis or stimulation with insulin, the expression of adipokines was analyzed using real-time polymerase chain reaction (PCR). Colorimetric assays were performed to measure glucose levels and proliferation rate. Proteins modifications were detected via the proteomic approach and Western blot. Our results showed lower adipogenic ability in EAT-MCs than in SAT-MCs. Maximum adiponectin levels were reached within 28-35 days of exposure to adipogenic inducers. Moreover, the adipogenesis profile in EAT-MCs was dependent on the patients' clinical characteristics. The low adipogenic ability of EAT-MCs might be associated with an insulin-resistant state because chronic insulin treatment reduced the inflammatory cytokine expression levels, improved the glucose consumption, and increased the post-translational modifications (PTMs) of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1). We found lower adipogenic ability in EAT-MCs than in SAT-MCs. This lower ability level was dependent on gender and the presence of diabetes, obesity, and CAD. Low adipogenesis ability and insulin resistance in EAT-MCs might shed light on the association between EAT dysfunction and cardiovascular disease. PMID:24648294

  1. Adipogenesis: new insights into brown adipose tissue differentiation.

    Science.gov (United States)

    Carobbio, Stefania; Rosen, Barry; Vidal-Puig, Antonio

    2013-12-01

    Confirmation of the presence of functional brown adipose tissue (BAT) in humans has renewed interest in investigating the potential therapeutic use of this tissue. The finding that its activity positively correlates with decreased BMI, decreased fat content, and augmented energy expenditure suggests that increasing BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy to prevent or treat obesity and its associated morbidities. The challenge now is to find a safe and efficient way to develop this idea. Whereas BAT has being widely studied in murine models both in vivo and in vitro, there is an urgent need for human cellular models to investigate BAT physiology and functionality from a molecular point of view. In this review, we focus on the latest insights surrounding BAT development and activation in rodents and humans. Then, we discuss how the availability of murine models has been essential to identify BAT progenitors and trace their lineage. Finally, we address how this information can be exploited to develop human cellular models for BAT differentiation/activation. In this context, human embryonic stem and induced pluripotent stem cells-based cellular models represent a resource of great potential value, as they can provide a virtually inexhaustible supply of starting material for functional genetic studies, -omics based analysis and validation of therapeutic approaches. Moreover, these cells can be readily genetically engineered, opening the possibility of generating patient-specific cellular models, allowing the investigation of the influence of different genetic backgrounds on BAT differentiation in pathological or in physiological states.

  2. Evidence for two types of brown adipose tissue in humans.

    Science.gov (United States)

    Lidell, Martin E; Betz, Matthias J; Dahlqvist Leinhard, Olof; Heglind, Mikael; Elander, Louise; Slawik, Marc; Mussack, Thomas; Nilsson, Daniel; Romu, Thobias; Nuutila, Pirjo; Virtanen, Kirsi A; Beuschlein, Felix; Persson, Anders; Borga, Magnus; Enerbäck, Sven

    2013-05-01

    The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was commonly believed to be the equivalent of the interscapular thermogenic organ of small mammals. This view was recently disputed on the basis of the demonstration that this depot consists of beige (also called brite) brown adipocytes, a newly identified type of brown adipocyte that is distinct from the classical brown adipocytes that make up the interscapular thermogenic organs of other mammals. A combination of high-resolution imaging techniques and histological and biochemical analyses showed evidence for an anatomically distinguishable interscapular BAT (iBAT) depot in human infants that consists of classical brown adipocytes, a cell type that has so far not been shown to exist in humans. On the basis of these findings, we conclude that infants, similarly to rodents, have the bona fide iBAT thermogenic organ consisting of classical brown adipocytes that is essential for the survival of small mammals in a cold environment.

  3. The production of sulfonated chitosan-sodium alginate found in brown algae (Sargassum sp.) composite membrane as proton exchange membrane fuel cell (PEMFC)

    Science.gov (United States)

    Wafiroh, Siti; Pudjiastuti, Pratiwi; Sari, Ilma Indana

    2016-03-01

    The majority of energy was used in this period is from fossil fuel, which getting decreased in the future. The objective of this research is production and characterization of sulfonated chitosan-sodium alginate found in brown algae (Sargassum sp.) composite membrane as Proton Exchange Membrane Fuel Cell (PEMFC) for alternative energy. PEMFC was produced with 4 variations (w/w) ratio between chitosan and sodium alginate, 8 : 0, 8 : 1, 8 : 2, 8 : 4 (w/w). The production of membrane was mixed sodium alginate solution into chitosan solution and sulfonated with H2SO4 0.72 N. The characterization of the PEM was uses Modulus Young analysis, water swelling, ion exchange capacity, FTIR, SEM, DTA, methanol permeability and proton conductivity. The result of the research, showed that the optimum membrane was with ratio 8 : 2 (w/w) that the Modulus Young 8564 kN/m2, water swelling 31.86%, ion exchange capacity 1.020 meq/g, proton conductivity 8,8 × 10-6 S/cm, methanol permeability 1.90 × 10-8 g/cm2s and glass transition temperature (Tg) 100.9 °C, crystalline temperature (Tc) 227.6 °C, and the melting temperature (Tm) 267.9 °C.

  4. Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Patricia Rivera

    Full Text Available Soy extracts have been claimed to be neuroprotective against brain insults, an effect related to the estrogenic properties of isoflavones. However, the effects of individual isoflavones on obesity-induced disruption of adult neurogenesis have not yet been analyzed. In the present study we explore the effects of pharmacological administration of daidzein, a main soy isoflavone, in cell proliferation, cell apoptosis and gliosis in the adult hippocampus of animals exposed to a very high-fat diet. Rats made obese after 12-week exposure to a standard or high-fat (HFD, 60% diets were treated with daidzein (50 mg kg(-1 for 13 days. Then, plasma levels of metabolites and metabolic hormones, cell proliferation in the subgranular zone of the dentate gyrus (SGZ, and immunohistochemical markers of hippocampal cell apoptosis (caspase-3, gliosis (GFAP and Iba-1, food reward factor FosB and estrogen receptor alpha (ERα were analyzed. Treatment with daidzein reduced food/caloric intake and body weight gain in obese rats. This was associated with glucose tolerance, low levels of HDL-cholesterol, insulin, adiponectin and testosterone, and high levels of leptin and 17β-estradiol. Daidzein increased the number of phospho-histone H3 and 5-bromo-2-deoxyuridine (BrdU-ir cells detected in the SGZ of standard diet and HFD-fed rats. Daidzein reversed the HFD-associated enhanced immunohistochemical expression of caspase-3, FosB, GFAP, Iba-1 and ERα in the hippocampus, being more prominent in the dentate gyrus. These results suggest that pharmacological treatment with isoflavones regulates metabolic alterations associated with enhancement of cell proliferation and reduction of apoptosis and gliosis in response to high-fat diet.

  5. Natural food science based novel approach toward prevention and treatment of obesity and type 2 diabetes: recent studies on brown rice and γ-oryzanol.

    Science.gov (United States)

    Kozuka, Chisayo; Yabiku, Kouichi; Takayama, Chitoshi; Matsushita, Masayuki; Shimabukuro, Michio

    2013-01-01

    The prevalences of obesity and type 2 diabetes mellitus are dramatically increasing, and there is a strong need for more effective and safer therapies. However, some of drugs show limited efficacy and considerable adverse effects. Furthermore, artificial energy-dense foods and non-caloric foods may promote overeating and weight gain. In this context, a natural food-based approach may represent a valuable means of tackling the obesity-diabetes syndrome. Although recent studies have shown that brown rice improves glucose intolerance and prevents obesity and type 2 diabetes in humans, the underlying molecular mechanisms remain unclear. We found that one of the major components of brown rice, γ-oryzanol (Orz), plays an important role in the metabolically beneficial effects of brown rice. Orz acts as a chemical chaperone and decreases high fat diet (HFD)-induced endoplasmic reticulum (ER) stress in the hypothalamus, thereby leading to a significant shift in preference from fatty to healthy foods. Orz also decreases HFD-induced ER stress in pancreatic β-cells and improves β-cell function. Notably, Orz directly acts on pancreatic islets and enhances glucose-stimulated insulin secretion (GSIS). This evidence highlights food preference as a promising therapeutic target in obesity-diabetes syndrome and suggests that brown rice and Orz may have potential for the treatment of obesity and type 2 diabetes in humans.

  6. Modulation of membrane phospholipids, the cytosolic calcium influx and cell proliferation following treatment of B16-F10 cells with recombinant phospholipase-D from Loxosceles intermedia (brown spider) venom.

    Science.gov (United States)

    Wille, Ana Carolina Martins; Chaves-Moreira, Daniele; Trevisan-Silva, Dilza; Magnoni, Mariana Gabriel; Boia-Ferreira, Marianna; Gremski, Luiza Helena; Gremski, Waldemiro; Chaim, Olga Meiri; Senff-Ribeiro, Andrea; Veiga, Silvio Sanches

    2013-06-01

    The mechanism through which brown spiders (Loxosceles genus) cause dermonecrosis, dysregulated inflammatory responses, hemolysis and platelet aggregation, which are effects reported following spider bites, is currently attributed to the presence of phospholipase-D in the venom. In the present investigation, through two-dimensional immunoblotting, we observed immunological cross-reactivity for at least 25 spots in crude Loxosceles intermedia venom, indicating high expression levels for different isoforms of phospholipase-D. Using a recombinant phospholipase-D from the venom gland of L. intermedia (LiRecDT1) in phospholipid-degrading kinetic experiments, we determined that this phospholipase-D mainly hydrolyzes synthetic sphingomyelin in a time-dependent manner, generating ceramide 1-phosphate plus choline, as well as lysophosphatidylcholine, generating lysophosphatidic acid plus choline, but exhibits little activity against phosphatidylcholine. Through immunofluorescence assays with antibodies against LiRecDT1 and using a recombinant GFP-LiRecDT1 fusion protein, we observed direct binding of LiRecDT1 to the membrane of B16-F10 cells. We determined that LiRecDT1 hydrolyzes phospholipids in detergent extracts and from ghosts of B16-F10 cells, generating choline, indicating that the enzyme can access and modulate and has activity against membrane phospholipids. Additionally, using Fluo-4, a calcium-sensitive fluorophore, it was shown that treatment of cells with phospholipase-D induced an increase in the calcium concentration in the cytoplasm, but without altering viability or causing damage to cells. Finally, based on the known endogenous activity of phospholipase-D as an inducer of cell proliferation and the fact that LiRecDT1 binds to the cell surface, hydrolyzing phospholipids to generate bioactive lipids, we employed LiRecDT1 as an exogenous source of phospholipase-D in B16-F10 cells. Treatment of the cells was effective in increasing their proliferation in a

  7. Effect of Oxytocin Administration before Milking on Milk Production, Somatic Cells Count and fat Contents in Milk of Nili-Ravi Buffaloes

    Directory of Open Access Journals (Sweden)

    Muhammad Saleem Akhtar*, Laeeq Akbar Lodhi1, Abdul Asim Farooq, M. Mazhar Ayaz, Maqbool Hussain, Mushtaq Hussain Lashari and Zafar Iqbal Chaudhary

    2012-06-01

    Full Text Available This study was escorted to know the effect of oxytocin administration before milking on milk production, somatic cells count and fat contents in milk of buffaloes. Twenty lactating Nili-Ravi buffaloes were randomly divided into two groups. Group A (n = 10 buffaloes were treated intramuscularly with 30 IU of oxytocin daily before the start of milking for the period of 7 days, whereas group B (n = 10 buffaloes were given no treatment and served as control. Milk samples were collected from all buffaloes 7 days before (Phase I, during (Phase II and after (Phase III the treatment. There were significantly higher (P<0.05 milk production (liters during phase-II in group A (8.57±0.07 liters buffaloes as compare to group B (8.40±0.04 liters whereas non-significant differences were recorded in the mean milk production between group A and B during phase-I (8.46 vs 8.43 liters and III (8.54 liters. Somatic cells count varied from 72.96 to 97.01 × 103 and 71.86 to 77.14 × 103 cells per ml in group A and B, respectively. Mean somatic cells count were significantly higher (P<0.05 in group A as compared to group B during phases II of study. During phase I, II and III, there were non-significant differences in fat percentage between two groups of buffaloes. It was concluded that milk production and somatic cells count in milk of Nili-Ravi buffalo were affected by oxytocin injection before milking whereas there was no effect of oxytocin on milk fat percentage.

  8. Protective effect of Spirulina platensis against cell damage and apoptosis in hepatic tissue caused by high fat diet.

    Science.gov (United States)

    Yigit, F; Gurel-Gurevin, E; Isbilen-Basok, B; Esener, O B B; Bilal, T; Keser, O; Altiner, A; Yilmazer, N; Ikitimur-Armutak, E I

    2016-01-01

    Spirulina platensis is a microalga that may be a source of antioxidants that can reduce body fat deposition. Consumption of a high fat diet produces elevated blood lipid levels, inflammation and apoptosis. We investigated the possible effects of S. platensis on the blood lipid profile, and liver inflammation and apoptosis in rats fed a high fat diet. Sixty-four young male rats were divided into eight equal groups. The control group was fed a basic diet. The experimental groups were fed a diet for 60 days that was prepared by mixing variable amounts of 43% vegetable oil and 10% cholesterol with or without 3% S. platensis mixed with the basal diet. Blood and liver tissue samples were collected from each animal. Serum samples were used to analyze lipid parameters, total antioxidant status and total oxidant status. iNOS and eNOS were determined by immunohistochemistry. TUNEL staining was used to detect apoptosis to investigate a possible connection between inflammation and apoptosis in the liver tissue. The relations between fat deposition and liver degeneration were assessed by Sirius red staining and alpha-smooth muscle actin immunostaining. S. platensis reduced serum HDL-C, LDL-C and triglyceride, increased HDL-C levels in rats fed a high fat diet to near control levels, and reduced iNOS levels and increased eNOS levels in the liver tissue compared to vegetable oil and cholesterol treated groups. The apoptotic index was reduced in the groups that were fed a high fat or a basic diet when supplemented with S. platensis. PMID:26820259

  9. Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells from cartilage, fat, and bone marrow in an ovine model of osteochondral focal defect.

    Science.gov (United States)

    Caminal, M; Peris, D; Fonseca, C; Barrachina, J; Codina, D; Rabanal, R M; Moll, X; Morist, A; García, F; Cairó, J J; Gòdia, F; Pla, A; Vives, J

    2016-08-01

    Current developments in tissue engineering strategies for articular cartilage regeneration focus on the design of supportive three-dimensional scaffolds and their use in combination with cells from different sources. The challenge of translating initial successes in small laboratory animals into the clinics involves pilot studies in large animal models, where safety and efficacy should be investigated during prolonged follow-up periods. Here we present, in a single study, the long-term (up to 1 year) effect of biocompatible porous scaffolds non-seeded and seeded with fresh ex vivo expanded autologous progenitor cells that were derived from three different cell sources [cartilage, fat and bone marrow (BM)] in order to evaluate their advantages as cartilage resurfacing agents. An ovine model of critical size osteochondral focal defect was used and the test items were implanted arthroscopically into the knees. Evidence of regeneration of hyaline quality tissue was observed at 6 and 12 months post-treatment with variable success depending on the cell source. Cartilage and BM-derived mesenchymal stromal cells (MSC), but not those derived from fat, resulted in the best quality of new cartilage, as judged qualitatively by magnetic resonance imaging and macroscopic assessment, and by histological quantitative scores. Given the limitations in sourcing cartilage tissue and the risk of donor site morbidity, BM emerges as a preferential source of MSC for novel cartilage resurfacing therapies of osteochondral defects using copolymeric poly-D,L-lactide-co-glycolide scaffolds. PMID:25595211

  10. Effect of Instant Cooked Giant Embryonic Rice on Body Fat Weight and Plasma Lipid Profile in High Fat-Fed Mice

    OpenAIRE

    Soo Im Chung; Tae Hyeong Kim; Rico, Catherine W.; Mi Young Kang

    2014-01-01

    The comparative effects of instant cooked rice made from giant embryo mutant or ordinary normal rice on body weight and lipid profile in high fat-fed mice were investigated. The animals were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal white (HF-NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat, plasma and hepatic tri...

  11. Effect of the ratios of unsaturated fatty acids on the expressions of genes related to fat and protein in the bovine mammary epithelial cells.

    Science.gov (United States)

    Sheng, R; Yan, S M; Qi, L Z; Zhao, Y L

    2015-04-01

    The objective of this study was to evaluate the effects of the different ratios of unsaturated fatty acids (UFAs) (oleic acid, linoleic acid, and linolenic acid) on the cell viability and triacylglycerol (TAG) content, as well as the mRNA expression of the genes related to lipid and protein synthesis in bovine mammary epithelial cells (BMECs). Primary cells were isolated from the mammary glands of Holstein dairy cows and were passaged twice. Afterward, the cells were randomly allocated to six treatments, five UFA-treated groups, and one control group. For all of the treatments, the the fetal bovine serum in the culture solution was replaced with fatty acid-free BSA (1 g/L), and the cells were treated with different ratios of oleic, linoleic, and linolenic acids (0.75:4:1, 1.5:10:1, 2:13.3:1, 3:20:1, and 4:26.7:1) for 48 h, which were group 1 to group 5. The control culture solution contained only fatty acid-free BSA without UFAs (0 μM). The results indicated that the cell viability was not affected by adding different ratios of UFAs, but the accumulation of TAG was significantly influenced by supplementing with different ratios of UFAs. Adding different ratios of UFAs suppressed the expression of ACACA and FASN but had the opposite effect on the abundances of FABP3 and CD36 mRNA. The expression levels of PPARG, SPEBF1, CSN1S1, and CSN3 mRNA in the BMECs were affected significantly after adding different ratios of UFAs. Our results suggested that groups 1, 2, and 3 (0.75:4:1, 1.5:10:1, and 2:13.3:1) had stronger auxo-action on fat synthesis in the BMECs, where group 3 (2:13.3:1) was the best, followed by group 4 (3:20:1). However, group 5 (4:26.7:1) was the worst. Genes related to protein synthesis in the BMECs were better promoted in groups 2 and 3, and group 3 had the strongest auxo-action, whereas the present study only partly examined the regulation of protein synthesis at the transcriptional level; more studies on translation level are needed in the future

  12. Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome.

    Science.gov (United States)

    Van De Pette, Matthew; Tunster, Simon J; McNamara, Grainne I; Shelkovnikova, Tatyana; Millership, Steven; Benson, Lindsay; Peirson, Stuart; Christian, Mark; Vidal-Puig, Antonio; John, Rosalind M

    2016-03-01

    The accurate diagnosis and clinical management of the growth restriction disorder Silver Russell Syndrome (SRS) has confounded researchers and clinicians for many years due to the myriad of genetic and epigenetic alterations reported in these patients and the lack of suitable animal models to test the contribution of specific gene alterations. Some genetic alterations suggest a role for increased dosage of the imprinted CYCLIN DEPENDENT KINASE INHIBITOR 1C (CDKN1C) gene, often mutated in IMAGe Syndrome and Beckwith-Wiedemann Syndrome (BWS). Cdkn1c encodes a potent negative regulator of fetal growth that also regulates placental development, consistent with a proposed role for CDKN1C in these complex childhood growth disorders. Here, we report that a mouse modelling the rare microduplications present in some SRS patients exhibited phenotypes including low birth weight with relative head sparing, neonatal hypoglycemia, absence of catch-up growth and significantly reduced adiposity as adults, all defining features of SRS. Further investigation revealed the presence of substantially more brown adipose tissue in very young mice, of both the classical or canonical type exemplified by interscapular-type brown fat depot in mice (iBAT) and a second type of non-classic BAT that develops postnatally within white adipose tissue (WAT), genetically attributable to a double dose of Cdkn1c in vivo and ex-vivo. Conversely, loss-of-function of Cdkn1c resulted in the complete developmental failure of the brown adipocyte lineage with a loss of markers of both brown adipose fate and function. We further show that Cdkn1c is required for post-transcriptional accumulation of the brown fat determinant PR domain containing 16 (PRDM16) and that CDKN1C and PRDM16 co-localise to the nucleus of rare label-retaining cell within iBAT. This study reveals a key requirement for Cdkn1c in the early development of the brown adipose lineages. Importantly, active BAT consumes high amounts of energy to

  13. Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome.

    Science.gov (United States)

    Van De Pette, Matthew; Tunster, Simon J; McNamara, Grainne I; Shelkovnikova, Tatyana; Millership, Steven; Benson, Lindsay; Peirson, Stuart; Christian, Mark; Vidal-Puig, Antonio; John, Rosalind M

    2016-03-01

    The accurate diagnosis and clinical management of the growth restriction disorder Silver Russell Syndrome (SRS) has confounded researchers and clinicians for many years due to the myriad of genetic and epigenetic alterations reported in these patients and the lack of suitable animal models to test the contribution of specific gene alterations. Some genetic alterations suggest a role for increased dosage of the imprinted CYCLIN DEPENDENT KINASE INHIBITOR 1C (CDKN1C) gene, often mutated in IMAGe Syndrome and Beckwith-Wiedemann Syndrome (BWS). Cdkn1c encodes a potent negative regulator of fetal growth that also regulates placental development, consistent with a proposed role for CDKN1C in these complex childhood growth disorders. Here, we report that a mouse modelling the rare microduplications present in some SRS patients exhibited phenotypes including low birth weight with relative head sparing, neonatal hypoglycemia, absence of catch-up growth and significantly reduced adiposity as adults, all defining features of SRS. Further investigation revealed the presence of substantially more brown adipose tissue in very young mice, of both the classical or canonical type exemplified by interscapular-type brown fat depot in mice (iBAT) and a second type of non-classic BAT that develops postnatally within white adipose tissue (WAT), genetically attributable to a double dose of Cdkn1c in vivo and ex-vivo. Conversely, loss-of-function of Cdkn1c resulted in the complete developmental failure of the brown adipocyte lineage with a loss of markers of both brown adipose fate and function. We further show that Cdkn1c is required for post-transcriptional accumulation of the brown fat determinant PR domain containing 16 (PRDM16) and that CDKN1C and PRDM16 co-localise to the nucleus of rare label-retaining cell within iBAT. This study reveals a key requirement for Cdkn1c in the early development of the brown adipose lineages. Importantly, active BAT consumes high amounts of energy to

  14. Irradiated brown dwarfs

    CERN Document Server

    Casewell, S L; Lawrie, K A; Maxted, P F L; Dobbie, P D; Napiwotzki, R

    2014-01-01

    We have observed the post common envelope binary WD0137-349 in the near infrared $J$, $H$ and $K$ bands and have determined that the photometry varies on the system period (116 min). The amplitude of the variability increases with increasing wavelength, indicating that the brown dwarf in the system is likely being irradiated by its 16500 K white dwarf companion. The effect of the (primarily) UV irradiation on the brown dwarf atmosphere is unknown, but it is possible that stratospheric hazes are formed. It is also possible that the brown dwarf (an L-T transition object) itself is variable due to patchy cloud cover. Both these scenarios are discussed, and suggestions for further study are made.

  15. Buddleja officinalis Maximowicz Extract Inhibits Lipid Accumulation on Adipocyte Differentiation in 3T3-L1 Cells and High-Fat Mice

    Directory of Open Access Journals (Sweden)

    Jin-Kyu Kim

    2012-07-01

    Full Text Available Obesity is a global health problem. It is also known to be a risk factor for the development of metabolic disorders, type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we elucidated that Buddleja officinalis Maximowicz extract significantly inhibited lipid accumulation during 3T3-L1 adipocyte differentiation. Furthermore, Buddleja officinalis Maximowicz extract reduced the body weight gain induced through feeding a high-fat diet to C57BL/6 mice. The treatment of Buddleja officinalis Maximowicz extract significantly reduced the adipose tissue weight to 2.7/100 g of body weight in high-fat mice. When their adipose tissue morphology was investigated for histochemical staining, the distribution of cell size in the high-fat diet groups was hypertrophied compared with those from Buddleja officinalis Maximowicz extract-treated mice. In addition, in Buddleja officinalis Maximowicz extract-treated mice, a significant reduction of serum triglyceride and T-cholesterol was observed at to 21% and 17%, respectively. The discovery of bioactive compounds from diet or dietary supplementation is one of possible ways to control obesity and to prevent or reduce the risks of various obesity-related diseases. These results support that Buddleja officinalis Maximowicz extract is expected to create the therapeutic interest with respect to the treatment of obesity.

  16. Brown adipose tissue and its therapeutic potential.

    Science.gov (United States)

    Lidell, M E; Betz, M J; Enerbäck, S

    2014-10-01

    Obesity and related diseases are a major cause of human morbidity and mortality and constitute a substantial economic burden for society. Effective treatment regimens are scarce, and new therapeutic targets are needed. Brown adipose tissue, an energy-expending tissue that produces heat, represents a potential therapeutic target. Its presence is associated with low body mass index, low total adipose tissue content and a lower risk of type 2 diabetes mellitus. Knowledge about the development and function of thermogenic adipocytes in brown adipose tissue has increased substantially in the last decade. Important transcriptional regulators have been identified, and hormones able to modulate the thermogenic capacity of the tissue have been recognized. Intriguingly, it is now clear that humans, like rodents, possess two types of thermogenic adipocytes: the classical brown adipocytes found in the interscapular brown adipose organ and the so-called beige adipocytes primarily found in subcutaneous white adipose tissue after adrenergic stimulation. The presence of two distinct types of energy-expending adipocytes in humans is conceptually important because these cells might be stimulated and recruited by different signals, raising the possibility that they might be separate potential targets for therapeutic intervention. In this review, we will discuss important features of the energy-expending brown adipose tissue and highlight those that may serve as potential targets for pharmacological intervention aimed at expanding the tissue and/or enhancing its function to counteract obesity.

  17. Deep Sequencing and Screening of Differentially Expressed MicroRNAs Related to Milk Fat Metabolism in Bovine Primary Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Binglei Shen

    2016-02-01

    Full Text Available Milk fat is a key factor affecting milk quality and is also a major trait targeted in dairy cow breeding. To determine how the synthesis and the metabolism of lipids in bovine milk is regulated at the miRNA level, primary mammary epithelial cells (pMEC derived from two Chinese Holstein dairy cows that produced extreme differences in milk fat percentage were cultured by the method of tissue nubbles culture. Small RNA libraries were constructed from each of the two pMEC groups, and Solexa sequencing and bioinformatics analysis were then used to determine the abundance of miRNAs and their differential expression pattern between pMECs. Target genes and functional prediction of differentially expressed miRNAs by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis illustrated their roles in milk fat metabolism. Results show that a total of 292 known miRNAs and 116 novel miRNAs were detected in both pMECs. Identification of known and novel miRNA candidates demonstrated the feasibility and sensitivity of sequencing at the cellular level. Additionally, 97 miRNAs were significantly differentially expressed between the pMECs. Finally, three miRNAs including bta-miR-33a, bta-miR-152 and bta-miR-224 whose predicted target genes were annotated to the pathway of lipid metabolism were screened and verified by real-time qPCR and Western-blotting experiments. This study is the first comparative profiling of the miRNA transcriptome in pMECs that produce different milk fat content.

  18. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes

    DEFF Research Database (Denmark)

    Petrovic, Natasa; Walden, Tomas B; Shabalina, Irina G;

    2009-01-01

    The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain...... physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes not only the expression of PGC-1alpha and mitochondriogenesis...... associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells...

  19. Saturated fat (image)

    Science.gov (United States)

    Saturated fat can raise blood cholesterol and can put you at risk for heart disease and stroke. You should ... limit any foods that are high in saturated fat. Sources of saturated fat include whole-milk dairy ...

  20. Browning of white adipose tissue: role of hypothalamic signaling.

    Science.gov (United States)

    Bi, Sheng; Li, Lin

    2013-10-01

    Two types of fat, white adipose tissue (WAT) and brown adipose tissue (BAT), exist in mammals including adult humans. While WAT stores excess calories and an excessive accumulation of fat causes obesity, BAT dissipates energy to produce heat through nonshivering thermogenesis for protection against cold environments and provides the potential for the development of novel anti-obesity treatments. The hypothalamus plays a central role in the control of energy balance. Specifically, recent observations indicate the importance of the dorsomedial hypothalamus (DMH) in thermoregulation. We have found that the orexigenic neuropeptide Y (NPY) in the DMH has distinct actions in modulating adiposity and BAT thermogenesis. Knockdown of NPY in the DMH elevates the thermogenic activity of classic BAT and promotes the development of brown adipocytes in WAT, leading to increased thermogenesis. These findings identify a novel potential target for combating obesity.

  1. A role of active brown adipose tissue in cancer cachexia?

    Directory of Open Access Journals (Sweden)

    Emiel Beijer

    2012-06-01

    Full Text Available Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT. Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

  2. Brown Swiss cattle cytogenetic analysis

    Directory of Open Access Journals (Sweden)

    Rita Maria Ladeira Pires

    2010-02-01

    Full Text Available At 1985, a Brown Swiss herd from the Institute of Animal Science and Pastures, APTA/ SAA was cytogenetically analyzed and 1/29 Robertsonian translocation was observed. Such anomaly is related to fertility reduction. Quimeric abnormality such as 60,XX/60,XY in freemartin females. This study aimed to evaluate the incidence of cromossomic abnormalities in Brown Swiss animals, descending form herd karyotyped earlier. After 25 years, 127 animals (97 females and 30 males from this herd were karyotyped by metaphases obtained from blood lymphocyte cultures. The typical diploid number 2n=60, 58 acrocentric and two X submetacentric chromosomes were confirmed in 94 females and in 27 males the sexual complement X and Y, both submetacentric, although from different sizes. Four females from gemelar parturition whit males were karyotyped. Three of them presented quimerism 60,XX/60,XY (one with 25.8% of female cells (XX and 74.2% male cells (XY; one another with 10% of cells XX e 90% of XY and the third with 50% of each type showing genital masculinization, diagnosed as freemartism and discarded from herd. Two hundred and five cells were analyzed from another female twins and only 60,XX cells were found, diagnosed as normal. His sister also were normal (60,XY. The another three males were also analyzed from gemelar heterosexual parturition, with karyotype 60,XX/60,XY. Cytogenetic analysis are a safe methodology for freemartin abnormalities identification in female bovine twins with male bovine, giving the opportunity of selecting fertile animals, avoiding loses in the management of sterile animals. Robertsonian’s translocation was not observed in any of the animals analyzed.

  3. Platlet Rich Plasma (PRP) Improves Fat Grafting Outcomes

    OpenAIRE

    Modarressi Ghavami, Seyed Ali

    2013-01-01

    Autologous fat transfer offers many qualities of a ideal soft tissue filler. Main advantages of fat grafting ensue from the fact that the lipoaspirate tissue is an abundant source of regenerative pluripotential cells. However, the reported rates of fat cell survival vary greatly in the medical literature (10-90%). Different techniques of harvesting, processing, and reinjecting the fat cells are so claimed to be responsible for these differences, without any agreement concerning the best way t...

  4. Fucoidans from brown seaweeds

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Meyer, Anne S.

    2013-01-01

    Fucoidan or fucoidans cover a family of sulfated fucose-rich polysaccharides, built of a backbone of L-fucose units, and characteristically found in brown seaweeds. Fucoidans have potential therapeutic properties, including anti-inflammatory and anti-coagulant activities, as well as anti...

  5. A New Role for Browning as a Redox and Stress Adaptive Mechanism?

    OpenAIRE

    Jeanson, Yannick; Carrière, Audrey; Casteilla, Louis

    2015-01-01

    The worldwide epidemic of obesity and metabolic disorders is focusing the attention of the scientific community on white adipose tissue (WAT) and its biology. This tissue is characterized not only by its capability to change in size and shape but also by its heterogeneity and versatility. WAT can be converted into brown fat-like tissue according to different physiological and pathophysiological situations. The expression of uncoupling protein-1 in brown-like adipocytes changes their function ...

  6. Regulation of brown adipocyte metabolism by myostatin/follistatin signaling

    Directory of Open Access Journals (Sweden)

    Rajan eSingh

    2014-10-01

    Full Text Available Obesity develops from perturbations of cellular bioenergetics, when energy uptake exceeds energy expenditure, and represents a major risk factor for the development of type 2 diabetes, dyslipidemia, cardiovascular disease, cancer, and other conditions. Brown adipose tissue (BAT has long been known to dissipate energy as heat and contribute to energy expenditure, but its presence and physiological role in adult human physiology has been questioned for years. Recent demonstrations of metabolically active brown fat depots in adult humans have revolutionized current therapeutic approaches for obesity-related diseases. The balance between white adipose tissue (WAT and BAT affects the systemic energy balance and is widely believed to be the key determinant in the development of obesity and related metabolic diseases. Members of the transforming growth factor-beta (TGF-β superfamily play an important role in regulating overall energy homeostasis by modulation of brown adipocyte characteristics. Inactivation of TGF-β/Smad3/myostatin (Mst signaling promotes browning of white adipocytes, increases mitochondrial biogenesis and protects mice from diet-induced obesity, suggesting the need for development of a novel class of TGF-β/Mst antagonists for the treatment of obesity and related metabolic diseases. We recently described an important role of follistatin (Fst, a soluble glycoprotein that is known to bind and antagonize Mst actions, during brown fat differentiation and the regulation of cellular metabolism. Here we highlight various investigations performed using different in vitro and in vivo models to support the contention that targeting TGF-β/Mst signaling enhances brown adipocyte functions and regulates energy balance, reducing insulin resistance and curbing the development of obesity and diabetes.

  7. Acute bone crises in sickle cell disease: the T1 fat-saturated sequence in differentiation of acute bone infarcts from acute osteomyelitis

    International Nuclear Information System (INIS)

    Aim: To prove the hypothesis that acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells (RBCs) in bone marrow, and to evaluate the unenhanced T1 fat-saturated (fs) sequence in the differentiation of acute bone infarction from acute osteomyelitis in patients with sickle-cell disease. Materials and methods: Two studies were undertaken: an experimental study using in-vitro packed red blood cells and normal volunteers, and a retrospective clinical study of 86 magnetic resonance imaging (MRI) studies. For the experimental study containers of packed RBCs were placed between the knees of four healthy volunteers with a saline bag under the containers as an additional control, and were scanned with the pre-contrast T1-fs sequence. Signal intensity (SI) ratios were obtained for packed RBCs:skeletal muscle and packed RBCs:saline. For the clinical study, the SIs of normal bone marrow, packed RBCs, bone and/or soft-tissue lesions, and normal skeletal muscle of 74 patients (86 MRI studies) were measured using unenhanced, T1 fat-saturated MRI. The ratios of the above SIs to normal skeletal muscle were calculated and subjected to statistical analysis. Results: Fifty-one of 86 MRI studies were included in the final analysis. The ratios of SIs for normal bone marrow, packed red cells, bone infarction, acute osteomyelitis, and soft-tissue lesions associated with bone infarct, compared with normal skeletal muscle were (mean ± SD) 0.9 ± 0.2, 2.1 ± 0.7, 1.7 ± 0.5, 1.0 ± 0.3, and 2.2 ± 0.7, respectively. The difference in the ratio of SIs of bone infarcts and osteomyelitis was significant (p = 0.003). The final diagnoses were bone infarction (n = 50), acute osteomyelitis (n = 1), and co-existent bone infarction and osteomyelitis (n = 2). Seven patients who had suspected osteomyelitis underwent image-guided aspiration. Conclusion: Acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells in the bone marrow. The

  8. Dietary lipids: less fat or best fat?

    OpenAIRE

    Chardigny Jean-Michel

    2013-01-01

    Obesity and overweight occurrence is growing around the word. This is often considered as a consequence of high fat diets, and some recommendations encourage ‘‘light’’ diets, including low fat intake. However, most trials with low fat intake do not demonstrate any benefit and could be worse than low carbohydrate diets. The key role of insulin could explain that eating fat do not make body fat. On the other hand, several unbalanced fatty acid intake are reported, i.e. saturated/mononunsaturate...

  9. Dietary lipids: less fat or best fat?

    Directory of Open Access Journals (Sweden)

    Chardigny Jean-Michel

    2013-03-01

    Full Text Available Obesity and overweight occurrence is growing around the word. This is often considered as a consequence of high fat diets, and some recommendations encourage ‘‘light’’ diets, including low fat intake. However, most trials with low fat intake do not demonstrate any benefit and could be worse than low carbohydrate diets. The key role of insulin could explain that eating fat do not make body fat. On the other hand, several unbalanced fatty acid intake are reported, i.e. saturated/mononunsaturated fatty acids and w6/w3 polyunsaturated fatty acids. Thus, fat intake could be improved in this respect. Moreover, the molecular and supramolecular structures of fat in food are new challenges to address in order to ameliorate the recommendations for healthy diets.

  10. The trochanteric fat pad

    Directory of Open Access Journals (Sweden)

    P. Panettiere

    2011-05-01

    Full Text Available Technological developments based on the use of autologous white adipose tissue (WAT attracted attention to minor fat depots as possible sources of adipose tissue. In plastic surgery, the trochanteric fatty pad is one of the most used WAT depots for its location and organoleptic characteristics that make it particularly suitable for reconstructive procedures. Despite its wide use in clinic, the structure of this depot has never been studied in detail and it is not known if structural differences exist among trochanteric fat and other subcutaneous WAT depots. The present study was performed on trochanteric fat pad with the aim to clarify the morphology of its adipocytes, stroma and microcirculation, with particular reference to the stem niches. Histological and ultrastructural studies showed that the main peculiar feature of the trochanteric fat concerns its stromal component, which appears less dense than in the other subcutaneous WATs studied. The intra-parenchymal collagen stroma is poor and the extracellular compartment shows large spaces, filled with electron-light material, in which isolated collagen bundles are present. The adipocytes are wrapped in weak and easily detachable collagen baskets. These connective sheaths are very thin compared to the sheaths in other subcutaneous WAT depots. The capillaries are covered by large, long and thin elements surrounded by an external lamina; these perivascular cells are poor in organelles and mainly contain poly-ribosomes. In conclusion, when compared to other WAT deposits, the trochanteric fatty pad shows structural peculiarities in its stroma and microcirculation suggesting a high regenerative potential. Resistance, dissociability, microvascular weft and high regenerative potential make the trochanteric fatty pad a privileged source for harvesting in autologous WAT-based regenerative procedures.

  11. Adverse Fat Depots and Marrow Adiposity Are Associated With Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Mostoufi-Moab, Sogol; Magland, Jeremy; Isaacoff, Elizabeth J; Sun, Wenli; Rajapakse, Chamith S; Zemel, Babette; Wehrli, Felix; Shekdar, Karuna; Baker, Joshua; Long, Jin; Leonard, Mary B

    2015-09-01

    Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12 to 25 years) a median of 9.7 (4.3 to 19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. AlloHSCT survivors had lower Leg-LM (p treatment-related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long-term survivors demonstrated sarcopenic obesity, insulin resistance, and vertebral deformities. Future studies are needed to identify strategies to prevent and treat metabolic and skeletal complications in this growing population of childhood alloHSCT survivors. PMID:25801428

  12. Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells

    Directory of Open Access Journals (Sweden)

    Maria Giuseppina Onesti

    2016-01-01

    Full Text Available Background. Systemic sclerosis (SSc is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia and opening (microstomia. We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were enrolled from the outpatient clinic of Plastic Surgery Department of Sapienza University of Rome. Patients were divided into two groups as follows: 5 patients were treated with fat transplantation and 5 patients received infiltration of ADSCs produced by cell factory of our institution. To value mouth opening, we use the Italian version of Mouth Handicap in Systemic Sclerosis Scale (IvMHISS. Mouth opening was assessed in centimetres (Maximal Mouth Opening, MMO. In order to evaluate compliance and physician and patient satisfaction, we employed a Questionnaire of Satisfaction and the Visual Analogic Scale (VAS performed before starting study and 1 year after the last treatment. Results and Conclusion. We noticed that both procedures obtained significant results but neither one emerged as a first-choice technique. The present clinical experimentation should be regarded as a starting point for further experimental research and clinical trials.

  13. Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells.

    Science.gov (United States)

    Onesti, Maria Giuseppina; Fioramonti, Paolo; Carella, Sara; Fino, Pasquale; Marchese, Cinzia; Scuderi, Nicolò

    2016-01-01

    Background. Systemic sclerosis (SSc) is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia) and opening (microstomia). We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs) injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were enrolled from the outpatient clinic of Plastic Surgery Department of Sapienza University of Rome. Patients were divided into two groups as follows: 5 patients were treated with fat transplantation and 5 patients received infiltration of ADSCs produced by cell factory of our institution. To value mouth opening, we use the Italian version of Mouth Handicap in Systemic Sclerosis Scale (IvMHISS). Mouth opening was assessed in centimetres (Maximal Mouth Opening, MMO). In order to evaluate compliance and physician and patient satisfaction, we employed a Questionnaire of Satisfaction and the Visual Analogic Scale (VAS) performed before starting study and 1 year after the last treatment. Results and Conclusion. We noticed that both procedures obtained significant results but neither one emerged as a first-choice technique. The present clinical experimentation should be regarded as a starting point for further experimental research and clinical trials. PMID:26880939

  14. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Yong Pil [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Department of Pharmaceutical Engineering, International University of Korea, Jinju (Korea, Republic of); Choi, Jae Ho; Kim, Hyung Gyun; Khanal, Tilak; Song, Gye Young [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Nam, Myoung Soo [College of Agriculture and Life Sciences, Chungnam National University, Daejeon (Korea, Republic of); Lee, Hyun-Sun [Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Chung, Young Chul; Lee, Young Chun [Division of Food Science, International University of Korea, Jinju (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2013-03-01

    AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and sterol regulatory element-binding protein-1c (SREBP-1c) pathway. Saponins, particularly platycodin D, from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have a variety of pharmacological properties, including antioxidant and hepatoprotective properties. The aim of this study was to investigate the effects of CKS on hepatic lipogenesis and on the expression of genes involved in lipogenesis, and the mechanisms involved. CKS attenuated fat accumulation and the induction of the lipogenic genes encoding SREBP-1c and fatty acid synthase in the livers of HFD-fed rats and in steatotic HepG2 cells. Blood biochemical analyses and histopathological examinations showed that CKS prevented liver injury. CKS and platycodin D each increased the phosphorylation of AMPK and acetyl-CoA carboxylase in HFD-fed rats and HepG2 cells. The use of specific inhibitors showed that platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells. This study demonstrates that CKS or platycodin D alone can regulate hepatic lipogenesis via an AMPK-dependent signalling pathway. - Highlights: ► CKS attenuated fat accumulation in HFD-fed rats and in steatotic HepG2 cells. ► CKS and its major component, platycodin D, inhibited the levels of SREBP-1 and FAS. ► CKS and platycodin D increased the phosphorylation of AMPK and ACC. ► Platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells.

  15. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells

    International Nuclear Information System (INIS)

    AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and sterol regulatory element-binding protein-1c (SREBP-1c) pathway. Saponins, particularly platycodin D, from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have a variety of pharmacological properties, including antioxidant and hepatoprotective properties. The aim of this study was to investigate the effects of CKS on hepatic lipogenesis and on the expression of genes involved in lipogenesis, and the mechanisms involved. CKS attenuated fat accumulation and the induction of the lipogenic genes encoding SREBP-1c and fatty acid synthase in the livers of HFD-fed rats and in steatotic HepG2 cells. Blood biochemical analyses and histopathological examinations showed that CKS prevented liver injury. CKS and platycodin D each increased the phosphorylation of AMPK and acetyl-CoA carboxylase in HFD-fed rats and HepG2 cells. The use of specific inhibitors showed that platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells. This study demonstrates that CKS or platycodin D alone can regulate hepatic lipogenesis via an AMPK-dependent signalling pathway. - Highlights: ► CKS attenuated fat accumulation in HFD-fed rats and in steatotic HepG2 cells. ► CKS and its major component, platycodin D, inhibited the levels of SREBP-1 and FAS. ► CKS and platycodin D increased the phosphorylation of AMPK and ACC. ► Platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells

  16. Construction of fat-1 adipose tissue specific expression vector and production of goat transgenic fibroblast cell line%fat-1基因脂肪组织特异性表达载体的构建及其山羊转基因细胞系的建立

    Institute of Scientific and Technical Information of China (English)

    陈建文; 刘星; 桂涛; 李运生; 章孝荣; 张瑾; 张运海

    2012-01-01

    The aim of this study is to construct a marker removable, fat-1 adipose tissue specific expression vector and produce the transgenic goat fibroblast cell line for nuclear transfer. Firstly, the fat-1 gene was syn-thezised and a fat-1 adipose tissue specific expression vector was constructed. Secondly, the adipose tissue specific expression cassette was subcloned into a marker removable backbone vector (MCS-3s-LoxP-RFP) to construct a fat-1 marker removable adipose tissue specific expression vector driven by mouse Fabp4 promoter. Fi-nally, the goat fetal fibroblasts was transfected with the vector by Lipofectmine 2000 and selected in medium with G418 for two weeks, and then G418 resistant transfectants were identified by PCR. The results showed that the fat-1 marker removable adipose tissue specific expression vector was successfully constructed and the transgenic goat fibroblast cell lines were well established. It would pave the way for obtaining the marker-free fat-1 transgenic goat by SCNT.%旨在构建一种筛选标记可全部去除的脂肪组织特异性表达fat-1基因的载体,将其转染山羊胎儿成纤维细胞,筛选出稳定整合fat-1基因的转基因细胞系.首先将人工合成的fat-1基因连接至L28-Wnt10b载体(1种带有小鼠脂肪组织特异性启动子Fabp4的载体)上,构建成fat-1基因脂肪组织特异性表达载体L28-fat1;同时经多次克隆构建成1种筛选标记可全部去除的骨架载体MCS-3s-LoxP-RFP;然后,利用Hind Ⅲ和Not 1对上述2种载体进行双酶切,接着进行连接,构建出筛选标记可全部去除的脂肪组织特异性表达fat-1基因的表达载体.采用脂质体介导的方法转染山羊胎儿成纤维细胞,通过G418筛选转基因细胞.酶切鉴定及PCR检测结果表明,成功构建了3s-LoxP-RFP-FABP4-fat1表达载体,并首次获得了脂肪组织特异性表达fat-1基因的山羊胎儿成纤维转基因细胞系,为将来通过体细胞核移植创制脂肪组织特异表达fat

  17. Inhibitory effect of fat-1 gene on the proliferation of colon cancer cell HT-29%fat-1基因对结肠癌HT-29细胞增殖的抑制作用

    Institute of Scientific and Technical Information of China (English)

    刘晓蕾; 葛银林; 蒋正尧

    2007-01-01

    目的 探讨fat-1基因在结肠癌HT-29细胞凋亡、增殖以及细胞周期中所起的作用.方法 构建真核表达载体(pEGFP -fat-1),用脂质体介导的方法转染到结肠癌HT-29细胞,通过荧光显微镜观察及RT-PCR检测fat-1基因的表达,气相色谱分析检测fat-1基因对HT-29细胞n-6/n-3多聚不饱和脂肪酸(PUFAs)比例的影响,MTT法分析fat-1基因对HT-29细胞增殖的影响,流式细胞术检测fat-1基因对HT-29细胞凋亡和细胞周期的影响.结果 成功构建了真核表达载体pEGFP -fat-1,并在HT-29细胞内有效表达.fat-1基因通过降低HT-29细胞内n-6/n-3 PUFAs的比例抑制HT-29细胞的增殖,促进其凋亡,细胞增殖主要被阻滞在S期.结论 fat-1基因改变HT-29细胞n-6/n-3 PUFAs比例后,通过一定的信号转导途径促进大部分HT-29细胞在S期凋亡,抑制了其增殖.

  18. Emulsion Mapping in Pork Meat Emulsion Systems with Various Lipid Types and Brown Rice Fiber.

    Science.gov (United States)

    Choi, Yun-Sang; Kim, Young-Boong; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Jeong, Tae-Jun; Park, Jinhee; Kim, Cheon-Jei

    2015-01-01

    This study was conducted to evaluate emulsion mapping between emulsion stability and cooking yields, apparent viscosity, and hardness of reduced-fat pork emulsion systems. The reduced-fat emulsion systems were supplemented with different lipid types and brown rice bran fiber (BRF) concentrations. Compared to the control with 30% back fat, lower emulsion stability and higher cooking yield of meat emulsion systems were observed in T1 (30% back fat+1% BRF), T2 (30% back fat+2% BRF), T3 (30% back fat+3% BRF), T4 (30% back fat+6% BRF), and T15 (10% back fat+10% canola oil+2% BRF). Lower emulsion stability and higher apparent viscosity were observed in T1, T2, T3, T4, and T8 (20% back fat+3% BRF) compared to the control. Lower emulsion stability and higher hardness was detected in all treatments compared with the control, except T5 (20% back fat), T10 (10% back fat+10% canola oil+2% BRF), T11 (10% back fat+10% olive oil+2% BRF), T12 (10% back fat+10% grape seed oil+2% BRF), and T13 (10% back fat+10% soybean oil+2% BRF). This approach has been found particularly useful for highlighting differences among the emulsified properties in emulsion meat products. Thus, the results obtained with emulsion mapping are useful in making emulsified meat products of desired quality characteristics, partially replacing pork back fat with a mix of 10% back fat, 10% canola oil and 2% BRF was most similar to the control with 30% pork back fat. PMID:26761836

  19. Insulin resistance and beta-cell function in different ethnic groups in Kenya: the role of abdominal fat distribution

    DEFF Research Database (Denmark)

    Christensen, D.L.; Faurholt-Jepsen, D.; Faerch, K.;

    2014-01-01

    = 378), and Maasai (n = 348) was conducted. All participants had a standard 75-g oral glucose tolerance test (OGTT). Venous blood samples were collected at 0, 30, and 120 min. Serum insulin was analysed at 0 and 30 min. From the OGTT, we assessed the homoeostasis model assessment of insulin resistance...... compared to the Luo and Kamba, respectively. Adjustments of SAT (range 0.1–7.1 cm) and VAT (range 1.5–14.2 cm) largely explained these inter-group differences with the Maasai having the highest combined abdominal fat accumulation. The Maasai had the highest insulin resistance and secretion, but the lowest...

  20. Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

    OpenAIRE

    Grefhorst, Aldo; van den Beukel, Johanna C; van Houten, E Leonie AF; Steenbergen, Jacobie; Visser, Jenny A.; Themmen, Axel PN

    2015-01-01

    Background In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed in BAT and are involved in BAT activity. We hypothesized that differential expression of BMPs and FGFs might contribute to sex differences in BAT activity. Methods We investigated the expression of BMPs and FG...

  1. Test-day somatic cell score, fat-to-protein ratio and milk yield as indicator traits for sub-clinical mastitis in dairy cattle.

    Science.gov (United States)

    Jamrozik, J; Schaeffer, L R

    2012-02-01

    Test-day (TD) records of milk, fat-to-protein ratio (F:P) and somatic cell score (SCS) of first-lactation Canadian Holstein cows were analysed by a three-trait finite mixture random regression model, with the purpose of revealing hidden structures in the data owing to putative, sub-clinical mastitis. Different distributions of the data were allowed in 30 intervals of days in milk (DIM), covering the lactation from 5 to 305 days. Bayesian analysis with Gibbs sampling was used for model inferences. Estimated proportion of TD records originated from cows infected with mastitis was 0.66 in DIM from 5 to 15 and averaged 0.2 in the remaining part of lactation. Data from healthy and mastitic cows exhibited markedly different distributions, with respect to both average value and the variance, across all parts of lactation. Heterogeneity of distributions for infected cows was also apparent in different DIM intervals. Cows with mastitis were characterized by smaller milk yield (down to -5 kg) and larger F:P (up to 0.13) and SCS (up to 1.3) compared with healthy contemporaries. Differences in averages between healthy and infected cows for F:P were the most profound at the beginning of lactation, when a dairy cow suffers the strongest energy deficit and is therefore more prone to mammary infection. Residual variances for data from infected cows were substantially larger than for the other mixture components. Fat-to-protein ratio had a significant genetic component, with estimates of heritability that were larger or comparable with milk yield, and was not strongly correlated with milk and SCS on both genetic and environmental scales. Daily milk, F:P and SCS are easily available from milk-recording data for most breeding schemes in dairy cattle. Fat-to-protein ratio can potentially be a valuable addition to SCS and milk yield as an indicator trait for selection against mastitis.

  2. Rorα deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue.

    Science.gov (United States)

    Lau, Patrick; Tuong, Zewen K; Wang, Shu-Ching; Fitzsimmons, Rebecca L; Goode, Joel M; Thomas, Gethin P; Cowin, Gary J; Pearen, Michael A; Mardon, Karine; Stow, Jennifer L; Muscat, George E O

    2015-01-15

    The Rar-related orphan receptor-α (Rorα) is a nuclear receptor that regulates adiposity and is a potential regulator of energy homeostasis. We have demonstrated that the Rorα-deficient staggerer (sg/sg) mice display a lean and obesity-resistant phenotype. Adaptive Ucp1-dependent thermogenesis in beige/brite and brown adipose tissue serves as a mechanism to increase energy expenditure and resist obesity. DEXA and MRI analysis demonstrated significantly decreased total fat mass and fat/lean mass tissue ratio in male chow-fed sg/sg mice relative to wt mice. In addition, we observed increased Ucp1 expression in brown adipose and subcutaneous white adipose tissue but not in visceral adipose tissue from Rorα-deficient mice. Moreover, this was associated with significant increases in the expression of the mRNAs encoding the thermogenic genes (i.e., markers of brown and beige adipose) Pparα, Errα, Dio2, Acot11/Bfit, Cpt1β, and Cidea in the subcutaneous adipose in the sg/sg relative to WT mice. These changes in thermogenic gene expression involved the significantly increased expression of the (cell-fate controlling) histone-lysine N-methyltransferase 1 (Ehmt1), which stabilizes the Prdm16 transcriptional complex. Moreover, primary brown adipocytes from sg/sg mice displayed a higher metabolic rate, and further analysis was consistent with increased uncoupling. Finally, core body temperature analysis and infrared thermography demonstrated that the sg/sg mice maintained greater thermal control and cold tolerance relative to the WT littermates. We suggest that enhanced Ucp1 and thermogenic gene expression/activity may be an important contributor to the lean, obesity-resistant phenotype in Rorα-deficient mice.

  3. n-3多不饱和脂肪酸脱氢酶基因fat-1在人肺癌细胞H460内的表达%The Effect of n -3 Fatty Acid Dehydrogenase Gene fat - 1 Expression on Human Lung Cancer Cell H460

    Institute of Scientific and Technical Information of China (English)

    李芳芳; 葛银林; 李艳君; 单虎

    2011-01-01

    n-3多不饱和脂肪酸脱氢酶基因fat -1来自于秀丽线虫(C.elegans).为检测该基因在人肺癌细胞H460中的表达效果,本项研究构建了哺乳动物表达载体peDNA3.1(+)myc - HisA - fat -1,以Xfet polymer介导法转染到人肺癌细胞H460中,RT - PCR检测到有效的异源基因表达,MTT法证实基因表达能有效地抑制肺癌细胞的增殖率(P<0.05),气相色谱分析基因表达前后细胞中n - 6/n -3多不饱和脂肪酸比例降低(P<0.05),为将该基因用于癌症的转基因治疗奠定了基础.%fat -1 gene is a kind of n - 3 fatty acid dehydrogenase gene from Caenorhabditis elegans. In this stud-y, the eukaryotic expression vector pcDNA3.1 ( + ) myc - HisA - fat - 1 was constructed and expressed in human lung cancer cell H460. RT - PCR results showed that fat - 1 gene could expressed effectively in H460 cell and cell proliferation rate was markedly inhibited ( P <0.05). Moreover, fat - 1 gene could significantly decreased the ratio of cellular n -6 /n -3 PUFAs ( P <0.05).

  4. Macro fat and micro fat

    DEFF Research Database (Denmark)

    Li, Yanjun; Gaillard, Jonathan R; McLaughlin, Tracey;

    2015-01-01

    The adipose cell-size distribution is a quantitative characterization of adipose tissue morphology. At a population level, the adipose cell-size distribution is insulin-sensitivity dependent, and the observed correlation between obesity and insulin resistance is believed to play a key role in the...

  5. fat-1基因密码子优化及在家兔胎儿成纤维细胞中的初步表达%Codon optimization of fat-1 gene and its expression profiles in rabbit fetal fibroblast cells

    Institute of Scientific and Technical Information of China (English)

    周红梅; 王颖; 张立凡; 华绪川; 王争光; 徐宁迎; 郭晓令

    2011-01-01

    Based on the biased codon usage of rabbit, Caenorhabditis elegans fat-1 coding sequence referred from GenBank was optimized and synthesized, and fat-1 coding sequence was amplified from C. elegans by RT-PCR. The optimized fat-1 (named as opfat-1 ) and the amplified fat-1 coding sequence were cloned into green fluorescent protein expression vector pEGFP-C1 and transfected to rabbit fetal fibroblast cells (rFFCs) using LipofectamineTM, respectively. The impact factors were compared on transfection efficiency, including DNA, liposome dose as well as exposure time of the cells to DNA-liposome complexes. The optimized transfection condition was 2-3 μl LipofectamineTM and 0.8-1.0 μg DNA for 8 h transfection. The expressions of fusion protein and target genes were verified by GFP marker and RT-PCR assay. Transfection efficiency of opfat-1 was significantly increased compared with the wild type gene (.fat-1 coding sequence). The monoclonal cell lines were obtained by C-418 screening. Initial experiments demonstrated fat-1 coding sequence and opfat1 gene were both transcripted steadily in the rabbit fetal fibroblast cells by RT-PCR.%根据家兔基因密码子使用偏好性,对引自GenBank的秀丽隐杆线虫fat-1基因编码序列进行密码子优化,通过全基因合成的方法获得优化后的fat-1基因(命名为opfat-1);从秀丽隐杆线虫中RT-PCR扩增获得fat-1.将扩增的fat-1和合成的opfat-1基因分别构建到绿色荧光蛋白真核表达载体pEGFP-C1中.采用脂质体LipofectamineTM转染法将fat-1和opfat-1基因转入家兔胎儿成纤维细胞(Rabbit fetal fibroblast cells,rFFCs)中.对比不同DNA和转染试剂用量以及细胞暴露于DNA、转染试剂中作用时间探讨影响rFFCs转染效率的参数,经过优化,最优的rFFCs转染条件为:LipofectamineTM用量2~3μl,DNA量0.8~1.0μg,LipofectamineTM与DNA、细胞共培养时间为8 h.通过绿色荧光标记和RT-PCR检测转染细胞中融合蛋白和目的基因

  6. Increased Mitochondrial Activity in BMP7-Treated Brown Adipocytes, Due to Increased CPT1- and CD36-Mediated Fatty Acid Uptake

    OpenAIRE

    Townsend, Kristy L.; An, Ding; Lynes, Matthew D.; Huang, Tian Lian; Zhang, Hongbin; Goodyear, Laurie J.; Tseng, Yu-Hua

    2013-01-01

    Aims: Brown adipose tissue dissipates chemical energy in the form of heat and regulates triglyceride and glucose metabolism in the body. Factors that regulate fatty acid uptake and oxidation in brown adipocytes have not yet been fully elucidated. Bone morphogenetic protein 7 (BMP7) is a growth factor capable of inducing brown fat mitochondrial biogenesis during differentiation from adipocyte progenitors. Administration of BMP7 to mice also results in increased energy expenditure. To determine...

  7. Vertebral Bone Marrow Fat Is Positively Associated With Visceral Fat and Inversely Associated With IGF-1 in Obese Women

    OpenAIRE

    Bredella, Miriam A.; Torriani, Martin; Ghomi, Reza Hosseini; Thomas, Bijoy J.; Brick, Danielle J.; Gerweck, Anu V.; Clifford J Rosen; Klibanski, Anne; Miller, Karen K.

    2010-01-01

    Recent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiation into adipocytes or osteoblasts. Increased BMI appears to protect against osteoporosis. However, recent studies have suggested detrimental effects of visceral fat on bone health. Increased visceral fat may also be associated with decreased growth hormone (GH) and insulin-like growth factor 1 (IGF-1)...

  8. MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network

    DEFF Research Database (Denmark)

    Zhang, Hongbin; Guan, Meiping; Townsend, Kristy L;

    2015-01-01

    Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown...... adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning...... of subcutaneous white fat upon cold exposure. miR-455 activates AMPKα1 by targeting HIF1an, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis. Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and Necdin, initiating adipogenic differentiation. Taken together...

  9. Effects of vitamin a status on expression of ucp1 and brown/beige adipocyte-related genes in white adipose tissues of beef cattle.

    Science.gov (United States)

    Kanamori, Yohei; Yamada, Tomoya; Asano, Hiroki; Kida, Ryosuke; Qiao, Yuhang; Abd Eldaim, Mabrouk A; Tomonaga, Shozo; Matsui, Tohru; Funaba, Masayuki

    2014-09-01

    We previously reported the presence of brown/beige adipocytes in the white fat depots of mature cattle. The present study examined the effects of dietary vitamin A on the expression of brown/beige adipocyte-related genes in the white fat depots of fattening cattle. No significant differences were observed in the expression of Ucp1 between vitamin A-deficient cattle and control cattle. However, the expression of the other brown/beige adipocyte-related genes was slightly higher in the mesenteric fat depots of vitamin A-deficient cattle. The present results suggest that a vitamin A deficiency does not markedly affect the expression of Ucp1 in white fat depots, but imply that it may stimulate the emergence of beige adipocytes in the mesenteric fat depots of fattening cattle.

  10. Cell size and fat content of dietary-restricted Caenorhabditis elegans are regulated by ATX-2, an mTOR repressor.

    Science.gov (United States)

    Bar, Daniel Z; Charar, Chayki; Dorfman, Jehudith; Yadid, Tam; Tafforeau, Lionel; Lafontaine, Denis L J; Gruenbaum, Yosef

    2016-08-01

    Dietary restriction (DR) is a metabolic intervention that extends the lifespan of multiple species, including yeast, flies, nematodes, rodents, and, arguably, rhesus monkeys and humans. Hallmarks of lifelong DR are reductions in body size, fecundity, and fat accumulation, as well as slower development. We have identified atx-2, the Caenorhabditis elegans homolog of the human ATXN2L and ATXN2 genes, as the regulator of these multiple DR phenotypes. Down-regulation of atx-2 increases the body size, cell size, and fat content of dietary-restricted animals and speeds animal development, whereas overexpression of atx-2 is sufficient to reduce the body size and brood size of wild-type animals. atx-2 regulates the mechanistic target of rapamycin (mTOR) pathway, downstream of AMP-activated protein kinase (AMPK) and upstream of ribosomal protein S6 kinase and mTOR complex 1 (TORC1), by its direct association with Rab GDP dissociation inhibitor β, which likely regulates RHEB shuttling between GDP-bound and GTP-bound forms. Taken together, this work identifies a previously unknown mechanism regulating multiple aspects of DR, as well as unknown regulators of the mTOR pathway. They also extend our understanding of diet-dependent growth retardation, and offers a potential mechanism to treat obesity. PMID:27457958

  11. 湿性脂肪干细胞辅助自体颗粒脂肪移植五年临床回顾总结%The five-year review of autologous fat transplantation with stem cell auxiliary

    Institute of Scientific and Technical Information of China (English)

    刘乃军; 王艳

    2013-01-01

    Objective Retrospective summary of clinical experience of wet autologous fat particles grafting with the stromal vascular cells and adipose stem cell-assisted,autologous fat transplantation withwith fat stem cell auxiliary during January 2008~April2013.Methods In 549 cases,532 were completed by one stage of filling injection.In the other 17 cases,the second procedure had been done due to the bad fat survival.Almost of the cases got significantly improvements and achieved desired clinical effect.In 2 cases minor complications happened.Results Conclusion Follow-up of 1~5,this kind of fat autologous transplantation can improve the survival rate of transplanted fat.Conclusion Autologous fat transplantation with with fat stem cell auxiliary can significantly improve the survival rate of transplanted fat cells and get good long-term effect.%目的:回顾总结2008 ~ 2013年笔者行湿性脂肪干细胞辅助自体颗粒脂肪注射填充移植术五年的临床经验.方法:549例均采用湿性脂肪干细胞辅助自体颗粒脂肪移植术,单次注射填充移植完成532例(96.91%),17例(3.09%)脂肪存活率较低(30% ~ 40%)需二次注射填充移植完成.结果:本组仅2例(0.36%)出现轻微并发症,成活率和远期效果明显提高,取得预期临床效果.结论:随访1~5,采用规范的湿性肿胀技术和注射器吸脂法抽吸颗粒脂肪及湿性新鲜原代血管基质细胞和脂肪干细胞辅助自体颗粒脂肪移植注射填充移植技术效果明显持久,遵循其正确的临床操作原则和技术指南及标准操作流程,能明显提高移植脂肪成活率和良好远期效果,是一种切实、可行、有效的临床方法.

  12. Effects of Fat-soluble Extracts From Vegetable Powder and β-carotene on Proliferation and Apoptosis of Lung Cancer Cell YTMLC-90

    Institute of Scientific and Technical Information of China (English)

    QUAN-JUN LU; CHENG-YU HUANG; SHU-XIANG YAO; RUI-SHU WANG; XIAO-NA WU

    2003-01-01

    The aim of this investigation was to study the effects of fat-soluble extracts from vegetable powder (FEFVP) and β-carotene on the proliferation and apoptosis of cultured YTMLC-90lung cancer cells. Methods The lung cancer cells were continuously exposed to a broad range of concentration of FEFVP and β-carotene. The proliferation was evaluated in MTT test. The induction of apoptosis was evaluated by morphological change, DNA fragmentation analysis, and DNA content analysis combined with flow cytometric analysis. Results Both FEFVP and β-carotene were found to inhibit cell proliferation and to induce morphologic changes consistent with apoptosis in YTMLC-90 cancer cells, including cellular shrinkage, chromatin condensation and cytometric analysis revealed decreased DNA content and the presence of a sub-G1 apoptotic peak.Conclusion These findings are consistent with the induction of apoptosis. Moreover, the effects of FEFVP are stronger than those of β-carotene. FEFVP inhibits the growth of YTMLC-90 probably via the induction of apoptosis cancer cells.

  13. Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow,heart,liver,muscle,lung,derma,kidney,and fat

    Institute of Scientific and Technical Information of China (English)

    FANG Baijun; SONG Yongping; ZHAO Chunhua; SHI Mingxia; LIN Quande

    2007-01-01

    Previously,we reported that a cell population derived from human fetal bone marrow fBM),termed here Flk1+CD34-postembryonic pluripotent stem cells(PPSCs)that have the characteristics of mesenchymal stem cells (MSCs),could difierentiate into ectodermal,endodermal and mesodermal celI types at the single cell level in vitro,and that these cells could also difierentiate into the epithelium of liver,lung,gut,as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice.In this study,we further isolated pluripotent stem cells from human fetal heart,liver,muscle,lung,derma,kidney,and fat and then analyzed the characteristics and function of these stem cells.It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1+CD34-PPSCs.i.e.Flk1 and CD44 positive,GlyA,CD34,CD45,class I-HLA and HLA-DR negative.Morphologically,these cells were fibroblast-like and the doubling time was about 30 h.More importantly,culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes,osteocytes,neurons,gilal cells and hepatocytes.These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1+CD34-PPSCs can be selected and cultured from tissues other than the BM.This phenomenon may help explain the"stem cell plasticity"found in multiple human tissues.In addition,as fetal BM-derived Flk1+CD34-PPSCs,these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage difierentiation even after being expanded for more than 40 population doublings in vitro.Thus,they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.

  14. Searching for Brown Dwarf Outflows

    CERN Document Server

    Whelan, E T; Bacciotti, F; Randich, S; Natta, A

    2009-01-01

    As outflow activity in low mass protostars is strongly connected to ac- cretion it is reasonable to expect accreting brown dwarfs to also be driving out- flows. In the last three years we have searched for brown dwarf outflows using high quality optical spectra obtained with UVES on the VLT and the technique of spectro-astrometry. To date five brown dwarf outflows have been discovered. Here the method is discussed and the results to date outlined.

  15. Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E2 signaling in fat stromal cells

    Directory of Open Access Journals (Sweden)

    Ruan Diana

    2012-08-01

    Full Text Available Abstract Background The molecular mechanisms of dietary oils (such as fish oil and unsaturated fatty acids, which are widely used by the public for anti-inflammation and vascular protection, have not been settled yet. In this study, prostaglandin E2 (PGE2-mediated calcium signaling was used to screen dietary oils and eight unsaturated fatty acids for identification of their anti-inflammatory mechanisms. Isolated fat/stromal cells expressing endogenous PGE2 receptors and an HEK293 cell line specifically expressing the recombinant human PGE2 receptor subtype-1 (EP1 were cultured and used in live cell calcium signaling assays. The different dietary oils and unsaturated fatty acids were used to affect cell signaling under the specific stimulation of a pathological amount of inflammatory PGE2. Results It was identified that fish oil best inhibited the PGE2 signaling in the primary cultured stromal cells. Second, docosahexaenoic acid (DHA, found in abundance in fish oil, was identified as a key factor of inhibition of PGE2 signaling. Eicosapentaenoic acid (EPA, another major fatty acid found in fish oil and tested in this study was found to have small effect on EP1 signaling. The study suggested one of the four PGE2 subtype receptors, EP1 as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP1 expressed in HEK293 cells as a target. Conclusion This study demonstrated the new mechanism behind the positive effects of dietary fish oils in inhibiting inflammation originates from the rich concentration of DHA, which can directly inhibit the inflammatory EP1-mediated PGE2 receptor signaling, and that the inflammatory response stimulated by PGE2 in the fat stromal cells, which directly related to metabolic diseases, could be down regulated by fish oil and DHA. These findings also provided direct evidence to support the use of dietary oils and unsaturated fatty acids for protection against heart

  16. fat-1基因对乳腺癌细胞的增殖抑制作用%Inhibition of fat-1 Gene on Proliferation of Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    李馨; 王秀丽; 田润华; 刘颖; 侯琳; 耿芳宋; 葛银林

    2005-01-01

    目的: 研究fat-1基因在人乳腺癌细胞内的表达、功能及其对乳腺癌细胞增殖的影响.方法: 把fat-1 基因插入到腺病毒的穿梭载体中,与骨架载体同源重组,构建腺病毒重组载体 (Ad.GFP.fat1),将通过包装细胞系(293)产生的腺病毒感染人乳腺癌株QMR2细胞.提取细胞的总RNA,以fat-1的反义mRNA 作探针,用Northern Blot检测fat-1 基因在人乳腺癌株QMR2细胞内的表达.流式细胞仪分析n-3脂肪酸脱氢酶对人乳腺癌株QMR2细胞增殖的影响.气象色谱仪分析n-3脂肪酸脱氢酶对人乳腺癌株QMR2细胞的n-6 PUFAs/n-3 PUFAs含量影响.结果: fat-1 基因在人乳腺癌株QMR2细胞中能有效异源表达,2 d后检测到fat-1mRNA的条带.fat-1基因抑制了人乳腺癌株QMR2细胞的增殖,降低了20%(P<0.05);同时降低了人乳腺癌株QMR2细胞n-6 PUFAs/n-3 PUFAs含量降低.结论: 腺病毒介导的fat-1 基因能在人乳腺癌株QMR2细胞内有效异源表达,且抑制人乳腺癌株QMR2细胞的增殖.

  17. Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet.

    Science.gov (United States)

    Kadowaki, Tomoko; Kido, Mizuho A; Hatakeyama, Junko; Okamoto, Kuniaki; Tsukuba, Takayuki; Yamamoto, Kenji

    2014-03-28

    Cathepsin E is an intracellular aspartic proteinase, which is predominantly distributed in immune-related and epithelial cells. However, the role of the enzyme in adipose tissues remains unknown. In this study, we investigated the characteristics of cathepsin E-deficient (CatE(-/-)) mice fed a high-fat diet (HFD), as a mouse model of obesity. HFD-fed CatE(-/-) mice displayed reduced body weight gain and defective development of white adipose tissue (WAT) and brown adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced CatE(-/-) mice showed abnormal lipid accumulation in non-adipose tissues characterized by hepatomegaly, which is probably due to defective adipose tissue development. Detailed pathological and biochemical analyses showed that hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD-induced CatE(-/-) mice. In fat-induced CatE(-/-) mice, the number of macrophages infiltrating into WAT was significantly lower than in fat-induced wild-type mice. Thus, the impaired adipose tissue development in HFD-induced CatE(-/-) mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.

  18. Abdominal fat reducing outcome of exercise training: fat burning or hydrocarbon source redistribution?

    Science.gov (United States)

    Kuo, Chia-Hua; Harris, M Brennan

    2016-07-01

    Fat burning, defined by fatty acid oxidation into carbon dioxide, is the most described hypothesis to explain the actual abdominal fat reducing outcome of exercise training. This hypothesis is strengthened by evidence of increased whole-body lipolysis during exercise. As a result, aerobic training is widely recommended for obesity management. This intuition raises several paradoxes: first, both aerobic and resistance exercise training do not actually elevate 24 h fat oxidation, according to data from chamber-based indirect calorimetry. Second, anaerobic high-intensity intermittent training produces greater abdominal fat reduction than continuous aerobic training at similar amounts of energy expenditure. Third, significant body fat reduction in athletes occurs when oxygen supply decreases to inhibit fat burning during altitude-induced hypoxia exposure at the same training volume. Lack of oxygen increases post-meal blood distribution to human skeletal muscle, suggesting that shifting the postprandial hydrocarbons towards skeletal muscle away from adipose tissue might be more important than fat burning in decreasing abdominal fat. Creating a negative energy balance in fat cells due to competition of skeletal muscle for circulating hydrocarbon sources may be a better model to explain the abdominal fat reducing outcome of exercise than the fat-burning model. PMID:27152424

  19. Mesenchymal progenitor cells derived from synovium and infrapatellar fat pad as a source for superficial zone cartilage tissue engineering: analysis of superficial zone protein/lubricin expression.

    Science.gov (United States)

    Lee, Sang Yang; Nakagawa, Toshiyuki; Reddi, A Hari

    2010-01-01

    Superficial zone protein (SZP) is a boundary lubricant of articular cartilage in joints. As SZP at the surface of articular cartilage plays an important role in the normal function of synovial joints, the localization of SZP-secreting cells at the surface of tissue-engineered cartilage is prerequisite. The aim of this study was to identify suitable progenitor cell sources for tissue engineering of superficial zone cartilage. We investigated whether mesenchymal progenitor cells (MPCs) from synovium and infrapatellar fat pad (IFP) have the potential for secretion of SZP after chondrogenic differentiation in an aggregate pellet culture system. SZP was immunolocalized in pellets from synovium-MPCs and IFP-MPCs. The enzyme-linked immunosorbent assay analysis of SZP demonstrated that chondrogenically differentiated synovium-MPC and IFP-MPC pellets secreted SZP into media. Real-time polymerase chain reaction analysis showed significant upregulation of SZP mRNA in synovium-MPC and IFP-MPC pellets after chondrogenic differentiation. The synovium-MPCs demonstrated the higher colony-forming, proliferative, and chondrogenic potential, and exhibited greater SZP secretion after chondrogenic induction compared with IFP-MPCs. In conclusion, both synovium and IFP are promising cell sources for tissue engineering of superficial zone cartilage.

  20. Fasting induces a subcutaneous-to-visceral fat switch mediated by microRNA-149-3p and suppression of PRDM16.

    Science.gov (United States)

    Ding, Hanying; Zheng, Shasha; Garcia-Ruiz, Daniel; Hou, Dongxia; Wei, Zhe; Liao, Zhicong; Li, Limin; Zhang, Yujing; Han, Xiao; Zen, Ke; Zhang, Chen-Yu; Li, Jing; Jiang, Xiaohong

    2016-01-01

    Visceral adiposity is strongly associated with metabolic disease risk, whereas subcutaneous adiposity is comparatively benign. However, their relative physiological importance in energy homeostasis remains unclear. Here, we show that after 24-h fasting, the subcutaneous adipose tissue of mice acquires key properties of visceral fat. During this fast-induced 'visceralization', upregulation of miR-149-3p directly targets PR domain containing 16 (PRDM16), a key coregulatory protein required for the 'browning' of white fat. In cultured inguinal preadipocytes, overexpression of miR-149-3p promotes a visceral-like switch during cell differentiation. Mice deficient in miR-149-3p display an increase in whole-body energy expenditure, with enhanced thermogenesis of inguinal fat. However, a visceral-like adipose phenotype is observed in inguinal depots overexpressing miR-149-3p. These results indicate that in addition to the capacity of 'browning' to defend against hypothermia during cold exposure, the subcutaneous adipose depot is also capable of 'whitening' to preserve energy during fasting, presumably to maintain energy balance, via miR-149-3p-mediated regulation of PRDM16. PMID:27240637

  1. Expression of cell wall related genes in basal and ear internodes of silking brown-midrib-3, caffeic acid O-methyltransferase (COMT down-regulated, and normal maize plants

    Directory of Open Access Journals (Sweden)

    Martinant Jean-Pierre

    2008-06-01

    Full Text Available Abstract Background Silage maize is a major forage and energy resource for cattle feeding, and several studies have shown that lignin content and structure are the determining factors in forage maize feeding value. In maize, four natural brown-midrib mutants have modified lignin content, lignin structure and cell wall digestibility. The greatest lignin reduction and the highest cell wall digestibility were observed in the brown-midrib-3 (bm3 mutant, which is disrupted in the caffeic acid O-methyltransferase (COMT gene. Results Expression of cell wall related genes was investigated in basal and ear internodes of normal, COMT antisens (AS225, and bm3 maize plants of the INRA F2 line. A cell wall macro-array was developed with 651 gene specific tags of genes specifically involved in cell wall biogenesis. When comparing basal (older lignifying and ear (younger lignifying internodes of the normal line, all genes known to be involved in constitutive monolignol biosynthesis had a higher expression in younger ear internodes. The expression of the COMT gene was heavily reduced, especially in the younger lignifying tissues of the ear internode. Despite the fact that AS225 transgene expression was driven only in sclerenchyma tissues, COMT expression was also heavily reduced in AS225 ear and basal internodes. COMT disruption or down-regulation led to differential expressions of a few lignin pathway genes, which were all over-expressed, except for a phenylalanine ammonia-lyase gene. More unexpectedly, several transcription factor genes, cell signaling genes, transport and detoxification genes, genes involved in cell wall carbohydrate metabolism and genes encoding cell wall proteins, were differentially expressed, and mostly over-expressed, in COMT-deficient plants. Conclusion Differential gene expressions in COMT-deficient plants highlighted a probable disturbance in cell wall assembly. In addition, the gene expressions suggested modified chronology of the

  2. Binding of immunoglobulin G from patients with autoimmune thyroid diseases to solubilized guinea pig fat cell membranes crosslinked with 125I-TSH

    International Nuclear Information System (INIS)

    Binding of immunoglobulin G (IgG) to Triton-solubilized fat cell membranes crosslinked with 125I-TSH was studied by an indirect immunoprecipitation method. Guinea pig fat cell membranes (FCM) containing TSH receptors with an association constant of 1.92 x 109 M-1 were first reacted with 125I-TSH, then treated with a crosslinker, dissuccinimidyl suberate. The dissociation of 125I-TSH from the crosslinked 125I-TSH-FCM complexes due to the addition of 100 mU/ml unlabeled TSH was 9.0 %, while it was 33 % without the treatment. To the Triton-solubilized FCM crosslinked with 125I-TSH, 50 μg each of IgG from 20 normal controls, 20 patients with Graves' disease and 20 with Hashimoto's disease was added and precipitation was effected by adding antihuman IgG. In patients with Graves' disease, 125I-TSH-FCM complexes immunoprecipitated ranged from 1.10 to 4.18 % with an average of 2.4 ± 0.99 (S. D.) % which was significantly higher than those in normal controls (1.6 ± 0.29 %). The values in the patients with Hashimoto's disease averaged 1.7 ± 0.53 (S. D.) which did not differ significantly from those of controls. The value did not correlate with either TSH-binding inhibiting activities or titers of anti-microsomal antibodies. These data suggest the presence of TSH-receptor antibodies which react with antigens other than TSH-binding sites in the patients with Graves' disease. (author)

  3. Trans Fat Now Listed With Saturated Fat and Cholesterol

    Science.gov (United States)

    ... Trans Fat Now Listed With Saturated Fat and Cholesterol Share Tweet Linkedin Pin it More sharing options ... I Do About Saturated Fat, Trans Fat, and Cholesterol? When comparing foods, look at the Nutrition Facts ...

  4. Playing with bone and fat

    DEFF Research Database (Denmark)

    Gimble, Jeffrey M.; Zvonic, Sanjin; Floyd, Z. Elisabeth;

    2006-01-01

    The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or s...... or stromal cells to the adipocyte and osteoblast lineage pathways. In this review, we focus on the recent literature exploring the mechanisms underlying these differentiation events and discuss their implications relevant to osteoporosis and regenerative medicine....

  5. Facts about monounsaturated fats

    Science.gov (United States)

    ... amounts of monounsaturated fats include: Nuts Avocado Canola oil Olive oil Safflower oil (high oleic) Sunflower oil Peanut oil ... and sandwiches. Replace butter and solid fats with olive or canola oil.

  6. Facts about saturated fats

    Science.gov (United States)

    ... at room temperature. Foods like butter, palm and coconut oils, cheese, and red meat have high amounts of saturated fat. Too much saturated fat in your diet can lead to heart disease and other health problems.

  7. Facts about trans fats

    Science.gov (United States)

    ... of servings you eat in one sitting. Many fast food restaurants use solid oils with trans fat for ... frozen yogurt, milk shakes, and pudding Snack foods Fast food Solid fats, such as shortening and margarine Nondairy ...

  8. Dietary fats explained

    Science.gov (United States)

    ... fats raise your LDL ("bad") cholesterol level. High LDL cholesterol puts you at risk for heart attack, stroke, ... instead of saturated fats can help lower your LDL cholesterol. Most vegetable oils that are liquid at room ...

  9. Lack of TRPV2 impairs thermogenesis in mouse brown adipose tissue.

    Science.gov (United States)

    Sun, Wuping; Uchida, Kunitoshi; Suzuki, Yoshiro; Zhou, Yiming; Kim, Minji; Takayama, Yasunori; Takahashi, Nobuyuki; Goto, Tsuyoshi; Wakabayashi, Shigeo; Kawada, Teruo; Iwata, Yuko; Tominaga, Makoto

    2016-03-01

    Brown adipose tissue (BAT), a major site for mammalian non-shivering thermogenesis, could be a target for prevention and treatment of human obesity. Transient receptor potential vanilloid 2 (TRPV2), a Ca(2+)-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. Here, we show that TRPV2 is expressed in brown adipocytes and that mRNA levels of thermogenic genes are reduced in both cultured brown adipocytes and BAT from TRPV2 knockout (TRPV2KO) mice. The induction of thermogenic genes in response to β-adrenergic receptor stimulation is also decreased in TRPV2KO brown adipocytes and suppressed by reduced intracellular Ca(2+) concentrations in wild-type brown adipocytes. In addition, TRPV2KO mice have more white adipose tissue and larger brown adipocytes and show cold intolerance, and lower BAT temperature increases in response to β-adrenergic receptor stimulation. Furthermore, TRPV2KO mice have increased body weight and fat upon high-fat-diet treatment. Based on these findings, we conclude that TRPV2 has a role in BAT thermogenesis and could be a target for human obesity therapy. PMID:26882545

  10. Fat embolism syndrome

    OpenAIRE

    Jacob George; Reeba George; Dixit, R; Gupta, R C; Gupta, N.

    1997-01-01

    Fat embolism syndrome, an important contributor to the development of acute respiratory distress syndrome, has been associated with both traumatic and nontraumatic disorders. Fat embolization after long bone trauma is probably common as a subclinical event. Fat emboli can deform and pass through the lungs, resulting in systemic embolization, most commonly to the brain and kidneys. The diagnosis of fat embolism syndrome is based on the patient’s history, supported by clinical signs of pulmonar...

  11. Tune Your Brown Clustering, Please

    DEFF Research Database (Denmark)

    Derczynski, Leon; Chester, Sean; Bøgh, Kenneth Sejdenfaden

    2015-01-01

    unexplored. Accordingly, we present information for practitioners on the behaviour of Brown clustering in order to assist hyper-parametre tuning, in the form of a theoretical model of Brown clustering utility. This model is then evaluated empirically in two sequence labelling tasks over two text types. We...

  12. Drosophila lowfat, a novel modulator of Fat signaling

    OpenAIRE

    Mao, Yaopan; Kucuk, Binnaz; Irvine, Kenneth D.

    2009-01-01

    The Fat-Hippo-Warts signaling network regulates both transcription and planar cell polarity. Despite its crucial importance to the normal control of growth and planar polarity, we have only a limited understanding of the mechanisms that regulate Fat. We report here the identification of a conserved cytoplasmic protein, Lowfat (Lft), as a modulator of Fat signaling. Drosophila Lft, and its human homologs LIX1 and LIX1-like, bind to the cytoplasmic domains of the Fat lig...

  13. High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes in Rats Impacts Osteogenesis and Wnt Signaling in Bone Marrow Stromal Cells.

    Science.gov (United States)

    Qian, Chao; Zhu, Chenyuan; Yu, Weiqiang; Jiang, Xinquan; Zhang, Fuqiang

    2015-01-01

    Bone regeneration disorders are a significant problem in patients with type 2 diabetes mellitus. Bone marrow stromal cells (BMSCs) are recognized as ideal seed cells for tissue engineering because they can stimulate osteogenesis during bone regeneration. Therefore, the aim of this study was to investigate the osteogenic potential of BMSCs derived from type 2 diabetic rats and the pathogenic characteristics of dysfunctional BMSCs that affect osteogenesis. BMSCs were isolated from normal and high-fat diet+streptozotocin-induced type 2 diabetic rats. Cell metabolic activity, alkaline phosphatase (ALP) activity, mineralization and osteogenic gene expression were reduced in the type 2 diabetic rat BMSCs. The expression levels of Wnt signaling genes, such as β-catenin, cyclin D1 and c-myc, were also significantly decreased in the type 2 diabetic rat BMSCs, but the expression of GSK3β remained unchanged. The derived BMSCs were cultured on calcium phosphate cement (CPC) scaffolds and placed subcutaneously into nude mice for eight weeks; they were detected at a low level in newly formed bone. The osteogenic potential of the type 2 diabetic rat BMSCs was not impaired by the culture environment, but it was impaired by inhibition of the Wnt signaling pathway, likely due to an insufficient accumulation of β-catenin rather than because of GSK3β stimulation. Using BMSCs derived from diabetic subjects could offer an alternative method of regenerating bone together with the use of supplementary growth factors to stimulate the Wnt signaling pathway. PMID:26296196

  14. Cell chamber structure and influences factors analysis on sugarcane stem tips browning in vitro%甘蔗茎尖离体培养褐变影响因素及细胞区室结构分析

    Institute of Scientific and Technical Information of China (English)

    杨柳; 唐云仙; 廖芬; 汪淼; 梁永检; 杨丽涛; 黄东亮; 李杨瑞

    2016-01-01

    This research was mainly carried out to analyze the mechanism of sugarcane stem tip browning in vitro culture through investigating the influences factors which relate to phenolic browning and observing stem tip cellular compart-ments structure changes in the process of browning. Sugarcane variety ROC 22 which provided by sugarcane research in-stitute of Guangxi Academy of Agricultural Sciences was selected as experiment material. The result showed that different axillary buds obtained obviously different induction survival rates, the more fresh buds resulted in the more high survival rate, the first position bud got the highest survival rate, that is to mean the more fresh bud get the more higher induction survival rate;the induction survival rate was not effected by different explants collecting seasons;pre-germination time 4 weeks resulted higher induction survival rate, and obtained significant difference compared with other pre-germination time treatments. Different buds with different pre-germination time treatments had obvious different total phenolic com-pounds content, the longer pre-germination time resulted in the lower phenolic compounds accumulated in stem tip cells, pre-germination time for 2 weeks and 3 weeks obtained higher total phenolic compounds in stem tip cells at different posi-tion buds, while pre-germination for 4 weeks and 5 weeks got low total phenolic compounds content, therefore, sugar-cane axillary bud was pre-germinated for 4 weeks is a better period for induction tissue culture;stem tip total phenolic compounds content was not effected by explants collecting season;polyphenol oxidase acitivity changed significantly in different axillary buds with different pre-germination time treatments, lower polyphenol oxidase acitivity were obtained in 1-6 position buds with 2 weeks pre-germinated treatment and in 3-6 position buds with 4 weeks pre-germinated treat-ment;while higher polyphenol oxidase acitivity were obtained in 1-3 position buds

  15. Platelet function in brown bear (Ursus arctos compared to man

    Directory of Open Access Journals (Sweden)

    Särndahl Eva

    2010-06-01

    Full Text Available Abstract Background Information on hemostasis and platelet function in brown bear (Ursus arctos is of importance for understanding the physiological, protective changes during hibernation. Objective The study objective was to document platelet activity values in brown bears shortly after leaving the den and compare them to platelet function in healthy humans. Methods Blood was drawn from immobilized wild brown bears 7-10 days after leaving the den in mid April. Blood samples from healthy human adults before and after clopidogrel and acetylsalicylic acid administration served as control. We analyzed blood samples by standard blood testing and platelet aggregation was quantified after stimulation with various agonists using multiple electrode aggregometry within 3 hours of sampling. Results Blood samples were collected from 6 bears (3 females between 1 and 16 years old and from 10 healthy humans. Results of adenosine diphosphate, aspirin, and thrombin receptor activating peptide tests in bears were all half or less of those in humans. Platelet and white blood cell counts did not differ between species but brown bears had more and smaller red blood cells compared with humans. Conclusion Using three different tests, we conclude that platelet function is lower in brown bears compared to humans. Our findings represent the first descriptive study on platelet function in brown bears and may contribute to explain how bears can endure denning without obvious thrombus building. However, the possibility that our findings reflect test-dependent and not true biological variations in platelet reactivity needs further studies.

  16. An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes.

    Science.gov (United States)

    Isidor, Marie S; Winther, Sally; Basse, Astrid L; Petersen, M Christine H; Cannon, Barbara; Nedergaard, Jan; Hansen, Jacob B

    2016-01-01

    Brown adipose tissue is a promising therapeutic target for opposing obesity, glucose intolerance and insulin resistance. The ability to modulate gene expression in mature brown adipocytes is important to understand brown adipocyte function and delineate novel regulatory mechanisms of non-shivering thermogenesis. The aim of this study was to optimize a lipofection-based small interfering RNA (siRNA) transfection protocol for efficient silencing of gene expression in mature brown adipocytes. We determined that a critical parameter was to deliver the siRNA to mature adipocytes by reverse transfection, i.e. transfection of non-adherent cells. Using this protocol, we effectively knocked down both high- and low-abundance transcripts in a model of mature brown adipocytes (WT-1) as well as in primary mature mouse brown adipocytes. A functional consequence of the knockdown was confirmed by an attenuated increase in uncoupled respiration (thermogenesis) in response to β-adrenergic stimulation of mature WT-1 brown adipocytes transfected with uncoupling protein 1 siRNA. Efficient gene silencing was also obtained in various mouse and human white adipocyte models (3T3-L1, primary mouse white adipocytes, hMADS) with the ability to undergo "browning." In summary, we report an easy and versatile reverse siRNA transfection protocol to achieve specific silencing of gene expression in various models of mature brown and browning-competent white adipocytes, including primary cells.

  17. An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes.

    Science.gov (United States)

    Isidor, Marie S; Winther, Sally; Basse, Astrid L; Petersen, M Christine H; Cannon, Barbara; Nedergaard, Jan; Hansen, Jacob B

    2016-01-01

    Brown adipose tissue is a promising therapeutic target for opposing obesity, glucose intolerance and insulin resistance. The ability to modulate gene expression in mature brown adipocytes is important to understand brown adipocyte function and delineate novel regulatory mechanisms of non-shivering thermogenesis. The aim of this study was to optimize a lipofection-based small interfering RNA (siRNA) transfection protocol for efficient silencing of gene expression in mature brown adipocytes. We determined that a critical parameter was to deliver the siRNA to mature adipocytes by reverse transfection, i.e. transfection of non-adherent cells. Using this protocol, we effectively knocked down both high- and low-abundance transcripts in a model of mature brown adipocytes (WT-1) as well as in primary mature mouse brown adipocytes. A functional consequence of the knockdown was confirmed by an attenuated increase in uncoupled respiration (thermogenesis) in response to β-adrenergic stimulation of mature WT-1 brown adipocytes transfected with uncoupling protein 1 siRNA. Efficient gene silencing was also obtained in various mouse and human white adipocyte models (3T3-L1, primary mouse white adipocytes, hMADS) with the ability to undergo "browning." In summary, we report an easy and versatile reverse siRNA transfection protocol to achieve specific silencing of gene expression in various models of mature brown and browning-competent white adipocytes, including primary cells. PMID:27386153

  18. A Fat Higgs with a Fat Top

    CERN Document Server

    Delgado, A; Delgado, Antonio; Tait, Tim M.P.

    2005-01-01

    A new variant of the supersymmetric Fat Higgs model is presented in which the MSSM Higgses as well as the top quark are composite. The underlying theory is an s-confining SU(3) gauge theory with the MSSM gauge groups realized as gauged sub-groups of the chiral flavor symmetries. This motivates the large Yukawas necessary for the large top mass and SM-like Higgs of mass>>M_Z in a natural way as the residual of the strong dynamics responsible for the composites. This removes fine-tuning associated with these couplings present in the original Fat Higgs and New Fat Higgs models, respectively.

  19. Silica nanoparticles inhibit brown adipocyte differentiation via regulation of p38 phosphorylation

    Science.gov (United States)

    Son, Min Jeong; Kim, Won Kon; Kwak, Minjeong; Oh, Kyoung-Jin; Chang, Won Seok; Min, Jeong-Ki; Lee, Sang Chul; Song, Nam Woong; Bae, Kwang-Hee

    2015-10-01

    Nanoparticles are of great interest due to their wide variety of biomedical and bioengineering applications. However, they affect cellular differentiation and/or intracellular signaling when applied and exposed to target organisms or cells. The brown adipocyte is a cell type important in energy homeostasis and thus closely related to obesity. In this study, we assessed the effects of silica nanoparticles (SNPs) on brown adipocyte differentiation. The results clearly showed that brown adipocyte differentiation was significantly repressed by exposure to SNPs. The brown adipocyte-specific genes as well as mitochondrial content were also markedly reduced. Additionally, SNPs led to suppressed p38 phosphorylation during brown adipocyte differentiation. These effects depend on the size of SNPs. Taken together, these results lead us to suggest that SNP has anti-brown adipogenic effect in a size-dependent manner via regulation of p38 phosphorylation.

  20. Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction.

    Science.gov (United States)

    Manimaran, K; Sharma, Rohini; Sankaranarayanan, S; Perumal, S Mahendra

    2016-01-01

    Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14-year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1(st) month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10(th) month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor. PMID:27563616

  1. Kupffer cells ameliorate hepatic insulin resistance induced by high-fat diet rich in monounsaturated fatty acids: the evidence for the involvement of alternatively activated macrophages

    Directory of Open Access Journals (Sweden)

    Papackova Zuzana

    2012-03-01

    Full Text Available Abstract Background Resident macrophages (Kupffer cells, KCs in the liver can undergo both pro- or anti-inflammatory activation pathway and exert either beneficiary or detrimental effects on liver metabolism. Until now, their role in the metabolically dysfunctional state of steatosis remains enigmatic. Aim of our study was to characterize the role of KCs in relation to the onset of hepatic insulin resistance induced by a high-fat (HF diet rich in monounsaturated fatty acids. Methods Male Wistar rats were fed either standard (SD or high-fat (HF diet for 4 weeks. Half of the animals were subjected to the acute GdCl3 treatment 24 and 72 hrs prior to the end of the experiment in order to induce the reduction of KCs population. We determined the effect of HF diet on activation status of liver macrophages and on the changes in hepatic insulin sensitivity and triacylglycerol metabolism imposed by acute KCs depletion by GdCl3. Results We found that a HF diet rich in MUFA itself triggers an alternative but not the classical activation program in KCs. In a steatotic, but not in normal liver, a reduction of the KCs population was associated with a decrease of alternative activation and with a shift towards the expression of pro-inflammatory activation markers, with the increased autophagy, elevated lysosomal lipolysis, increased formation of DAG, PKCε activation and marked exacerbation of HF diet-induced hepatic insulin resistance. Conclusions We propose that in the presence of a high MUFA content the population of alternatively activated resident liver macrophages may mediate beneficial effects on liver insulin sensitivity and alleviate the metabolic disturbances imposed by HF diet feeding and steatosis. Our data indicate that macrophage polarization towards an alternative state might be a useful strategy for treating type 2 diabetes.

  2. 棕色脂肪的调节——针对代谢性疾病的新一代治疗方法探讨%Metabolic regulation of brown adipose : a possible new therapeutic approach for metabolic diseases

    Institute of Scientific and Technical Information of China (English)

    肖正华

    2014-01-01

    Browning of white adipose tissue(WAT) is expected to become a possible new therapeutic means for diabetes mellitus and other metabolic diseases in future,because brown adipose tissue (BAT) has attracted scientific interest as an anti-diabetic tissue owning to its ability to dissipate energy as heat.In this article,we reviewed the characteristics of brown fat cells,the major transcription factor and the stimulating factor during browning of WAT,as well as their potential mechanisms and research directions.%白色脂肪棕色(米色)化有望成为未来糖尿病等代谢性疾病治疗一种可能的新方式.本文就棕色脂肪细胞的特点、以及白色脂肪棕色化过程中主要转录因子、刺激因子及可能机制和研究方向进行概述.

  3. Inhibitory effects of fat-1 gene on the proliferation of Ishikawa endometrial cancer cells%fat-1基因对子宫内膜癌Ishikawa细胞的增殖抑制作用

    Institute of Scientific and Technical Information of China (English)

    王宇辰; 陆晓媛

    2015-01-01

    目的:探讨fat-1基因在子宫内膜癌Ishikawa细胞中表达及对子宫内膜癌细胞增殖的影响。方法用脂质体介导的方法将含有fat-1基因和荧光蛋白标记基因的真核表达载体pEGFP-fat-1质粒转染子宫内膜癌Ishikawa细胞,以荧光显微镜观察及RT-PCR方法检测fat-1基因的表达情况,CCK-8法分析fat-1基因对子宫内膜癌Ishikawa细胞增殖的影响。结果 fat-1基因在人子宫内膜癌Ishikawa细胞内有效异源表达,fat-1基因抑制了人子宫内膜癌Ishikawa细胞的增殖(与对照组比较P<0.05)。结论 fat-1基因能够抑制人子宫内膜癌Ishikawa细胞的增殖。%Obective To investigate the effects of fat-1 gene on the proliferation of Ishikawa endometrial cancer cells.Methods The eukaryotic expression vector pEGFP-fat-1 containing fat-1 gene and fluorescent probes was transfected into Ishikawa cells using the lipoid-mediated method.The expression of fat-1 was detected by fluorescent labeling and RT-PCR.The inhibitory effects of fat-1 gene on the proliferation of Ishikawa cells were observed by CCK-8 method.Results The expression of fat-1 gene was detected in Ishikawa cells after transfection, and this gene in-hibited the proliferation of the cells (P<0.05).Conclusion The gene fat-1 can effectively bloack the proliferation of Ishikawa cells.

  4. Controversies in fat perception.

    Science.gov (United States)

    Heinze, Jaana M; Preissl, Hubert; Fritsche, Andreas; Frank, Sabine

    2015-12-01

    Nutritional fat is one of the most controversial topics in nutritional research, particularly against the background of obesity. Studies investigating fat taste perception have revealed several associations with sensory, genetic, and personal factors (e.g. BMI). However, neuronal activation patterns, which are known to be highly sensitive to different tastes as well as to BMI differences, have not yet been included in the scheme of fat taste perception. We will therefore provide a comprehensive survey of the sensory, genetic, and personal factors associated with fat taste perception and highlight the benefits of applying neuroimaging research. We will also give a critical overview of studies investigating sensory fat perception and the challenges resulting from multifaceted methodological approaches. In conclusion, we will discuss a multifactorial approach to fat perception to gain a better understanding of the underlying mechanisms that cause varying fat sensitivity which could be responsible for overeating. Such knowledge might be beneficial in new treatment strategies for obesity and overweight.

  5. Effect of overexpression of uncoupling protein 1 on brown adipose tissue in aP2-Ucp mice

    International Nuclear Information System (INIS)

    The aim of the present study was assess the function of mitochondria in brown fat of the transgenic animals in order to explain the functional involution of brown adipose tissue (BAT). This study was based on measurements of transmembrane electrochemical potential (Δψ) and estimation of [3H]GDP binding to isolated brown fat mitochondria, as well as on immunochemical analysis of trans-gene expression. Fluorescent cationic dye Rhodamine 123 was used to follow the changes in Δψ of isolated brown fat mitochondria. The fluorescence is quenched as the dye is accumulated in mitochondria in response to membrane energization. Titration by the inhibitory ligand of mitochondrial uncoupling protein 1 (UCP1), GDP (in presence of substrate), indicated a 3-fold lower sensitivity to GDP in mitochondria from transgenic compared with non-transgenic animals. Binding of [3H]GDP to both types of brown fat mitochondria was measured. Maximum number of specific GDP-binding sites was estimated from Scatchard plots. In accordance with the activity measurements, number of GDP-binding sites was approximately 3- to 5-fold higher in mitochondria isolated from the transgenic animals. (authors)

  6. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.

    Science.gov (United States)

    Verdeguer, Francisco; Soustek, Meghan S; Hatting, Maximilian; Blättler, Sharon M; McDonald, Devin; Barrow, Joeva J; Puigserver, Pere

    2016-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  7. Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad

    OpenAIRE

    Nickerson, Nicole K.; Mohammad, Khalid S.; Gilmore, Jennifer L.; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A.; Foley, John

    2012-01-01

    Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and oste...

  8. Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway.

    Science.gov (United States)

    Zhu, Yaping; Shen, Jiaqi; Gao, Liyan; Feng, Youji

    2016-04-01

    Extensive exposure to estrogen is generally acknowledged as a risk factor for endometrial cancer. Given that the accumulation of adipocytes also contributes to the increased production of estrogen, in the present study, we evaluated the expression of the fat mass and obesity-associated (FTO) gene in endometrial tumor tissues and further explored the mechanism of how estrogen facilitates FTO nuclear localization and promotes endometrial cancer cell proliferation. Immunohistochemical (IHC) staining assay was used to detect the FTO expression in endometrial tumor samples. Western blotting was performed to investigate the mechanism of estrogen-induced FTO nuclear localization. siRNA was used to knock down ERα and further explore its role in FTO nuclear localization. MTT assay was carried out to determine cell proliferation. We found that FTO was overexpressed in endometrial carcinoma tissues and served as a poor prognostic marker. Additionally, estrogen induced FTO nuclear accumulation via the mTOR signaling pathway and the nuclear localization was ERα-dependent, which contributed to enhanced proliferative activity. Therefore, the present study provides new insight into the mechanisms of estrogen-induced proliferation, implying the possibility of using FTO as a potential therapeutic target for the treatment of endometrial cancer.

  9. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

    Science.gov (United States)

    Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

    2016-01-15

    Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.

  10. Moderate Exercise Restores Pancreatic Beta-Cell Function and Autonomic Nervous System Activity in Obese Rats Induced by High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Rodrigo Mello Gomes

    2013-08-01

    Full Text Available Background/Aims: Metabolic syndrome has been identified as one of the most significant threats to human health in the 21st century. Exercise training has been shown to counteract obesity and metabolic syndrome. The present study aimed to investigate the effects of moderate exercise training on pancreatic beta-cell function and autonomic nervous system (ANS activity in rats fed a high-fat diet (HFD. Methods: Weaning rats were divided into four groups: rats fed a standard chow or HFD (sedentary, Control-SED and HFD-SED; or exercised, Control-EXE and HFD-EXE, respectively. Exercised rats ran (from 21- to 91-days-old for 60 minutes (3 times/week over a 10-week period. Glucose and insulin tolerance tests were performed. Pancreatic islets were isolated to study glucose-induced insulin secretion (GIIS. Parasympathetic and sympathetic nerve electrical signals were measured, and liver samples were processed and histologically analyzed. Results: Exercise prevented obesity, insulin resistance, and liver steatosis as well as improved total cholesterol, ALT, and AST levels. Islets from HFD rats showed insulin hypersecretion which was ameliorated by exercise. Exercise decreased vagal nerve activity in the HFD-EXE group and increased the activity of the sympathetic nervous system in both exercised groups. Conclusion: Exercise prevents obesity and liver steatosis and restores pancreatic beta-cell function and ANS activity in HFD-obese rats.

  11. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

    Science.gov (United States)

    Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

    2016-01-15

    Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease. PMID:26564715

  12. The Growth of Brown Adipose Tissue in Cold-acclimatized Rats after Depletion of Mast Cell Histamine by Compound 48/80

    Directory of Open Access Journals (Sweden)

    Daló Nelson L

    1998-01-01

    Full Text Available Cold acclimatization (4-5°C is accompanied by 2-3 fold increase of brown adipose tissue (BAT. This rapid growth of interscapular BAT was studied after histamine depletion. In control rats maintained at room temperature (28 ± 2°C the BAT histamine content was 23.4 ± 5.9 (mean ± SD µg/g of tissue and cold acclimatization (5±1°C produced a significant increase of BAT weight, but reduced the histamine content to 8.4 ± 1.9 µg/g. The total weight of BAT after 20 days of acclimatization was unaffected by depletion of histamine due to compound 48/80. The low level of histamine in BAT of cold acclimatized rats could be due to a fast rate of amine utilization; alternatively an altered synthesis or storage process may occur during acclimatization.

  13. Theaflavin Synthesized in a Selective, Domino-Type, One-Pot Enzymatic Biotransformation Method with Camellia sinensis Cell Culture Inhibits Weight Gain and Fat Accumulation to High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Takemoto, Masumi; Takemoto, Hiroaki; Saijo, Ryoyasu

    2016-08-01

    The polyphenolic compound theaflavin, which is the main red pigment present in black tea, is reported to elicit various physiological effects. Because of the extremely low concentration of theaflavin present in black tea, its extraction from black tea leaves in quantities sufficient for use in medical studies has been difficult. We have developed a simple, inexpensive, selective, domino-type, one-pot enzymatic biotransformation method for the synthesis of theaflavin that is suitable for use in medical studies. Subsequent administration of this synthetic theaflavin to high-fat diet-induced obese mice inhibited both body weight gain and visceral fat accumulation, with no significant difference in the amount of faeces between the experimental and control mice. PMID:27237789

  14. A case of prominent epicardial fat mimicking a tumor on echocardiography.

    OpenAIRE

    Ahn, Y. K.; Park, J. C.; Park, W S; Kim, N H; J.W. Kim; Kim, S H; Cho, J. H.; Jeong, M H; Cho, J. G.; Kang, J. C.

    1999-01-01

    Epicardial fat may anteriorly produce an echo-free space that can be mistaken for pericardial fluid. We recently experienced a 67-year-old woman with prominent epicardial fat which was presented as an echogenic tumor-like mass. She underwent open pericardiostomy to relieve large amount of pericardial effusion. Operative findings revealed only prominent epicardial fat. Biopsy of the pericardial and fat tissues revealed an inflammation and normal fat cells without any malignant cell infiltration.

  15. Seasonal food habits of brown bear (Ursus arctos syriacus Linnaeus, 1758 in Cenral Alborz Protected Area

    Directory of Open Access Journals (Sweden)

    Bagher Nezami Balouchi

    2014-11-01

    Full Text Available Mountains of Central Alborz Protected Area hold a big population of brown bear, the largest varnivore species in Iran. Understanding food habits is crucial to understanding the ecology of the species. Diet influences many ecological and life-history traits, such as spatial distribution, social and foraging behavior, body mass and reproduction. Therefore, during Jun 2006 to May 2007 we had a comprehensive study on brown bear food habits, as the largest omnivorous of the country in Central Alborz Protected Area. Our investigation showed that plant materials composed the main proportion of food items of the brown bears in the spring until mid-summer. Insects, especially ants were predominantly eaten in the first half of summer. As approaching to hibernation period in late autumn, fruits played the main role of bear food items having high fat content. We never witnessed bear attack on wild herbivores. Furthermore, we never found remains of wild herbivores except a few livestock remains in brown bear scats during our survey period. Accordingly, we concluded that brown bears were almost herbivorous in the Central Alborz Protected Area. We never found any bear scats or fresh signs in three consecutive years, between first of December until mid of March. Also, no direct sighting of brown bear was reported to us by local people and game keepers within the mentioned period. Accordingly, it can be concluded that the brown bears hibernate for a period of 3-3.5 months in winter in the Central Alborz Protected Area.

  16. Natural killer T cells and non-alcoholic fatty liver disease: Fat chews on the immune system

    Institute of Scientific and Technical Information of China (English)

    Michael Kremer; Ian N Hines

    2008-01-01

    Natural killer T cells (NKT) are an important subset of T lymphocytes. They are unique in their ability to produce both T helper 1 and T helper 2 associated cytokines, thus being capable of steering the immune system into either inflammation or tolerance. Disruption of NKT cell numbers or function results in severe deficits in immune surveillance against pathogens and tumor cells. Growing experimental evidence suggests that hepatosteatosis may reduce resident hepatic as well as peripheral NICE cells. Those models of hepatosteatosis and the change in NKT cell numbers are associated with a disruption of cytokine homeostasis, resulting in a more pronounced release of proinflammatory cytokines which renders the steatotic liver highly susceptible to secondary insults. In this letter to the editor, we focus on recently published data in the World Journal of Gastroenterology by Xu and colleagues demonstrating reduced peripheral NKT ceils in patients with non-alcoholic fatty liver disease, compare those findings with ours and others in different animal models of hepatosteatosis, and hypothesize about the potential underlying mechanism.

  17. Precursor cells from Atlantic salmon (Salmo salar visceral fat holds the plasticity to differentiate into the osteogenic lineage

    Directory of Open Access Journals (Sweden)

    Elisabeth Ytteborg

    2015-07-01

    Full Text Available In order to study the potential plasticity of Atlantic salmon (Salmo salar precursor cells (aSPCs from the adipogenic mesenchyme cell lineage to differentiate to the osteogenic lineage, aSPCs were isolated and cultivated under either osteogenic or adipogenic promoting conditions. The results strengthen the hypothesis that aSPCs most likely are predestined to the adipogenic lineage, but they also hold the flexibility to turn into other lineages given the right stimuli. This assumption is supported by the fact that the transcription factor pparγ , important for regulation of adiopogenesis, was silent in aSPCs grown in osteogenic media, while runx2, important for osteogenic differentiation, was not expressed in aSPCs cultivated in adipogenic media. After 2 weeks in osteogenic promoting conditions the cells started to deposit extracellular matrix and after 4 weeks, the cells started mineralizing secreted matrix. Microarray analyses revealed large-scale transcriptome responses to osteogenic medium after 2 days, changes remained stable at day 15 and decreased by magnitude at day 30. Induction was observed in many genes involved in osteogenic differentiation, growth factors, regulators of development, transporters and production of extracellular matrix. Transcriptome profile in differentiating adipocytes was markedly different from differentiating osteoblasts with far fewer genes changing activity. The number of regulated genes slowly increased at the mature stage, when adipocytes increased in size and accumulated lipids. This is the first report on in vitro differentiation of aSPCs from Atlantic salmon to mineralizing osteogenic cells. This cell model system provides a new valuable tool for studying osteoblastogenesis in fish.

  18. Unequivocal Identification of Brown Adipose Tissue in a Human Infant

    OpenAIRE

    Hu, Houchun H.; Tovar, Jason; Pavlova, Zdena; Smith, Michelle L; Gilsanz, Vicente

    2011-01-01

    We report the unique depiction of brown adipose tissue (BAT) by MRI and computed tomography (CT) in a human three month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and X-ray attenuation values in the latter. While numerous BAT imaging experiments...

  19. Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas

    OpenAIRE

    Toru Furukawa; Hitomi Sakamoto; Shoko Takeuchi; Mitra Ameri; Yuko Kuboki; Toshiyuki Yamamoto; Takashi Hatori; Masakazu Yamamoto; Masanori Sugiyama; Nobuyuki Ohike; Hiroshi Yamaguchi; Michio Shimizu; Noriyuki Shibata; Kyoko Shimizu; Keiko Shiratori

    2015-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we ide...

  20. Characterization of Human Knee and Chin Adipose-Derived Stromal Cells

    Directory of Open Access Journals (Sweden)

    Magali Kouidhi

    2015-01-01

    Full Text Available Animal study findings have revealed that individual fat depots are not functionally equivalent and have different embryonic origins depending on the anatomic location. Mouse bone regeneration studies have also shown that it is essential to match the Hox code of transplanted cells and host tissues to achieve correct repair. However, subcutaneous fat depots from any donor site are often used in autologous fat grafting. Our study was thus carried out to determine the embryonic origins of human facial (chin and limb (knee fat depots and whether they had similar features and molecular matching patterns. Paired chin and knee fat depots were harvested from 11 subjects and gene expression profiles were determined by DNA microarray analyses. Adipose-derived stromal cells (ASCs from both sites were isolated and analyzed for their capacity to proliferate, form clones, and differentiate. Chin and knee fat depots expressed a different HOX code and could have different embryonic origins. ASCs displayed a different phenotype, with chin-ASCs having the potential to differentiate into brown-like adipocytes, whereas knee-ASCs differentiated into white adipocytes. These results highlighted different features for these two fat sites and indicated that donor site selection might be an important factor to be considered when applying adipose tissue in cell-based therapies.

  1. C.elegans fat-1基因对SGC7901细胞的促凋亡作用%Effects of Gene Transfer of C. Elegana fat - 1 on the Growth and apoptosis of Human Gastric Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    马志国; 蒋正尧

    2008-01-01

    目的 通过在人胃癌SGC7901细胞系上转入外源C.elegans fat-1基因观其对细胞增殖或对调亡的影响.方法 构建携带有能够编码n-3多聚饱和脂肪酸脱氢酶的小秀丽隐杆线虫fat-1基因的重组质粒,转染人胃癌细胞SGC7901,检测n-6/n-3脂肪酸的比例,观察胃癌细胞的增殖和凋亡情况.结果 转染成功后携带有fat-1基因的胃癌细胞,显示了对于n-3脂肪酸饱和酶的高表达.脂类分析表明,n-6PUFAs的比例大幅度降低,n-3PUFAs水平明显提高,n-6/n-3脂肪酸比例,从10.45下降到了0.79,尤其是花生四烯酸和二十碳戊烯酸的比率.相应地,在表达有fat-1基因的胃癌细胞中,来源于n-6PUFAs的类花生酸含量有显著减少.同时,fat-1基因的转移导致大量胃癌细胞的凋亡,抑制胃癌细胞的增殖.结论 n-3脂肪酸去饱和酶的基因转移,能够有效调整人肿瘤细胞n-6/n-3脂肪酸的比例,起到抗癌作用.证明在癌症的预防和治疗中,n-6与n-3脂肪酸的比例扮演着一个重要的角色.

  2. Perception of fatness

    OpenAIRE

    Jałkiewicz, Małgorzata

    1997-01-01

    The study’s objective was to find out whether there is a relationship between bodily fatness traits described with anthropometric measurements and the assessment of the physical attractiveness of people with different degree of fat deposition. Furthermore, an attempt was made to answer the question whether we perceive the physique of another man as a whole or if we pay more attention to certain parts of the body and whether there is a stereotype of desirable fat deposition.

  3. 糖皮质激素对高脂饮食肥胖大鼠棕色脂肪和骨骼肌PGC-1αmRNA表达的影响%Effect of glucocorticoid on the expression of PGC-1α mRNA in brown adipose tissue and skeletal muscle of obese rats fed with high-fat diet

    Institute of Scientific and Technical Information of China (English)

    胡小磊; 石建华; 项平; 范艳萍; 苗艳君; 黄咏齐

    2009-01-01

    实时荧光定量PCR方法检测大鼠棕色脂肪和骨骼肌中PPARγ辅激活因子1α(PGC-1α)mRNA的表达.肥胖大鼠棕色脂肪和骨骼肌中PGC-1α mRNA表达水平低于普通大鼠(均P<0.01);应用高剂量糖皮质激素后普通大鼠和肥胖大鼠棕色脂肪和骨骼肌中PGC-1α mRNA表达水平降低.%Real-time fluorescent quantitative PCR was used to examine PGC-1α mRNA expression in brown adipose tissue and skeletal muscle of rats. The results showed that the expression levels of PGC-1α mRNA in brown adipose tissue and skeletal muscle of obese rats were lower than those of the normal ones (all P<0.01). After high dose glucocorticoid treatment, the levels of PGC-1α mRNA expression in brown adipose tissue and skeletal muscle, both in normal and obese rats, were decreased significantly.

  4. Brown adipose tissue in cetacean blubber.

    Science.gov (United States)

    Hashimoto, Osamu; Ohtsuki, Hirofumi; Kakizaki, Takehiko; Amou, Kento; Sato, Ryo; Doi, Satoru; Kobayashi, Sara; Matsuda, Ayaka; Sugiyama, Makoto; Funaba, Masayuki; Matsuishi, Takashi; Terasawa, Fumio; Shindo, Junji; Endo, Hideki

    2015-01-01

    Brown adipose tissue (BAT) plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1), within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT) scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool waters during

  5. Brown adipose tissue in cetacean blubber.

    Directory of Open Access Journals (Sweden)

    Osamu Hashimoto

    Full Text Available Brown adipose tissue (BAT plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1, within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool

  6. A Fat strange Repeller

    Institute of Scientific and Technical Information of China (English)

    申影; 何阅; 姜玉梅; 何大韧

    2004-01-01

    This article reports an observation on a fat strange repeller, which appears after a characteristic crisis observed in a kicked rotor subjected to a piecewise continuous force field. The discontinuity border in the definition range of the two-dimensional mapping, which describes the system, oscillates as the discrete time develops. At a threshold of a control parameter a fat chaotic attractor suddenly transfers to a fat transient set. The strange repeller, which appears after the crisis, is also a fat fractal. This is the reason why super-transience happens

  7. Mature ovarian teratoma with large floating fat globules

    Energy Technology Data Exchange (ETDEWEB)

    Son, Hye Min; Kim, See Hyung; Hwang, Il Seon [Keimyung University School of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of)

    2016-04-15

    Mature ovarian teratoma (dermoid cyst), a germ cell neoplasm, is one of the most common ovarian tumors. It is composed of derivatives of three germ cell layers. A mature ovarian teratoma with intracystic fat globules is rare. The pathogenesis on the formation of fat globules is unclear. Here we present a pathologically proven cystic ovarian teratoma with three large floating fat globules in a young woman with CT and MR findings.

  8. Thermoneutrality decreases thermogenic program and promotes adiposity in high-fat diet-fed mice.

    Science.gov (United States)

    Cui, Xin; Nguyen, Ngoc Ly T; Zarebidaki, Eleen; Cao, Qiang; Li, Fenfen; Zha, Lin; Bartness, Timothy; Shi, Hang; Xue, Bingzhong

    2016-05-01

    Brown/beige adipocytes are therapeutic targets to combat obesity due to their abilities to dissipate energy through adaptive thermogenesis. Most studies investigating induction of brown/beige adipocytes were conducted in cold condition (e.g., 4°C); much is unknown about how the thermogenic program of brown/beige adipocytes is regulated in thermoneutral condition (e.g., 30°C), which is within the thermal comfort zone of human dwellings in daily life. Therefore, this study aims to characterize the thermogenic program of brown/beige adipocytes in mice housed under ambient (22°C) versus thermoneutral condition (30°C). Male mice raised at 22°C or 30°C were fed either chow diet or high-fat (HF) diet for 20 weeks. Despite less food intake, chow-fed mice housed at 30°C remained the same body weight compared to mice at 22°C. However, these thermoneutrally housed mice displayed a decrease in the expression of thermogenic program in both brown and white fat depots with larger adipocytes. When pair-fed with chow diet, thermoneutrally housed mice showed an increase in body weight. Moreover, thermoneutrality increased body weight of mice fed with HF diet. This was associated with decreased expression of the thermogenic program in both brown and white fat depots of the thermoneutrally housed mice. The downregulation of the thermogenic program might have resulted from decreased sympathetic drive in the thermoneutrally housed mice evident by decreased expression of tyrosine hydroxylase expression and norepinephrine turnover in both brown and white fat depots. Our data demonstrate that thermoneutrality may negatively regulate the thermogenic program and sympathetic drive, leading to increased adiposity in mice.

  9. Moringa oleifera Lam. seed extract prevents fat diet induced oxidative stress in mice and protects liver cell-nuclei from hydroxyl radical mediated damage.

    Science.gov (United States)

    Das, Nilanjan; Ganguli, Debdutta; Dey, Sanjit

    2015-12-01

    High fat diet (HFD) prompts metabolic pattern inducing reactive oxygen species (ROS) production in mitochondria thereby triggering multitude of chronic disorders in human. Antioxidants from plant sources may be an imperative remedy against this disorder. However, it requires scientific validation. In this study, we explored if (i) Moringa oleifera seed extract (MoSE) can neutralize ROS generated in HFD fed mice; (ii) protect cell-nuclei damage developed by Fenton reaction in vitro. Swiss mice were fed with HFD to develop oxidative stress model (HFD group). Other groups were control, seed extract alone treated, and MoSE simultaneously (HS) treated. Treatment period was of 15 days. Antioxidant enzymes with tissue nitrite content (TNC) and lipid peroxidation (LPO) were estimated from liver homogenate. HS group showed significantly higher (P group. Further, TNC and LPO decreased significantly (P group compared to HFD fed group. MoSE also protected hepatocytes nuclei from the hydroxyl radicals generated by Fenton reaction. MoSE was found to be polyphenol rich with potent reducing power, free radicals and hydroxyl radicals scavenging activity. Thus, MoSE exhibited robust antioxidant prospective to neutralize ROS developed in HFD fed mice and also protected the nuclei damage from hydroxyl radicals. Hence, it can be used as herbal medication against HFD induced ROS mediated disorders.

  10. Moringa oleifera Lam. seed extract prevents fat diet induced oxidative stress in mice and protects liver cell-nuclei from hydroxyl radical mediated damage.

    Science.gov (United States)

    Das, Nilanjan; Ganguli, Debdutta; Dey, Sanjit

    2015-12-01

    High fat diet (HFD) prompts metabolic pattern inducing reactive oxygen species (ROS) production in mitochondria thereby triggering multitude of chronic disorders in human. Antioxidants from plant sources may be an imperative remedy against this disorder. However, it requires scientific validation. In this study, we explored if (i) Moringa oleifera seed extract (MoSE) can neutralize ROS generated in HFD fed mice; (ii) protect cell-nuclei damage developed by Fenton reaction in vitro. Swiss mice were fed with HFD to develop oxidative stress model (HFD group). Other groups were control, seed extract alone treated, and MoSE simultaneously (HS) treated. Treatment period was of 15 days. Antioxidant enzymes with tissue nitrite content (TNC) and lipid peroxidation (LPO) were estimated from liver homogenate. HS group showed significantly higher (P antioxidant power (FRAP) compared to only HFD fed group. Further, TNC and LPO decreased significantly (P antioxidant prospective to neutralize ROS developed in HFD fed mice and also protected the nuclei damage from hydroxyl radicals. Hence, it can be used as herbal medication against HFD induced ROS mediated disorders. PMID:26742324

  11. Hydrophobic organic chemicals (HOCs) removal from biologically treated landfill leachate by powder-activated carbon (PAC), granular-activated carbon (GAC) and biomimetic fat cell (BFC).

    Science.gov (United States)

    Liyan, Song; Youcai, Zhao; Weimin, Sun; Ziyang, Lou

    2009-04-30

    Biological pretreatment efficiently remove organic matter from landfill leachate, but further removal of refractory hydrophobic organic chemicals (HOCs) is hard even with advanced treatment. In this work, three-stage-aged refuse bioreactor (ARB) efficiently removed chemical oxygen demand (COD) and biochemical oxygen demand (BOD) of fresh leachate produced in Shanghai laogang landfill, from 8603 to 451 mg L(-1) and 1368 to 30 mg L(-1), respectively. In downstream treatment, 3 g L(-1) powder-activated carbon (PAC), granular-activated carbon (GAC) and biomimetic fat cell (BFC) removed 89.2, 73.4 and 81.1% HOCs, but only 24.6, 19.1 and 8.9% COD, respectively. Through the specific HOCs accumulation characteristics of BFC, about 11.2% HOCs with low molecular weight (BFC. It was also found that the biologically treated leachate effluent exhibited a wide molecular weight distribution (34-514,646 Da). These constitutes are derived from both autochthonous and allochthonous matters as well as biological activities.

  12. Soluble HMGB1 is a novel adipokine stimulating IL-6 secretion through RAGE receptor in SW872 preadipocyte cell line: contribution to chronic inflammation in fat tissue.

    Directory of Open Access Journals (Sweden)

    Brice Nativel

    Full Text Available Low-grade inflammation (LGI is a central phenomenon in the genesis of obesity and insulin-resistance characterized by IL-6 in human serum. Whereas this LGI was initially thought to be mainly attributed to macrophage activation, it is now known that pre-adipocytes and adipocytes secrete several adipokines including IL-6 and participate to LGI and associated pathologies. In macrophages, HMGB1 is a nuclear yet secreted protein and acts as a cytokine to drive the production of inflammatory molecules through RAGE and TLR2/4. In this paper we tested the secretion of HMGB1 and the auto- and paracrine contribution to fat inflammation using the human preadipocyte cell line SW872 as a model. We showed that 1 human SW872 secreted actively HMGB1, 2 IL-6 production was positively linked to high levels of secreted HMGB1, 3 recombinant HMGB1 boosted IL-6 expression and this effect was mediated by the receptor RAGE and did not involve TLR2 or TLR4. These results suggest that HMGB1 is a major adipokine contributing to LGI implementation and maintenance, and can be considered as a target to develop news therapeutics in LGI associated pathologies such as obesity and type II diabetes.

  13. The adipocyte clock controls brown adipogenesis through the TGF-Beta and BMP signaling pathways

    Science.gov (United States)

    The molecular clock is intimately linked to metabolic regulation, and brown adipose tissue plays a key role in energy homeostasis. However, whether the cell-intrinsic clock machinery participates in brown adipocyte development is unknown. Here, we show that Bmal1 (also known as ARNTL), the essential...

  14. Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte.

    Science.gov (United States)

    Rajan, Sujith; Shankar, Kripa; Beg, Muheeb; Varshney, Salil; Gupta, Abhishek; Srivastava, Ankita; Kumar, Durgesh; Mishra, Raj K; Hussain, Zakir; Gayen, Jiaur R; Gaikwad, Anil N

    2016-09-01

    The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics. CI treatment decreased expression of brown adipocyte-specific markers (such as PRDM16, PGC1α, and UCP1) and mitochondrial content as well as activity. CI-treated brown adipocytes showed drastic decrease in oxygen consumption rate (OCR) and spare respiratory capacity. Morphological study indicates increased accumulation of lipid droplets in CI-treated brown adipocytes. We have further validated these findings in vivo in C57BL/6 mice implanted with mini-osmotic insulin pump for 8weeks. CI treatment in mice leads to increased body weight gain, fat mass and impaired glucose intolerance with reduced energy expenditure and insulin sensitivity. CI-treated mice showed decreased BAT characteristics and function. We also observed increased inflammation and ER stress markers in BAT of CI-treated animals. The above results conclude that hyperinsulinemia has deleterious effect on brown adipocyte function, making it susceptible to insulin resistance. Thus, the above findings have greater implication in designing approaches for the treatment of insulin resistance and diabetes via recruitment of brown adipocytes. PMID:27340034

  15. Boron uptake, localization, and speciation in marine brown algae.

    Science.gov (United States)

    Miller, Eric P; Wu, Youxian; Carrano, Carl J

    2016-02-01

    In contrast to the generally boron-poor terrestrial environment, the concentration of boron in the marine environment is relatively high (0.4 mM) and while there has been extensive interest in its use as a surrogate of pH in paleoclimate studies in the context of climate change-related questions, the relatively depth independent, and the generally non-nutrient-like concentration profile of this element have led to boron being neglected as a potentially biologically relevant element in the ocean. Among the marine plant-like organisms the brown algae (Phaeophyta) are one of only five lineages of photosynthetic eukaryotes to have evolved complex multicellularity. Many of unusual and often unique features of brown algae are attributable to this singular evolutionary history. These adaptations are a reflection of the marine coastal environment which brown algae dominate in terms of biomass. Consequently, brown algae are of fundamental importance to oceanic ecology, geochemistry, and coastal industry. Our results indicate that boron is taken up by a facilitated diffusion mechanism against a considerable concentration gradient. Furthermore, in both Ectocarpus and Macrocystis some boron is most likely bound to cell wall constituent alginate and the photoassimilate mannitol located in sieve cells. Herein, we describe boron uptake, speciation, localization and possible biological function in two species of brown algae, Macrocystis pyrifera and Ectocarpus siliculosus. PMID:26679972

  16. Two types of brown adipose tissue in humans.

    Science.gov (United States)

    Lidell, Martin E; Betz, Matthias J; Enerbäck, Sven

    2014-01-01

    During the last years the existence of metabolically active brown adipose tissue in adult humans has been widely accepted by the research community. Its unique ability to dissipate chemical energy stored in triglycerides as heat makes it an attractive target for new drugs against obesity and its related diseases. Hence the tissue is now subject to intense research, the hypothesis being that an expansion and/or activation of the tissue is associated with a healthy metabolic phenotype. Animal studies provide evidence for the existence of at least two types of brown adipocytes. Apart from the classical brown adipocyte that is found primarily in the interscapular region where it constitutes a thermogenic organ, a second type of brown adipocyte, the so-called beige adipocyte, can appear within white adipose tissue depots. The fact that the two cell types develop from different precursors suggests that they might be recruited and stimulated by different cues and therefore represent two distinct targets for therapeutic intervention. The aim of this commentary is to discuss recent work addressing the question whether also humans possess two types of brown adipocytes and to highlight some issues when looking for molecular markers for such cells.

  17. The intake of high-fat diets induces an obesogenic-like gene expression profile in peripheral blood mononuclear cells, which is reverted by dieting.

    Science.gov (United States)

    Reynés, Bàrbara; García-Ruiz, Estefanía; Palou, Andreu; Oliver, Paula

    2016-06-01

    Peripheral blood mononuclear cells (PBMC) are increasingly used for nutrigenomic studies. In this study, we aimed to identify whether these cells could reflect the development of an obesogenic profile associated with the intake of high-fat (HF) diets. We analysed, by real-time RT-PCR, the dietary response of key genes related to lipid metabolism, obesity and inflammation in PBMC of control rats, rats fed a cafeteria or a commercial HF diet and rats fed a control diet after the intake of a cafeteria diet (post-cafeteria model). Cafeteria diet intake, which resulted in important overweight and related complications, altered the expressions of most of the studied genes in PBMC, evidencing the development of an obesogenic profile. Commercial HF diet, which produced metabolic alterations but in the absence of noticeably increased body weight, also altered PBMC gene expression, inducing a similar regulatory pattern as that observed for the cafeteria diet. Regulation of carnitine palmitoyltransferase I (Cpt1a) mRNA expression was of special interest; its expression reflected metabolic alterations related to the intake of both obesogenic diets (independently of increased body weight) even at an early stage as well as metabolic recovery in post-cafeteria animals. Thus, PBMC constitute an important source of biomarkers that reflect the increased adiposity and metabolic deregulation associated with the intake of HF diets. In particular, we propose an analysis of Cpt1a expression as a good biomarker to detect the early metabolic alterations caused by the consumption of hyperlipidic diets, and also as a marker of metabolic recovery associated to weight loss. PMID:27080153

  18. Tuberose sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma

    International Nuclear Information System (INIS)

    AIM: To study the radiological characteristics of renal masses in individuals with tuberous sclerosis complex (TSC) using serial CT, and to examine how renal cell carcinoma (RCC) may be differentiated from indeterminate cysts or masses. METHODS: This was a retrospective study of 12 cases of TSC in which dedicated renal CT followed after US had demonstrated cystic or sonographically unusual renal masses. The CT density of all masses was measured and the masses categorized as simple cysts, complex cysts, angiomyolipomas or indeterminate solid masses. Subjects were maintained on regular follow-up with repeat CT or MRI and interval renal US. Indeterminate masses that showed rapid growth were considered suspicious for renal cell carcinoma and biopsy or nephrectomy followed. RESULTS: Comparative data were available for a median of 4 years. In each case the renal masses were multiple and bilateral; mean mass diameter was 3.6 cm. Among a total of 206 masses, 18 were simple cysts and 3 were complex cysts. Of the complex cysts, 1 proved to be an angiomyolipoma on histology and the other 2 showed no growth. Of the solid masses, 133 were typical angiomyolipomas (AMLs) and 52 were indeterminate. On follow-up, only 3 indeterminate masses showed rapid growth (>0.5 cm/year), of which only 1 proved to be an RCC on biopsy. The other 2 were minimal-fat AMLs, and the remainder of the masses showed no or slow growth. CONCLUSION: Many renal masses associated with TSC are radiologically indeterminate. A growth threshold of >0.5 cm/year identified the only RCC in this study (0.5% of all masses). Yearly radiological follow-up of indeterminate renal masses is recommended for individuals with TSC

  19. Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet

    Directory of Open Access Journals (Sweden)

    Juan Andrés Orellana

    2014-12-01

    Full Text Available Nicotine, the most important neuroteratogen of tobacco smoke, can reproduce brain and cognitive disturbances per se when administered prenatally. However, it is still unknown if paracrine signaling among brain cells participates in prenatal nicotine-induced brain impairment of adult offspring. Paracrine signaling is partly mediated by unopposed channels formed by connexins (hemichannels and pannexins serving as aqueous pores permeable to ions and small signaling molecules, allowing exchange between the intra- and extracellular milieus. Our aim was to address whether prenatal nicotine exposure changes the activity of those channels in adult mice offspring under control conditions or subjected to a second challenge during young ages: high-fat/cholesterol (HFC diet. To induce prenatal exposure to nicotine, osmotic minipumps were implanted in CF1 pregnant mice at gestational day 5 to deliver nicotine bitartrate or saline (control solutions. After weaning, offspring of nicotine-treated or untreated pregnant mice were fed ad libitum with chow or HFC diets for 8 weeks. The functional state of Cx43 and Panx1 unopposed channels was evaluated by dye uptake experiments in hippocampal slices from 11-week-old mice. We found that prenatal nicotine increased the opening of Cx43 hemichannels in astrocytes, and Panx1 channels in microglia and neurons only if offspring mice were fed with HFC diet. Blockade of iNOS, COX2 and EP1, P2X7 and NMDA receptors, showed differential inhibition of prenatal nicotine-induced channel opening in glial cells and neurons. Importantly, inhibition of the above mentioned enzymes and receptors, or blockade of Cx43 and Panx1 unopposed channels greatly reduced ATP and glutamate release from hippocampal slices of prenatally nicotine-exposed offspring. We propose that unregulated gliotransmitter release through Cx43 and Panx1 unopposed channels may participate in brain alterations observed in offspring of mothers exposed to tobacco smoke

  20. Metabolic activity of brown, "beige," and white adipose tissues in response to chronic adrenergic stimulation in male mice.

    Science.gov (United States)

    Labbé, Sébastien M; Caron, Alexandre; Chechi, Kanta; Laplante, Mathieu; Lecomte, Roger; Richard, Denis

    2016-07-01

    Classical brown adipocytes such as those found in interscapular brown adipose tissue (iBAT) represent energy-burning cells, which have been postulated to play a pivotal role in energy metabolism. Brown adipocytes can also be found in white adipose tissue (WAT) depots [e.g., inguinal WAT (iWAT)] following adrenergic stimulation, and they have been referred to as "beige" adipocytes. Whether the presence of these adipocytes, which gives iWAT a beige appearance, can confer a white depot with some thermogenic activity remains to be seen. In consequence, we designed the present study to investigate the metabolic activity of iBAT, iWAT, and epididymal white depots in mice. Mice were either 1) kept at thermoneutrality (30°C), 2) kept at 30°C and treated daily for 14 days with an adrenergic agonist [CL-316,243 (CL)], or 3) housed at 10°C for 14 days. Metabolic activity was assessed using positron emission tomography imaging with fluoro-[(18)F]deoxyglucose (glucose uptake), fluoro-[(18)F]thiaheptadecanoic acid (fatty acid uptake), and [(11)C]acetate (oxidative activity). In each group, substrate uptakes and oxidative activity were measured in anesthetized mice in response to acute CL. Our results revealed iBAT as a major site of metabolic activity, which exhibited enhanced glucose and nonesterified fatty acid uptakes and oxidative activity in response to chronic cold and CL. On the other hand, beige adipose tissue failed to exhibit appreciable increase in oxidative activity in response to chronic cold and CL. Altogether, our results suggest that the contribution of beige fat to acute-CL-induced metabolic activity is low compared with that of iBAT, even after sustained adrenergic stimulation.

  1. Dietary fat and carcinogenesis

    NARCIS (Netherlands)

    Woutersen, R.A.; Appel, M.J.; Garderen-Hoetmer, A. van; Wijnands, M.V.W.

    1999-01-01

    Epidemiologic investigations have suggested a relationship between dietary fat intake and various types of cancer incidences. Furthermore, epidemiologic studies as well as studies with animal models have demonstrated that not only the amount but also the type of fat consumed is important. At present

  2. Learning about Fats

    Science.gov (United States)

    ... eat a mix of foods — some with higher percentages of fat and some with lower percentages — so that you ... and they insulate nervous system tissue in the body. So fat is not the enemy, but you'll want ...

  3. Upregulation of p-Smad2 contributes to FAT10-induced oncogenic activities in glioma.

    Science.gov (United States)

    Dai, Bin; Zhang, Yisong; Zhang, Peng; Pan, Changcun; Xu, Cheng; Wan, Weiqing; Wu, Zhen; Zhang, Junting; Zhang, Liwei

    2016-07-01

    The human leukocyte antigen f-associated transcript 10 (FAT10) has a similar structure and function with ubiquitin, which efficiently mediate proteasome degradation in an ubiquitin-independent manner. FAT10 expression is upregulated in many tumor tissues and plays a vital role in cell cycle regulation and tumor genesis. However, its role in glioma has not been illuminated. The aim of this study was to evaluate the prognostic value of FAT10 and investigate its functional roles in glioma. The expression of FAT10 in glioma patient samples was examined using quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry methods. Glioma cell lines with either FAT10 overexpression or knockdown were created. The effect of FAT10 on glioma cell migration and invasion was investigated using these cells. In the present study, we had shown that FAT10 was elevated significantly in glioma samples and correlated with tumor pathological grade. FAT10 high-expression glioma is associated with a poor clinical prognosis. Overexpression of FAT10 promoted proliferation, invasion, migration, and sphere formation of glioma cells, whereas downregulation of FAT10 had an opposite effect. Overexpression of FAT10 also promoted the growth of glioma cells in vivo. Moreover, FAT10 enhanced the phosphorylation of Smad2, which contributes to FAT10-induced oncogenic activities in glioma. In conclusion, these findings indicate that FAT10 is a critical regulator potential therapeutic target of glioma. PMID:26733179

  4. Age-related rump fat, fat percent, body fat mass, leptin, androgens and semen parameters ofArab stallions

    Institute of Scientific and Technical Information of China (English)

    AmalMAboEl-Maaty; GamalA ElSisy; MonaHShaker; OmimaH Ezzo

    2014-01-01

    Objectives:To study the effect of age and body fat on leptin levels and semen parameters of Arab horse.Methods:Fifteen fertileArab stallions of different ages belonging toPoliceAcademy were divided into three equal groups according to their age.Old horses are those of >18 yeas (18-27),Mid-age horses≥13 to18 years(13-18),Young horses are those of <12 years(7-11). Semen was evaluated three times for each stallion.Blood and seminal plasma were assayed for measuring leptin, testosterone and estradiol.Subcutaneous rump fat thickness was measured using ultrasound for estimating body fat percent and fat mass percent.Results:All body fat parameters were significantly high inYoung stallions and decreased with increasing age.As age increased, testosterone levels increases but leptin levels decreased.Age was inversely correlated with fat%, fat mass and leptin.All fat parameters had direct correlation with leptin in semen and serum but an inverse one with serum testosterone.Serum leptin directly correlated with sperm cell concentration inMid- age stallions and inversely correlated with percent of live sperm in Old stallions.Semen leptin correlated directly with both percent of live sperm and percent of abnormal sperm inOld stallions.Conclusion:This study proved that aging in stallions is related to a drop in fertility, a decrease in body fat and in turn leptin.Arab stallions of age7 to18 years could be used in the breeding efficiently.

  5. Differential fat harvesting

    Directory of Open Access Journals (Sweden)

    Sebastian Torres Farr

    2014-12-01

    Full Text Available Aim: Volume replacement with fillers is regularly performed with the use of diverse volumetric materials to correct different structures around the face, depending on the volume enhancement required and the thickness of the soft tissue envelope. Differential fat harvesting and posterior grafting is performed to place the correct fat parcel size for each target area, expanding the potential applications of fat. Methods: Sixty patients consecutively recruited on a first come basis undergone a facial fat grafting procedure, in private practice setting between March 2012 and October 2013. Fat grafting quantity and quality was predicted for each case. Differential harvesting was performed, with 2 fat parcels size. Processing was performed through washing. Fat infiltration was carried out through small cannulas or needles depending on the treated area. Outcomes were analysed both by the physicians and the patients at 7 days, 1 month, 3 months and 6 months through a perceived satisfaction questionnaire. Parameters considered were downtime or discomfort, skin benefits, volume restoration, reabsorption rate estimated and overall improvement. Results: Full facial differential fat grafting procedure lasted an average of 1.5-2.5 h. Average downtime was 3-4 days. Follow-up was performed to a minimum of 6 months. Both patient and physician overall satisfaction rates were mostly excellent. Adverse events like lumps or irregularities were not encountered. Conclusion: Differential fat harvesting and posterior grafting is a valid alternative, to expand the repertoire of fat use, allow a more homogeneous effect, reduce the potential complications, speed up the process, improve graft survival, and to enhance overall aesthetic outcome.

  6. Brown Adipose Tissue: A New Target for Antiobesity Therapy

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2010-08-01

    Full Text Available BACKGROUND: Human fat consist of white and brown adipose tissue (WAT and BAT. Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. CONTENT: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT imaging, immunohistochemistry and gene and protein expression assays to prove conclusively that adult humans have functional BAT. BAT is important for thermogenesis and energy balance in small mammals and its induction in mice promotes energy expenditure, reduces adiposity and protects mice from diet-induced obesity. The thermogenic capacity of BAT is impressive. In humans, it has been estimated that as little as 50g of BAT could utilize up to 20% of basal caloric needs if maximally stimulated. SUMMARY: The obesity pandemic requires new and novel treatments. The past few years have witnessed multiple studies conclusively showing that adult humans have functional BAT, a tissue that has a tremendous capacity for obesity-reducing thermogenesis. Novel therapies targeting BAT thermogenesis may be available in the near future as therapeutic options for obesity and diabetes. Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity. KEYWORDS: brown adipose tissue, thermogenesis, energy expenditure, antiobesity therapy.

  7. Free fatty acids and IL-6 induce adipocyte galectin-3 which is increased in white and brown adipose tissues of obese mice.

    Science.gov (United States)

    Krautbauer, Sabrina; Eisinger, Kristina; Hader, Yvonne; Buechler, Christa

    2014-10-01

    Galectin-3 regulates immune cell function and clearance of advanced glycation end products. Galectin-3 is increased in serum of obese humans and mice and most studies suggest that this protein protects from inflammation in metabolic diseases. Current data show that galectin-3 is markedly elevated in the liver, subcutaneous and intra-abdominal fat depots of mice fed a high fat diet and ob/ob mice. Galectin-3 is also increased in brown adipose tissues of these animals and immunohistochemistry confirms higher levels in adipocytes. Raised galectin-3 in obese white adipocytes has been described in the literature and regulation of adipocyte galectin-3 by metabolites with a role in obesity has been analyzed. Galectin-3 is expressed in 3T3-L1 fibroblasts and human preadipocytes and is modestly induced in mature adipocytes. In 3T3-L1 adipocytes galectin-3 is localized in the cytoplasm and is also detected in cell supernatants. Glucose does not alter soluble galectin-3. Lipopolysaccharide has no effect while TNF reduces and IL-6 raises this lectin in cell supernatants. Palmitate and oleate modestly elevate soluble galectin-3. Differentiation of 3T3-L1 cells in the presence of 100 μM and 200 μM linoleate induces soluble galectin-3 and cellular levels are upregulated by the higher concentration. Current data suggest that free fatty acids and IL-6 increase galectin-3 in adipocytes and thereby may contribute to higher levels in obesity.

  8. Permeabilization of enterocytes induced by absorption of dietary fat

    DEFF Research Database (Denmark)

    Danielsen, Erik Michael; Hansen, Gert H; Rasmussen, Karina;

    2013-01-01

    Absorption of dietary fat in the small intestine involves epithelial exposure to potentially harmful molecules such as bile salts and free fatty acids. We used organ culture of porcine jejunal explants incubated with a pre-digested mixture of fat (plant oil), bile and pancreatin to mimick...... the physiological process of dietary fat absorption, and short exposures to the fat mixture caused fat droplet accumulation within villus enterocytes. Lucifer yellow (LY), a fluorescent membrane-impermeable polar tracer was included to monitor epithelial integrity. Both in controls and during fat absorption LY...... penetrated the epithelium and accumulated in the basal lamina and the lamina propria. LY was also seen in the paracellular space, whereas villus enterocytes were generally only weakly labeled except for small amounts taken up by apical endocytosis. In the crypts, however, fat absorption induced cell...

  9. MR-based assessment of body fat distribution and characteristics.

    Science.gov (United States)

    Baum, Thomas; Cordes, Christian; Dieckmeyer, Michael; Ruschke, Stefan; Franz, Daniela; Hauner, Hans; Kirschke, Jan S; Karampinos, Dimitrios C

    2016-08-01

    The assessment of body fat distribution and characteristics using magnetic resonance (MR) methods has recently gained significant attention as it further extends our pathophysiological understanding of diseases including obesity, metabolic syndrome, or type 2 diabetes mellitus, and allows more detailed insights into treatment response and effects of lifestyle interventions. Therefore, the purpose of this study was to review the current literature on MR-based assessment of body fat distribution and characteristics. PubMed search was performed to identify relevant studies on the assessment of body fat distribution and characteristics using MR methods. T1-, T2-weighted MR Imaging (MRI), Magnetic Resonance Spectroscopy (MRS), and chemical shift-encoding based water-fat MRI have been successfully used for the assessment of body fat distribution and characteristics. The relationship of insulin resistance and serum lipids with abdominal adipose tissue (i.e. subcutaneous and visceral adipose tissue), liver, muscle, and bone marrow fat content have been extensively investigated and may help to understand the underlying pathophysiological mechanisms and the multifaceted obese phenotype. MR methods have also been used to monitor changes of body fat distribution and characteristics after interventions (e.g. diet or physical activity) and revealed distinct, adipose tissue-specific properties. Lastly, chemical shift-encoding based water-fat MRI can detect brown adipose tissue which is currently the focus of intense research as a potential treatment target for obesity. In conclusion, MR methods reliably allow the assessment of body fat distribution and characteristics. Irrespective of the promising findings based on these MR methods the clinical usefulness remains to be established.

  10. PPAR{alpha} does not suppress muscle-associated gene expression in brown adipocytes but does influence expression of factors that fingerprint the brown adipocyte

    Energy Technology Data Exchange (ETDEWEB)

    Walden, Tomas B.; Petrovic, Natasa [The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm (Sweden); Nedergaard, Jan, E-mail: jan@metabol.su.se [The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm (Sweden)

    2010-06-25

    Brown adipocytes and myocytes develop from a common adipomyocyte precursor. PPAR{alpha} is a nuclear receptor important for lipid and glucose metabolism. It has been suggested that in brown adipose tissue, PPAR{alpha} represses the expression of muscle-associated genes, in this way potentially acting to determine cell fate in brown adipocytes. To further understand the possible role of PPAR{alpha} in these processes, we measured expression of muscle-associated genes in brown adipose tissue and brown adipocytes from PPAR{alpha}-ablated mice, including structural genes (Mylpf, Tpm2, Myl3 and MyHC), regulatory genes (myogenin, Myf5 and MyoD) and a myomir (miR-206). However, in our hands, the expression of these genes was not influenced by the presence or absence of PPAR{alpha}, nor by the PPAR{alpha} activator Wy-14,643. Similarly, the expression of genes common for mature brown adipocyte and myocytes (Tbx15, Meox2) were not affected. However, the brown adipocyte-specific regulatory genes Zic1, Lhx8 and Prdm16 were affected by PPAR{alpha}. Thus, it would not seem that PPAR{alpha} represses muscle-associated genes, but PPAR{alpha} may still play a role in the regulation of the bifurcation of the adipomyocyte precursor into a brown adipocyte or myocyte phenotype.

  11. Role of developmental transcription factors in white, brown and beige adipose tissues.

    Science.gov (United States)

    Hilton, Catriona; Karpe, Fredrik; Pinnick, Katherine E

    2015-05-01

    In this review we discuss the role of developmental transcription factors in adipose tissue biology with a focus on how these developmental genes may contribute to regional variation in adipose tissue distribution and function. Regional, depot-specific, differences in lipid handling and signalling (lipolysis, lipid storage and adipokine/lipokine signalling) are important determinants of metabolic health. At a cellular level, preadipocytes removed from their original depot and cultured in vitro retain depot-specific functional properties, implying that these are intrinsic to the cells and not a function of their environment in situ. High throughput screening has identified a number of developmental transcription factors involved in embryological development, including members of the Homeobox and T-Box gene families, that are strongly differentially expressed between regional white adipose tissue depots and also between brown and white adipose tissue. However, the significance of depot-specific developmental signatures remains unclear. Developmental transcription factors determine body patterning during embryogenesis. The divergent developmental origins of regional adipose tissue depots may explain their differing functional characteristics. There is evidence from human genetics that developmental genes determine adipose tissue distribution: in GWAS studies a number of developmental genes have been identified as being correlated with anthropometric measures of adiposity and fat distribution. Additionally, compelling functional studies have recently implicated developmental genes in both white adipogenesis and the so-called 'browning' of white adipose tissue. Understanding the genetic and developmental pathways in adipose tissue may help uncover novel ways to intervene with the function of adipose tissue in order to promote health.

  12. De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development.

    Science.gov (United States)

    Alvarez-Dominguez, Juan R; Bai, Zhiqiang; Xu, Dan; Yuan, Bingbing; Lo, Kinyui Alice; Yoon, Myeong Jin; Lim, Yen Ching; Knoll, Marko; Slavov, Nikolai; Chen, Shuai; Chen, Peng; Lodish, Harvey F; Sun, Lei

    2015-05-01

    Brown adipose tissue (BAT) protects against obesity by promoting energy expenditure via uncoupled respiration. To uncover BAT-specific long non-coding RNAs (lncRNAs), we used RNA-seq to reconstruct de novo transcriptomes of mouse brown, inguinal white, and epididymal white fat and identified ∼1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPARγ, C/EBPα, and C/EBPβ. One of them, lnc-BATE1, is required for establishment and maintenance of BAT identity and thermogenic capacity. lnc-BATE1 inhibition impairs concurrent activation of brown fat and repression of white fat genes and is partially rescued by exogenous lnc-BATE1 with mutated siRNA-targeting sites, demonstrating a function in trans. We show that lnc-BATE1 binds heterogeneous nuclear ribonucleoprotein U and that both are required for brown adipogenesis. Our work provides an annotated catalog for the study of fat depot-selective lncRNAs and establishes lnc-BATE1 as a regulator of BAT development and physiology.

  13. The rotation of brown dwarfs

    CERN Document Server

    Scholz, Aleks

    2016-01-01

    One of the characteristic features of low-mass stars is their propensity to shed large amounts of angular momentum throughout their evolution. This distinguishs them from brown dwarfs which remain fast rotators over timescales of gigayears. Brown dwarfs with rotation periods longer than a couple of days have only been found in star forming regions and young clusters. This is a useful constraint on the mass dependency of mechanisms for angular momentum regular in stars. Rotational braking by disks and winds become highly inefficient in the substellar regime. In this short review I discuss the observational evidence for the fast rotation in brown dwarfs, the implications, and the link to the spin-mass relation in planets.

  14. Identification of Fat4 as a candidate tumor suppressor gene in breast cancers

    OpenAIRE

    Qi, Chao; Zhu, Yiwei Tony; Hu, Liping; Zhu, Yi-Jun

    2009-01-01

    Fat, a candidate tumor suppressor in drosophila, is a component of Hippo signaling pathway involved in controlling organ size. We found that a ~3Mbp deletion in mouse chromosome 3 caused tumorigenesis of a non-tumorigenic mammary epithelial cell line. The expression of Fat4 gene, one member of the Fat family, in the deleted region was inactivated, which resulted from promoter methylation of another Fat4 allele following the deletion of one Fat4 allele. Re-expression of Fat4 in Fat4-deficient ...

  15. Detection of prion infectivity in fat tissues of scrapie-infected mice.

    Directory of Open Access Journals (Sweden)

    Brent Race

    2008-12-01

    Full Text Available Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection.

  16. Effects of ethyl acetate extract of Kaempferia parviflora on brown adipose tissue.

    Science.gov (United States)

    Kobayashi, Hiroko; Horiguchi-Babamoto, Emi; Suzuki, Mio; Makihara, Hiroko; Tomozawa, Hiroshi; Tsubata, Masahito; Shimada, Tsutomu; Sugiyama, Kiyoshi; Aburada, Masaki

    2016-01-01

    We have previously reported the effects of Kaempferia parviflora (KP), including anti-obesity, preventing various metabolic diseases, and regulating differentiation of white adipose cells. In this study we used Tsumura, Suzuki, Obese Diabetes (TSOD) mice--an animal model of spontaneous obese type II diabetes--and primary brown preadipocytes to examine the effects of the ethyl acetate extract of KP (KPE) on brown adipose tissue, which is one of the energy expenditure organs. TSOD mice were fed with MF mixed with either KPE 0.3 or 1% for 8 weeks. Computed tomography images showed that whitening of brown adipocytes was suppressed in the interscapular tissue of the KPE group. We also examined mRNA expression of uncoupling protein 1 (UCP-1) and β3-adrenalin receptor (β3AR) in brown adipose tissue. As a result, mRNA expression of UCP-1 significantly increased in the KPE 1% treatment group, indicating that KPE activated brown adipose tissue. We then evaluated the direct effects of KPE on brown adipocytes using primary brown preadipocytes isolated from interscapular brown adipocytes in ICR mice. Triacylglycerol (TG) accumulation in primary brown preadipocytes was increased by KPE in a dose-dependent manner. Each mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), UCP-1, and β3AR exhibited an upward trend compared with the control group. Moreover, some polymethoxyflavonoids (PMFs), the main compound in KP, also increased TG accumulation. This study therefore showed that KPE enhanced the thermogenesis effect of brown adipocytes as well as promoted the differentiation of brown adipocyte cells. PMID:26386971

  17. Live-trapping and handling brown bear

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This paper reports techniques developed to live trap and handle brown bears on the Kodiak National Wildlife Refuge. The brown bears (Ursus middendorffi) on the...

  18. Browns Park NWR Water Use Report- 1999

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report contains locations and water use at Browns Park NWR for 1999. A basic introduction highlighting the region that Browns Park NWR is a part of and the...

  19. Browns Park NWR Water Use Report- 2000

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report contains locations and water use at Browns Park NWR for 2000. A basic introduction highlighting the region that Browns Park NWR is a part of and the...

  20. Advances in Insulin Resistance Fat Cell Secretion Factors%与胰岛素抵抗相关脂肪细胞分泌因子的研究进展