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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...... in brown adipocyte 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...

  4. Histochemical study of brown-fat cells in the golden hamster (Mesocricetus auratus) in cultures

    International Nuclear Information System (INIS)

    The authors undertake the task of studying the synthesis of certain hormones by brown-fat cells. The authors used brown-fat cells from the golden hamster. The metabolism of brown-fat cells was studied on precultured cells, which made it possible to detect the synthesis of the studied substances rather than their accumulation in the organ. The authors conducted three experiments. First, fragments of brown fat were cultivated in diffusion chambers in vivo. Pieces of brown fat were cultivated in parallel in vitro on agar (organotypic cultures) and on plasma (histotypic cultures). During cultivation in diffusion chambers, the chambers were implanted in the abdominal cavity of young white rats. For in vitro cultivation, TCM 199 plus 15-20% calf serum was used. A total of 36 cultures with 12 cultures in each series of experiments were performed. The auto-radiographic studies of brown-fat cells were conducted on 24-hour cultures and on brown-fat fragments taken from the intact animal. The cultures were incubated with isotopes for 1 h. Either [3H]lysine (87.3 Ci/mM specific activity), [3H]arginine (16.7 Ci/mM), [3H]glycerol (43 Ci/mM), or [3H]cholesterol (43 Ci/mM) were added to the medium. After incubation, the cultures were washed three times in pure medium, fixed in Sierra fluid, and embedded in paraffin. The paraffin sections were covered with Ilford K2 emulsion, and the preparations were exposed for 20 days at 40C temperature. Radio-immunological methods were used to study the accumulation of estradiol-17-beta in the culture medium by the Dobson method and that of testerone. The culture medium was taken on cultivation days 2,4,6,8, and 10. The medium was changed during cultivation every third day, which made it possible to judge the rates of accumulation of material with increase in the cultivation times

  5. 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...

  6. 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...

  7. 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.

  8. Brown Fat Paucity Due to Impaired BMP Signaling Induces Compensatory Browning of White Fat

    OpenAIRE

    Schulz, Tim J.; Huang, Ping; Huang, Tian Lian; Xue, Ruidan; McDougall, Lindsay E.; Townsend, Kristy L.; Cypess, Aaron M.; Mishina, Yuji; Gussoni, Emanuela; Tseng, Yu-Hua

    2013-01-01

    Summary Maintenance of body temperature is essential for survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation 1 . Due to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans 2-5 , BAT holds great promise for the treatment of obesity and metabolic syndrome 1 . Rodent data suggest the existence of two types of brown fat cells: the constitutive BAT (cBAT), which is of embryonic origin and...

  9. Brown Fat Paucity Due to Impaired BMP Signaling Induces Compensatory Browning of White Fat

    OpenAIRE

    Schulz, Tim J.; Huang, Ping; Huang, Tian Lian; Xue, Ruidan; McDougall, Lindsay E.; Townsend, Kristy L.; Cypess, Aaron M.; Mishina, Yuji; Gussoni, Emanuela; Tseng, Yu-Hua

    2013-01-01

    Summary Maintenance of body temperature is essential for survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation1. Due to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans2-5, BAT holds great promise for the treatment of obesity and metabolic syndrome1. Rodent data suggest the existence of two types of brown fat cells: the constitutive BAT (cBAT), which is of embryonic origin and anato...

  10. 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

  11. 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......, there was no difference in UCP1, PGC-1α, PRDM16, suggesting both depots had equal brown fat potency. Taken together, supraclavicular brown fat derived from adult humans seems to represent a type of brown fat with distinct features from both subcutaneous white/brite and interscapular brown fat. Therefore...

  12. Dietary fat overload reprograms brown fat mitochondria

    OpenAIRE

    Lettieri Barbato, Daniele; Tatulli, Giuseppe; Vegliante, Rolando; Cannata, Stefano M.; Bernardini, Sergio; Ciriolo, Maria R.; Aquilano, Katia

    2015-01-01

    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 stron...

  13. 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...

  14. Brown fat and vascular heat dissipation

    OpenAIRE

    Warner, Amy; Mittag, Jens

    2014-01-01

    Current efforts to treat obesity and associated disorders focus on the stimulation of energy expenditure by increasing thermogenesis, for instance through activating brown adipose tissue or more recently “beige” or “brite” fat, a relatively novel type of adipose tissue with putative thermogenic potential. In this commentary, we aim to provide an alternative perspective on the current trend of analyzing and manipulating thermogenesis, brought about by our recent publication, in which we invest...

  15. 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.

  16. The brown fat secretome: metabolic functions beyond thermogenesis

    OpenAIRE

    Wang, Guo-Xiao; Zhao, Xu-Yun; Lin, Jiandie D.

    2015-01-01

    Brown fat is highly active in fuel oxidation and dissipates chemical energy through uncoupling protein 1 (UCP1)-mediated heat production. Activation of brown fat leads to increased energy expenditure, reduced adiposity, and lower plasma glucose and lipid levels, thus contributing to better homeostasis. Uncoupled respiration and thermogenesis have been considered to be responsible for the metabolic benefits of brown adipose tissue. Recent studies have demonstrated that brown adipocytes also se...

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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 ...

  1. 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

  2. Characterization of a primary brown adipocyte culture system derived from human fetal interscapular fat

    OpenAIRE

    Seiler, Sarah E.; Xu, Dan; Ho, Jia-Pei; Lo, Kinyui Alice; Buehrer, Benjamin M; Ludlow, Y John W; Kovalik, Jean-Paul; Sun, Lei

    2015-01-01

    Brown fat has gained widespread attention as a potential therapeutic target to treat obesity and associated metabolic disorders. Indeed, the anti-obesity potential of multiple targets to stimulate both brown adipocyte differentiation and recruitment have been verified in rodent models. However, their therapeutic potential in humans is unknown due to the lack of a human primary brown adipocyte cell culture system. Likewise, the lack of a well-characterized human model has limited the discovery...

  3. 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.

  4. Ouabain-sensitive component of brown fat thermogenesis.

    Science.gov (United States)

    Horwitz, B. A.

    1973-01-01

    The study discussed was undertaken to quantify the amount of energy utilized by the ouabain-sensitive Na(+)-K(+) membrane pump during the norepinephrine-induced thermogenesis of brown adipose tissue. The data obtained indicate that the observed inhibition of the catecholamine-induced increase in brown fat thermogenesis by ouabain does not reflect an inhibition of cyclic AMP synthesis.

  5. Can Brown Fat Win the Battle Against White Fat?

    Science.gov (United States)

    Elattar, Sawsan; Satyanarayana, Ande

    2015-10-01

    A rapid growth in the overweight and obese population in the last few decades suggest that the current diet, exercise, awareness or drug strategies are still not effectively restraining the obesity epidemic. Obesity results from increased energy intake, and the body's energy balance shifts towards energy abundance. Therefore, current research is focused on developing new strategies aimed at increasing energy expenditure. As a result, brown adipose tissue (BAT) is receiving tremendous attention since the major function of BAT is to dissipate energy as heat. For example, mouse models that have increased BAT activity or increased numbers of brown-like adipocytes within the white adipose tissue (WAT) are lean and protected from obesity. Alternatively, mouse models that lack BAT activity are more susceptible to age and diet-induced obesity. However, a significant loss of BAT mass during the natural growth process in humans has created enormous challenges in effectively utilizing this tissue to increase energy expenditure. New strategies are primarily focused on expanding the BAT mass and/or activating the existing BAT. In this regard, recent finding that expression of early B cell factor-2 (Ebf2) reprograms the white pre-adipocytes into brown adipocytes is a significant break-through in developing BAT-mediated strategies to treat obesity. Here we review the major biological functions of WAT and BAT, which play critical but opposing roles in the energy spectrum, energy storage versus energy expenditure, and we evaluate whether activation and/or expansion of BAT is practically achievable to treat obesity in humans. PMID:25760392

  6. 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...

  7. 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 ...

  8. Human brown fat and obesity: methodological aspects

    OpenAIRE

    WouterDavidVan Marken Lichtenbelt

    2011-01-01

    Much is known about brown adipose tissue in rodents. Its function is to generate heat in response to low environmental temperatures and to diet or overfeeding. The knowledge about BAT in humans is still rather limited despite the recent rediscovery of its functionality in adults. This review highlights the information available on the contribution of BAT in increasing human energy expenditure in relation to obesity. Besides that methodological aspects will be discussed that need special atten...

  9. Human Brown Fat and Obesity: Methodological Aspects

    OpenAIRE

    van Marken Lichtenbelt, Wouter

    2011-01-01

    Much is known about brown adipose tissue (BAT) in rodents. Its function is to generate heat in response to low environmental temperatures and to diet or overfeeding. The knowledge about BAT in humans is still rather limited despite the recent rediscovery of its functionality in adults. This review highlights the information available on the contribution of BAT in increasing human energy expenditure in relation to obesity. Besides that methodological aspects will be discussed that need special...

  10. 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

    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....

  11. Human brown fat and obesity: methodological aspects

    Directory of Open Access Journals (Sweden)

    WouterDavidVan Marken Lichtenbelt

    2011-10-01

    Full Text Available Much is known about brown adipose tissue in rodents. Its function is to generate heat in response to low environmental temperatures and to diet or overfeeding. The knowledge about BAT in humans is still rather limited despite the recent rediscovery of its functionality in adults. This review highlights the information available on the contribution of BAT in increasing human energy expenditure in relation to obesity. Besides that methodological aspects will be discussed that need special attention in order to unravel the heat producing capacity of human BAT, the recruitment of the tissue and its functionality.

  12. 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

  13. 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

  14. 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...

  15. Ablation of NG2 proteoglycan leads to deficits in brown fat function and to adult onset obesity.

    Directory of Open Access Journals (Sweden)

    Yunchao Chang

    Full Text Available Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O(2 consumption and CO(2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16 and peroxisome proliferator-activated receptor γ coactivator (PGC1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes.

  16. 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...

  17. 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

    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...... increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise....

  18. MicroRNA-378 controls classical brown fat expansion to counteract obesity

    OpenAIRE

    Pan, Dongning; Mao, Chunxiao; Quattrochi, Brian; Friedline, Randall H.; Zhu, Lihua J.; Jung, Dae Young; Kim, Jason K.; Lewis, Brian; Wang, Yong-Xu

    2014-01-01

    Both classical brown adipocytes and brown-like beige adipocytes are considered as promising therapeutic targets for obesity; however, their development, relative importance, and functional coordination are not well understood. Here we show that a modest expression of miR-378/378* in adipose tissue specifically increases classical brown fat (BAT) mass, but not white fat (WAT) mass. Remarkably, BAT expansion, rather than miR-378 per se, suppresses formation of beige adipocytes in subcutaneous W...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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...

  1. Duodenal Lipid Sensing Activates Vagal Afferents to Regulate Non-Shivering Brown Fat Thermogenesis in Rats

    OpenAIRE

    Blouet, Clémence; Schwartz, Gary J.

    2012-01-01

    Previous evidence indicates that duodenal lipid sensing engages gut-brain neurocircuits to determine food intake and hepatic glucose production, but a potential role for gut-brain communication in the control of energy expenditure remains to be determined. Here, we tested the hypothesis that duodenal lipid sensing activates a gut–brain–brown adipose tissue neuraxis to regulate thermogenesis. We demonstrate that direct administration of lipids into the duodenum increases brown fat temperature....

  2. Systemic control of brown fat thermogenesis: integration of peripheral and central signals

    OpenAIRE

    Schulz, Tim J.; Tseng, Yu-Hua

    2013-01-01

    Brown adipose tissue (BAT) is of great scientific interest as a potential target to treat obesity. The development of novel strategies to quantify brown fat thermogenesis in adult humans now enables minimally invasive assessment of novel pharmacotherapeutics. Input from the central nervous system (CNS) via sympathetic efferents is widely regarded as the key controller of BAT-mediated thermogenesis in response to changes in body temperature or nutrient availability. More recently, however, it ...

  3. 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.

  4. 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

  5. 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

  6. Brown Fat and the Myth of Diet-Induced Thermogenesis

    OpenAIRE

    Kozak, Leslie P.

    2010-01-01

    The notion that brown adipose tissue (BAT) in mice or humans maintains energy balance by burning off excess calories seems incompatible with evolutionary biology. Studies in obese rats and mice lacking UCP1 indicate that diet-induced thermogenesis by BAT is unlikely.

  7. 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....

  8. 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 ...

  9. 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...

  10. Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis.

    Science.gov (United States)

    Hoeke, Geerte; Kooijman, Sander; Boon, Mariëtte R; Rensen, Patrick C N; Berbée, Jimmy F P

    2016-01-01

    Atherosclerosis, for which hyperlipidemia is a major risk factor, is the leading cause of morbidity and mortality in Western society, and new therapeutic strategies are highly warranted. Brown adipose tissue (BAT) is metabolically active in human adults. Although positron emission tomography-computed tomography using a glucose tracer is the golden standard to visualize and quantify the volume and activity of BAT, it has become clear that activated BAT combusts fatty acids rather than glucose. Here, we review the role of brown and beige adipocytes in lipoprotein metabolism and atherosclerosis, with evidence derived from both animal and human studies. On the basis of mainly data from animal models, we propose a model in which activated brown adipocytes use their intracellular triglyceride stores to generate fatty acids for combustion. BAT rapidly replenishes these stores by internalizing primarily lipoprotein triglyceride-derived fatty acids, generated by lipoprotein lipase-mediated hydrolysis of triglycerides, rather than by holoparticle uptake. As a consequence, BAT activation leads to the generation of lipoprotein remnants that are subsequently cleared via the liver provided that an intact apoE-low-density lipoprotein receptor pathway is present. Through these mechanisms, BAT activation reduces plasma triglyceride and cholesterol levels and attenuates diet-induced atherosclerosis development. Initial studies suggest that BAT activation in humans may also reduce triglyceride and cholesterol levels, but potential antiatherogenic effects should be assessed in future studies. PMID:26837747

  11. 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 ...

  12. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    Science.gov (United States)

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged. PMID:26041126

  13. Characterization of beta-adrenergic receptors and adenylate cyclase activity in rat brown fat

    International Nuclear Information System (INIS)

    Catecholamines stimulate thermogenesis in rat brown fat through a mechanism which involves binding to the beta-adrenergic receptor (BAR), stimulation of adenylate cyclase (AC) and culminating with uncoupling of mitochondrial respiration from ATP synthesis. The authors characterized BAR, AC and cytochrome (cyt) c oxidase in CDF (F-344) interscapular brown fat. Scatchard analysis of [125]Iodopindolol binding yields a straight line consistent with a single class of antagonist binding sites with 41.8 +/- 12.0 fmol BAR/mg protein and a K/sub d/ of 118 +/- 15 pM. Binding was both specific and stereospecific. Competition with 1-propranolol (K/sub d/ = 6.7 nM) was 15 times more potent than d-propranolol (K/sub d/ = 103 nM). Competition with isoproterenol (K/sub d/ = 79 nM) was 10 times more potent than epinephrine (K/sub d/ = 820 nM) which was 35 times more potent than norepinephrine (K/sub d/ = 2.9 x 10-5 M) suggesting predominate beta2-type BAR. Cyt c oxidase activity was assessed in brown fat mitochrondrial preparations. The ratio of BAR to cyt c activity was 959 +/- 275 nmol BAR/mol cyc c/min. Isoproterenol (0.1 mM) stimulated AC activity was 24 times GTP (0.1 mM) stimulated AC (98.5 vs 40.7 pmol cAMP/min/mg). NaF-stimulated AC was nine times basal activity (90.5 vs 11.3 pmol cAMP/min/mg). These data demonstrate the presence of a beta-2-type BAR coupled to adenylate cyclase in rat brown fat

  14. Characterization of beta-adrenergic receptors and adenylate cyclase activity in rat brown fat

    Energy Technology Data Exchange (ETDEWEB)

    Baresi, L.A.; Morley, J.E.; Scarpace, P.J.

    1986-03-01

    Catecholamines stimulate thermogenesis in rat brown fat through a mechanism which involves binding to the beta-adrenergic receptor (BAR), stimulation of adenylate cyclase (AC) and culminating with uncoupling of mitochondrial respiration from ATP synthesis. The authors characterized BAR, AC and cytochrome (cyt) c oxidase in CDF (F-344) interscapular brown fat. Scatchard analysis of (/sup 125/)Iodopindolol binding yields a straight line consistent with a single class of antagonist binding sites with 41.8 +/- 12.0 fmol BAR/mg protein and a K/sub d/ of 118 +/- 15 pM. Binding was both specific and stereospecific. Competition with 1-propranolol (K/sub d/ = 6.7 nM) was 15 times more potent than d-propranolol (K/sub d/ = 103 nM). Competition with isoproterenol (K/sub d/ = 79 nM) was 10 times more potent than epinephrine (K/sub d/ = 820 nM) which was 35 times more potent than norepinephrine (K/sub d/ = 2.9 x 10/sup -5/ M) suggesting predominate beta/sub 2/-type BAR. Cyt c oxidase activity was assessed in brown fat mitochrondrial preparations. The ratio of BAR to cyt c activity was 959 +/- 275 nmol BAR/mol cyc c/min. Isoproterenol (0.1 mM) stimulated AC activity was 24 times GTP (0.1 mM) stimulated AC (98.5 vs 40.7 pmol cAMP/min/mg). NaF-stimulated AC was nine times basal activity (90.5 vs 11.3 pmol cAMP/min/mg). These data demonstrate the presence of a beta-/sub 2/-type BAR coupled to adenylate cyclase in rat brown fat.

  15. 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.

  16. Genetic Manipulation of Brown Fat Via Oral Administration of an Engineered Recombinant Adeno-associated Viral Serotype Vector.

    Science.gov (United States)

    Huang, Wei; McMurphy, Travis; Liu, Xianglan; Wang, Chuansong; Cao, Lei

    2016-06-01

    Recombinant adeno-associated virus (rAAV) vectors are attractive vehicles for gene therapy. Gene delivery to the adipose tissue using naturally occurring AAV serotypes is less successful compared to liver and muscle. Here, we demonstrate that oral administration of an engineered serotype Rec2 led to preferential transduction of brown fat with absence of transduction in the gastrointestinal track. Among the six natural and engineered serotypes being compared, Rec2 was the most efficient serotype achieving high level transduction at a dose 1~2 orders lower than reported doses for systemic administration. Overexpressing vascular endothelial growth factor (VEGF) in brown fat via oral administration of Rec2-VEGF vector increased the brown fat mass and enhanced thermogenesis. In contrast, knockdown VEGF in brown fat of VEGF (loxP) mice via Rec2-Cre vector hampered cold response and decreased brown fat mass. Oral administration of Rec2 vector provides a novel tool to genetically manipulate brown fat for research and therapeutic applications. PMID:26857843

  17. 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

  18. Fat deposition and flesh quality in seawater reared, triploid brown trout (Salmo trutta) as affected by dietary fat levels and starvation

    OpenAIRE

    Regost, Christelle; Arzel, Jacqueline; Cardinal, Mireille; Laroche, M; Kaushik, Sadasivam

    2001-01-01

    Three isoproteic (crude protein content: 56%) diets with different fat levels (11%, 20%, and 26%) were fed to triplicate groups of triploid brown trout (initial average body weight of 1.5 kg), reared in seawater. At the end of 3 months of feeding, fish fed the high-fat (HF) diet were split into two groups: a triplicate group of fish received the low-fat diet and another triplicate group was kept unfed for a further 2-month period. Fish initially fed the low-fat diet during the first period we...

  19. 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

  20. 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

  1. 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...

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

    Science.gov (United States)

    Singhal, Vibha; Maffazioli, Giovana D.; Ackerman, Kate E.; Lee, Hang; Elia, Elisa F.; Woolley, Ryan; Kolodny, Gerald; Cypess, Aaron M.; Misra, Madhusmita

    2016-01-01

    Background 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. Purpose 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. Methods 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. Results 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. Conclusions Our study

  3. 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

  4. Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet

    OpenAIRE

    Chi H. L. Dinh; Alexander Szabo; Yinghua Yu; Danielle Camer; Qingsheng Zhang; Hongqin Wang; Xu-Feng Huang

    2015-01-01

    Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/B...

  5. Inherent Plasticity of Brown Adipogenesis in White Fat of Mice Allows for Recovery from Effects of Post-Natal Malnutrition

    OpenAIRE

    Kozak, Leslie P.; Koza, Robert A.; Anunciado-Koza, Rea; Mendoza, Tamra; Newman, Susan

    2012-01-01

    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 b...

  6. Can brown fat uptake of 18F-FDG be reduced by beta-blockers?

    International Nuclear Information System (INIS)

    With the increasing application of F-18-fluorodeoxyglucose (FDG) positron emission imaging, there has been an evolving appreciation for the range of normal variants and the realization that false- positives can lead to serious consequences. One of the most common causes of a false-positive study is the uptake of FDG in areas of brown adipose tissue. BAT is generally present in deep cervical regions, including the supraclavicular areas, the interscapular and paravertebral regions, and areas near large vessels. Areas of involvement are often spatially closely related to important lymph node groups in the neck, axilla, and upper mediastinum, making critical differentiation difficult. The uptake of 18F FDG in brown adipose tissue (BAT) limits the ability of a PET scan to detect the sites of viable disease. Many studies have been done after premedication with Diazepam (benzodiazepines) to reduce the uptake of FDG by brown fat. But they are of limited value. Thus, it would be ideal if a drug could completely reverse the brown fat uptake and thus aid in proper management of the patient. The aim of this study is to see if by giving a single dose of a beta-blocker such as 'Ciplar' (Propranolol) 40 mg, 30 minutes prior to the FDG injection will help in reduction of brown fat uptake of 18F-FDG or not. Materials and Methods: Patients who were referred for a PET scan, either for a pretreatment or a post treatment evaluation and who showed FDG uptake in brown adipose tissue (BAT) were taken up for this study. The total number of patients was 14. A repeat PET scan was done after a gap of at least 48 hrs after the first study. The patients were advised to keep themselves warm with adequate warm clothing on the day of the second study. 40 mg of 'Ciplar' (propranolol) was given orally 30 minutes prior to the 18F-FDG injection. A whole body PET scan was performed on a dedicated whole body PET scanner (ADVANCE, GE Medical Systems, Milwaukee, WI.), using attenuation correction with 68

  7. Reduction of the 18FDG uptake by the brown fat with the help of propranolol in a difficult case of lymphoma with residual disease suspicion

    International Nuclear Information System (INIS)

    The oncology group of the French Society of nuclear medicine implemented evaluation criteria of the lymphomas therapy response. The problem often encountered is this one of identification of minimum residual fixations in PET-F.D.G., considered as the residual disease in the non Hodgkin lymphomas. we report the case of a thirty four years old patient treated for diffuse at big B cells non Hodgkin lymphoma, in failure after the first line of treatment and with persistence of a hyper-metabolism in pre and post graft at the level of a para-cardiac residual mass. The post auto graft PET examination showed an important activation of the brown fat, able to question the origin of the residual para-cardiac hyper-metabolism in this dramatic situation, for a young patient and potentially still in therapy failure. In order to reduce the F.D.G. captation by the brown fat, it was proposed a new PET evaluation with propranolol administration (beta blocking) before the tracer injection. The intake of propranolol allowed to reduce in an important way, the F.D.G. captation by the brown fat, without modifying the residual hyper-metabolism. This result is going to lead to the realisation of a surgical biopsy. (N.C.)

  8. 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.

  9. 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

  10. 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 a ...... for C/EBP (an antimitotic protein), whereas Ccna1 expression (related to cell proliferation) was unchanged. Overall, our data strongly suggest that the cold-induced emergence of brown adipocytes in WAT predominantly reflects ß3-adrenoceptor-mediated transdifferentiation....

  11. Hypothalamic GLP-1: the control of BAT thermogenesis and browning of white fat

    OpenAIRE

    López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2015-01-01

    Brown adipose tissue (BAT) is a specialized organ responsible for thermogenesis, a process required for maintaining body temperature. Since the discovery that BAT and brite/beige cells are functional in adult humans, many studies have been focusing on the physiology and functionality of this organ. The brain is controlling the maintenance of body temperature through a complex neuronal network. One of the candidates to modulate thermogenesis at central level is glucagon-like peptide-1 (GLP-1),...

  12. 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.

  13. Brown fat distribution in the chest wall of infants - normal appearance, distribution and evolution on CT scans of the chest

    International Nuclear Information System (INIS)

    While reviewing chest CT scans of infants, we repeatedly observed hyperdense enhancing tissue in the chest wall that is not well described in radiology literature. This study was undertaken to describe the imaging features of this tissue in chest walls of infants. CT scans of the chest conducted on all infants between April 2008 and October 2009 were retrospectively reviewed. CT studies with any deviation from normal radiation or contrast dose or those with chest wall anatomical distortion were excluded. One hundred eighty-eight infants were scanned, with 202 MDCTs, of which 180 (89.1%) received contrast agent. Fifty-four of 180 (30%) cases revealed focal areas of hyperdensity in various locations. All positive cases ranged between 2 days and 9 months of age. The areas of distribution of hyperdensity had excellent correlation with known areas of brown fat in the chest wall, known from nuclear medicine studies, and hence we concluded these to represent the same. Brown fat in the chest wall can be seen as enhancing tissue on contrast CT scans done on infants. This is a normal morphological component with the brown fat converting to normal fat. It is important to recognize it in the chest wall of infants to avoid misinterpretation. (orig.)

  14. 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.

  15. Brown fat distribution in the chest wall of infants - normal appearance, distribution and evolution on CT scans of the chest

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Priya; Babyn, Paul S.; Shammas, Amer; Miller, Stephen F. [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada)

    2011-08-15

    While reviewing chest CT scans of infants, we repeatedly observed hyperdense enhancing tissue in the chest wall that is not well described in radiology literature. This study was undertaken to describe the imaging features of this tissue in chest walls of infants. CT scans of the chest conducted on all infants between April 2008 and October 2009 were retrospectively reviewed. CT studies with any deviation from normal radiation or contrast dose or those with chest wall anatomical distortion were excluded. One hundred eighty-eight infants were scanned, with 202 MDCTs, of which 180 (89.1%) received contrast agent. Fifty-four of 180 (30%) cases revealed focal areas of hyperdensity in various locations. All positive cases ranged between 2 days and 9 months of age. The areas of distribution of hyperdensity had excellent correlation with known areas of brown fat in the chest wall, known from nuclear medicine studies, and hence we concluded these to represent the same. Brown fat in the chest wall can be seen as enhancing tissue on contrast CT scans done on infants. This is a normal morphological component with the brown fat converting to normal fat. It is important to recognize it in the chest wall of infants to avoid misinterpretation. (orig.)

  16. Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet

    Science.gov (United States)

    Dinh, Chi H. L.; Szabo, Alexander; Yu, Yinghua; Camer, Danielle; Zhang, Qingsheng; Wang, Hongqin; Huang, Xu-Feng

    2015-01-01

    Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity. PMID:26066016

  17. Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Chi H. L. Dinh

    2015-06-01

    Full Text Available Obesity results in changes in brown adipose tissue (BAT morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7 of C57BL/6J mice were fed either a high-fat diet (HFD, a high-fat diet supplemented with BARD (HFD/BARD, or a low-fat diet (LFD for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM and dorsal vagal complex (DVC in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α. Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

  18. Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet.

    Science.gov (United States)

    Dinh, Chi H L; Szabo, Alexander; Yu, Yinghua; Camer, Danielle; Zhang, Qingsheng; Wang, Hongqin; Huang, Xu-Feng

    2015-06-01

    Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity. PMID:26066016

  19. 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

  20. 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...

  1. 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...

  2. 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...

  3. Direct evidence of brown adipocytes in different fat depots in children

    OpenAIRE

    Rockstroh, Denise; Landgraf, Kathrin; Wagner, Isabel Viola; Gesing, Julia; Tauscher, Roy; Lakowa, Nicole; Kiess, Wieland; Bühligen, Ulf; Wojan, Magdalena; Till, Holger; Blüher, Matthias; Körner, Antje

    2015-01-01

    Recent studies suggested the persistence of brown adipocytes in adult humans, as opposed to being exclusively present in infancy. In this study, we investigated the presence of brown-like adipocytes in adipose tissue (AT) samples of children and adolescents aged 0 to 18 years and evaluated the association with age, location, and obesity. For this, we analysed AT samples from 131 children and 23 adults by histological, immunohistochemical and expression analyses. We detected brown-like and UCP...

  4. 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

  5. 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

    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...... 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...

  6. Non-Invasive Quantification of White and Brown Adipose Tissues and Liver Fat Content by Computed Tomography in Mice

    OpenAIRE

    Lubura, Marko; Hesse, Deike; Neumann, Nancy; Scherneck, Stephan; Wiedmer, Petra; Schürmann, Annette

    2012-01-01

    Objectives Obesity and its distribution pattern are important factors for the prediction of the onset of diabetes in humans. Since several mouse models are suitable to study the pathophysiology of type 2 diabetes the aim was to validate a novel computed tomograph model (Aloka-Hitachi LCT-200) for the quantification of visceral, subcutaneous, brown and intrahepatic fat depots in mice. Methods Different lean and obese mouse models (C57BL/6, B6.V-Lepob, NZO) were used to determine the most adequ...

  7. Direct evidence of brown adipocytes in different fat depots in children.

    Directory of Open Access Journals (Sweden)

    Denise Rockstroh

    Full Text Available Recent studies suggested the persistence of brown adipocytes in adult humans, as opposed to being exclusively present in infancy. In this study, we investigated the presence of brown-like adipocytes in adipose tissue (AT samples of children and adolescents aged 0 to 18 years and evaluated the association with age, location, and obesity. For this, we analysed AT samples from 131 children and 23 adults by histological, immunohistochemical and expression analyses. We detected brown-like and UCP1 positive adipocytes in 10.3% of 87 lean children (aged 0.3 to 10.7 years and in one overweight infant, whereas we did not find brown adipocytes in obese children or adults. In our samples, the brown-like adipocytes were interspersed within white AT of perirenal, visceral and also subcutaneous depots. Samples with brown-like adipocytes showed an increased expression of UCP1 (>200fold, PRDM16 (2.8fold, PGC1α and CIDEA while other brown/beige selective markers, such as PAT2, P2RX5, ZIC1, LHX8, TMEM26, HOXC9 and TBX1 were not significantly different between UCP1 positive and negative samples. We identified a positive correlation between UCP1 and PRDM16 within UCP1 positive samples, but not with any other brown/beige marker. In addition, we observed significantly increased PRDM16 and PAT2 expression in subcutaneous and visceral AT samples with high UCP1 expression in adults. Our data indicate that brown-like adipocytes are present well beyond infancy in subcutaneous depots of non-obese children. The presence was not restricted to typical perirenal locations, but they were also interspersed within WAT of visceral and subcutaneous depots.

  8. 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...

  9. (11)C-meta-hydroxyephedrine PET/CT imaging allows in vivo study of adaptive thermogenesis and white-to-brown fat conversion

    OpenAIRE

    Quarta, C.; F. Lodi; Mazza, R; Giannone, F; Boschi, L.; Nanni, C; E. Nisoli; Boschi, S; Pasquali, R.; Fanti, S.; P. Iozzo; Pagotto, U.

    2013-01-01

    Several lines of evidence suggest that novel pharmacological approaches aimed at converting white adipose tissue (WAT) into brown adipose tissue (BAT) may represent an effective therapeutic strategy for obesity and related disorders. (18)F-fluorodeoxyglucose (18F-FDG) is the only positron emission tomography (PET) tracer commonly used to study BAT function, and so far no functional tools have been described to investigate in vivo white-to-brown fat conversion. In this report, we show that the...

  10. 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...

  11. 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

  12. 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.

  13. 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. PMID:26333689

  14. 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...

  15. 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

  16. 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.

  17. 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.

  18. 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....

  19. 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...

  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. 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

    the fat graft with adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We have reviewed original studies published on fat transplantation enriched with ASC. We found four murine and three human studies that investigated the subject after a sensitive search of publications. In...... the human studies, so-called cell assisted lipotransfer (CAL) increased the ASC concentration 2-5 times compared with non-manipulated fat grafts, which caused a questionable improvement in survival of fat grafts, compared with that of traditional lipofilling. In contrast, in two of the murine studies......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...

  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. Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats.

    Science.gov (United States)

    Zhang, Jun; Bai, Xiaozhi; Zhao, Bin; Wang, Yunchuan; Su, Linlin; Chang, Peng; Wang, Xujie; Han, Shichao; Gao, Jianxin; Hu, Xiaolong; Hu, Dahai; Liu, Xiaoyan

    2016-05-01

    Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 × 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection. PMID:26662284

  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. Do Stem Cells Have an Effect When We Fat Graft?

    Science.gov (United States)

    Rinker, Brian D; Vyas, Krishna S

    2016-06-01

    Fat grafting has become a widely accepted modality of soft tissue restoration and has found applications in many areas of aesthetic and reconstructive plastic surgery. Numerous claims have been made regarding the regenerative effects of fat grafting on the recipient bed. The purpose of this paper is to survey the available literature to answer the question of whether fat grafting has a positive effect on the surrounding tissues. It has been convincingly demonstrated that fat grafts contain viable adipose-derived stem cells (ASCs). The fate of these cells is determined by the microenvironment of the recipient bed, but animal studies have shown that a large fraction of ASCs survive engraftment. Numerous clinical studies have demonstrated the positive effects of fat grafting on recipient tissues. Improvement in validated scar scores as well as scar stiffness measurements have been documented after fat grafting of burn scars. Fat grafting has also been convincingly demonstrated to improve the quality of irradiated tissues, as measured by validated clinical scales and staged histology. It is ultimately unclear whether ASCs are responsible for these effects, but the circumstantial evidence is weighty. Fat grafting is effective for volumizing and improving skin quality in the setting of radiation, burns, and other scars. The observed effects are likely due to ASCs, but the evidence does not support the routine use of ASC-enriched fat grafts. PMID:26545225

  6. β-arrestin-1 contributes to brown fat function and directly interacts with PPARα and PPARγ.

    Science.gov (United States)

    Wang, Congcong; Zeng, Xianglu; Zhou, Zhaocai; Zhao, Jian; Pei, Gang

    2016-01-01

    The peroxisome proliferator-activated receptor (PPAR) family plays central roles in brown adipose tissue (BAT) adipogenesis and contributes to body temperature maintenance. The transcriptional activity of PPAR family has been shown to be tightly controlled by cellular signal networks. β-arrestins function as major secondary messengers of G protein-coupled receptors (GPCR) signaling by functional interactions with diverse proteins. Here, we report that β-arrestin-1 knock-out mice show enhanced cold tolerance. We found that β-arrestin-1 directly interacts with PPARα and PPARγ through a LXXXLXXXL motif, while D371 in PPARα and L311/N312/D380 in PPARγ are required for their interactions with β-arrestin-1. Further mechanistic studies showed that β-arrestin-1 promotes PPARα- but represses PPARγ-mediated transcriptional activities, providing potential regulatory pathway for BAT function. PMID:27301785

  7. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure.

    Science.gov (United States)

    Wu, Michelle V; Bikopoulos, George; Hung, Steven; Ceddia, Rolando B

    2014-12-01

    This study investigated the regulation of thermogenic capacity in classical brown adipose tissue (BAT) and subcutaneous inguinal (SC Ing) white adipose tissue (WAT) and how it affects whole-body energy expenditure in sedentary and endurance-trained rats fed ad libitum either low fat or high fat (HF) diets. Analysis of tissue mass, PGC-1α and UCP-1 content, the presence of multilocular adipocytes, and palmitate oxidation revealed that a HF diet increased the thermogenic capacity of the interscapular and aortic brown adipose tissues, whereas exercise markedly suppressed it. Conversely, exercise induced browning of the SC Ing WAT. This effect was attenuated by a HF diet. Endurance training neither affected skeletal muscle FNDC5 content nor circulating irisin, but it increased FNDC5 content in SC Ing WAT. This suggests that locally produced FNDC5 rather than circulating irisin mediated the exercise-induced browning effect on this fat tissue. Importantly, despite reducing the thermogenic capacity of classical BAT, exercise increased whole-body energy expenditure during the dark cycle. Therefore, browning of subcutaneous WAT likely exerted a compensatory effect and raised whole-body energy expenditure in endurance-trained rats. Based on these novel findings, we propose that exercise-induced browning of the subcutaneous WAT provides an alternative mechanism that reduces thermogenic capacity in core areas and increases it in peripheral body regions. This could allow the organism to adjust its metabolic rate to accommodate diet-induced thermogenesis while simultaneously coping with the stress of chronically increased heat production through exercise. PMID:25344623

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

    Energy Technology Data Exchange (ETDEWEB)

    Wu, S.Y.; Fisher, D.A.; Stern, J.S.; Glick, Z.

    1986-03-01

    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 T/sub 4/ to T/sub 3/ in BAT, through activity of T/sub 4/ 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 22/sup 0/C+/-2. Group 3 was fed rat chow and maintained at 8/sup 0/C+/-1 for 7 days. Activity of T/sub 4/5'deiodinase was determined in vitro. T/sub 3/ was measured by a radioimmunoassay. The rate of T/sub 4/ to T/sub 3/ 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 T/sub 3//scapular BAT depot, per hour). However, lean rats exposed to the cold displayed about a 5 fold increase in T/sub 4/5' deiodinase activity (p<0.0001), with only a small increase displayed by the cold exposed obese rats. Our data suggest that a reduced capacity of the brown rat to produce T/sub 3/ may account for the reduced tolerance of obese animals to cold, but it does not account for their reduced diet induced BAT thermogenesis.

  9. 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...

  10. 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.

  11. 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.

  12. Porosity at photo-induced fat cell lipolysis

    Science.gov (United States)

    Doubrovsky, V. A.; Yanina, I. Y.; Tuchin, V. V.

    2012-06-01

    The "specific structures" on the fat cells' membranes in vitro as a result of photodynamic treatment was registered. These structures were identified as cytoplasm/oil microdrops flowed out through the pores in the membranes. The impact of Brilliant Green dissolved in water-ethanol solutions and irradiation by a LED lamp on the quantity and size of "specific structures" on the membranes was investigated. It was demonstrated that optical selective action on fat cells sensitized by Brilliant Green led to the growth of "specific structures" (pores) number during the time interval after light exposure. A high degree of correlation between the optical clearing of fat tissue and quantity of "specific structures" (pores) was found. This result proves our early prediction about mechanism of light-induced fat cells' lipolysis via increased cell membrane porosity.

  13. 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

  14. Thermogenin amount and activity in hamster brown fat mitochondria: effect of cold acclimation

    Energy Technology Data Exchange (ETDEWEB)

    Sundin, U.; Moore, G.; Nedergaard, J.; Cannon, B.

    1987-05-01

    To investigate the acclimation process in a hibernator, four different parameters of thermogenin amount and activity were investigated in brown adipose tissue mitochondria from cold-exposed and cold-acclimated Syrian hamsters. Hamsters, which are hibernators, have been considered to be primed for thermogenesis and thus not to show cold-acclimation effects, but here a significant increase in (/sup 3/H)GDP-binding capacity was observed, and this increase was paralleled by an increase in thermogenin antigen amount, as measured in an enzyme-linked immunosorbent assay. The transient nature of the effect of cold exposure on (/sup 3/H)GDP binding, characteristically observed with rat mitochondria, was not observed with hamster mitochondria, and the increase in (/sup 3/H)GDP binding occurred without a change in the dissociation constant. The increase in thermogenin amount was paralleled by an increase both in GDP-sensitive Cl/sup -/ permeability of the mitochondria and in GDP-sensitive respiration. It was established that it is the maximal activity of thermogenin that is rate limiting for thermogenesis in isolated mitochondria, provided that an optimal substrate is used (such as palmitoyl carnitine). Cold acclimation also increased the total amount of mitochondria in the tissue, leading totally to a sixfold increase in thermogenin content of the hamster. It is concluded that hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation.

  15. Thermogenin amount and activity in hamster brown fat mitochondria: effect of cold acclimation

    International Nuclear Information System (INIS)

    To investigate the acclimation process in a hibernator, four different parameters of thermogenin amount and activity were investigated in brown adipose tissue mitochondria from cold-exposed and cold-acclimated Syrian hamsters. Hamsters, which are hibernators, have been considered to be primed for thermogenesis and thus not to show cold-acclimation effects, but here a significant increase in [3H]GDP-binding capacity was observed, and this increase was paralleled by an increase in thermogenin antigen amount, as measured in an enzyme-linked immunosorbent assay. The transient nature of the effect of cold exposure on [3H]GDP binding, characteristically observed with rat mitochondria, was not observed with hamster mitochondria, and the increase in [3H]GDP binding occurred without a change in the dissociation constant. The increase in thermogenin amount was paralleled by an increase both in GDP-sensitive Cl- permeability of the mitochondria and in GDP-sensitive respiration. It was established that it is the maximal activity of thermogenin that is rate limiting for thermogenesis in isolated mitochondria, provided that an optimal substrate is used (such as palmitoyl carnitine). Cold acclimation also increased the total amount of mitochondria in the tissue, leading totally to a sixfold increase in thermogenin content of the hamster. It is concluded that hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation

  16. Leucine Deprivation Decreases Fat Mass by Stimulation of Lipolysis in White Adipose Tissue and Upregulation of Uncoupling Protein 1 (UCP1) in Brown Adipose Tissue

    OpenAIRE

    Ying CHENG; Meng, Qingshu; Wang, Chunxia; Li, Houkai; Huang, Zhiying; Chen, Shanghai; Xiao, Fei; Guo, Feifan

    2009-01-01

    OBJECTIVE White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduction in abdominal fat mass. The cellular mechanisms responsible for this loss, however, are unclear. The goal of current study is to investigate possible mechanisms. RESEARCH DE...

  17. 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

  18. Stimulation of S14 mRNA and lipogenesis in brown fat by hypothyroidism, cold exposure, and cafeteria feeding: evidence supporting a general role for S14 in lipogenesis and lipogenesis in the maintenance of thermogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Freake, H.C.; Oppenheimer, J.H.

    1987-05-01

    In liver, thyroid hormone rapidly induces S14 mRNA, which encodes a small acidic protein. This sequence is abundantly expressed only in lipogenic tissues and is thought to have some function in fat metabolism. In the euthyroid rat, we measured 20-fold higher levels of S14 mRNA in interscapular brown adipose tissue than liver. Furthermore, whereas in liver or epididymal fat, hypothyroidism resulted in an 80% fall in S14 mRNA, in brown fat the level of this sequence increased a further 3-fold. In all three tissues, the expression of S14 mRNA correlated well with lipogenesis, as assessed by /sup 3/H/sub 2/O incorporation. Physiological activation of brown fat by chronic cold exposure or cafeteria feeding increased the concentration of S14 mRNA in this tissue and again this was accompanied by a greater rate of fatty acid synthesis. Overall, in liver and white and brown adipose tissue, S14 mRNA and lipogenesis were well correlated and strongly suggest a function of the S14 protein related to fat synthesis. These studies suggest that the S14 protein and lipogenesis may be important for thyroid hormone-induced and brown adipose tissue thermogenesis and that stimulation of these functions in hypothyroid brown fat is a consequence of decreased thyroid hormone-induced thermogenesis elsewhere.

  19. Stimulation of S14 mRNA and lipogenesis in brown fat by hypothyroidism, cold exposure, and cafeteria feeding: evidence supporting a general role for S14 in lipogenesis and lipogenesis in the maintenance of thermogenesis

    International Nuclear Information System (INIS)

    In liver, thyroid hormone rapidly induces S14 mRNA, which encodes a small acidic protein. This sequence is abundantly expressed only in lipogenic tissues and is thought to have some function in fat metabolism. In the euthyroid rat, we measured 20-fold higher levels of S14 mRNA in interscapular brown adipose tissue than liver. Furthermore, whereas in liver or epididymal fat, hypothyroidism resulted in an 80% fall in S14 mRNA, in brown fat the level of this sequence increased a further 3-fold. In all three tissues, the expression of S14 mRNA correlated well with lipogenesis, as assessed by 3H2O incorporation. Physiological activation of brown fat by chronic cold exposure or cafeteria feeding increased the concentration of S14 mRNA in this tissue and again this was accompanied by a greater rate of fatty acid synthesis. Overall, in liver and white and brown adipose tissue, S14 mRNA and lipogenesis were well correlated and strongly suggest a function of the S14 protein related to fat synthesis. These studies suggest that the S14 protein and lipogenesis may be important for thyroid hormone-induced and brown adipose tissue thermogenesis and that stimulation of these functions in hypothyroid brown fat is a consequence of decreased thyroid hormone-induced thermogenesis elsewhere

  20. 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.

  1. IGFBP-2 is a negative predictor of cold-induced brown fat and bone mineral density in young non-obese women

    OpenAIRE

    Bredella, Miriam A.; Fazeli, Pouneh K.; Lecka-Czernik, Beata; Rosen, Clifford J; Klibanski, Anne

    2013-01-01

    Recent studies have shown a positive correlation between brown adipose tissue (BAT) and bone mineral density (BMD). However, mechanisms underlying this relationship are unknown. Insulin-like growth factor 1 (IGF-1) is an important regulator of stem cell differentiation promoting bone formation. IGF binding protein 2 (IGFBP-2) binds IGF-1 in the circulation and has been reported to inhibit bone formation in humans. IGF-1 is also a crucial regulator of brown adipocyte differentiation. We hypoth...

  2. 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

  3. 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 laying hens. PMID:24235237

  4. 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...

  5. 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...

  6. 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

  7. 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...

  8. 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...

  9. 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...

  10. 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

  11. 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.

  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. 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

  14. 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...

  15. Inhomogeneity of photo-induced fat cell lipolysis

    Science.gov (United States)

    Doubrovsky, V. A.; Yanina, I. Yu.; Tuchin, V. V.

    2011-03-01

    The effect of optical properties changes of adipose tissue cells in vitro as a result of photoaction was found and investigated. The experimental study of photo-induced post action upon the cells of fat tissue by means of digital microscopy was fulfilled. The computer processing of digital photos obtained gave an opportunity to estimate quantitatively the level of photoaction upon tissue. Optical interpretation of photos obtained proves that the phenomenon observed corresponds to the lipolysis of adipose tissue cells, but without their complete destruction.

  16. White Fat Progenitor Cells Reside in the Adipose Vasculature

    OpenAIRE

    Tang, Wei; Zeve, Daniel; Suh, Jae Myoung; Bosnakovski, Darko; Kyba, Michael; Hammer, Robert E.; Tallquist, Michelle D.; Graff, Jonathan M.

    2008-01-01

    White adipose (fat) tissues regulate metabolism, reproduction, and life span. Adipocytes form throughout life, with the most marked expansion of the lineage occurring during the postnatal period. Adipocytes develop in coordination with the vasculature, but the identity and location of white adipocyte progenitor cells in vivo are unknown. We used genetically marked mice to isolate proliferating and renewing adipogenic progenitors. We found that most adipocytes descend from a pool of these prol...

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    Marlon E. Cerf

    2014-05-01

    Full Text Available 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, weanlings and adolescents maintained on a high fat diet during specific periods of fetal, lactational and/or postnatal life. Control neonates, weanlings and adolescents were maintained on a standard laboratory (control or low fat diet. Results Fetal high fat programmed (i.e., maintained on a high fat diet exclusively during fetal life neonates were insulin resistant. Weanlings maintained on a high fat diet throughout fetal and lactational life had increased pancreas weights. Fetal high fat programmed adolescents presented a normal phenotype mimicking the control adolescents. Adolescents maintained on a postnatal high fat diet had increased body weights, hyperglycemia, hyperinsulinemia, hyperleptinemia and insulin resistance displaying beta cell hypertrophy and increased islet cell proliferation. Adolescents maintained on a fetal and postnatal high fat diet had increased body weights, hyperleptinemia, hyperinsulinemia and insulin resistance. Conclusions High fat programming induces various diabetogenic phenotypes which present at different life stages. The postnatal period from birth to adolescence representsan extension for high fat programming of metabolic disease.

  19. 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.

  20. Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses

    OpenAIRE

    Vaughan, Cheryl H.; Bartness, Timothy J.

    2012-01-01

    Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensor...

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

    OpenAIRE

    Chakraborty, Dhritiman; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    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 per...

  2. 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...

  3. 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

  4. 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.

  5. 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

  6. Platycodon grandiflorum A. De Candolle Ethanolic Extract Inhibits Adipogenic Regulators in 3T3-L1 Cells and Induces Mitochondrial Biogenesis in Primary Brown Preadipocytes.

    Science.gov (United States)

    Kim, Hye-Lin; Park, Jinbong; Park, Hyewon; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; Jeong, Mi-Young; Um, Jae-Young

    2015-09-01

    This study was designed to evaluate the effects of Platycodon grandiflorum A. DC. ethanolic extract (PG) on obesity in brown/white preadipocytes. The effect of PG on the differentiation and mitochondrial biogenesis of brown adipocytes is still not examined. An in vivo study showed that PG induced weight loss in mice with high-fat-diet-induced obesity. PG successfully suppressed the differentiation of 3T3-L1 cells by down-regulating cellular induction of the peroxisome proliferators activated receptor γ (PPARγ), CCAAT enhancer binding protein α (C/EBPα), lipin-1, and adiponectin but increasing expression of silent mating type information regulation 2 homologue 1 (SIRT1) and the phosphorylation of AMP-activated protein kinase α (AMPKα). The effect of PG on the adipogenic factors was compared with that of its bioactive compound platycodin D. In addition, PG increased expressions of mitochondria-related genes, including uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor-coactivator 1 α (PGC1α), PR domain containing 16 (PRDM16), SIRT3, nuclear respiratory factor (NRF), and cytochrome C (CytC) in primary brown adipocytes. These results indicate that PG stimulates the differentiation of brown adipocytes through modulation of mitochondria-related genes and could offer clinical benefits as a supplement to treat obesity. PMID:26244589

  7. 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...

  8. Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

    OpenAIRE

    Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.

    2012-01-01

    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, urs...

  9. 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.

  10. Studies on fat cell function in human obesity and insulin resistance

    OpenAIRE

    Löfgren, Patrik

    2005-01-01

    Enlarged fat cells, due to excess tri-glyceride (TG) stores with increased basal lipolysis (TG breakdown) and blunted action of the major regulatory hormones of fat cell metabolism (catecholamines and insulin) are hallmarks of common obesity in humans. It is, however, not known whether these aberrations are caused by obesity per se or is a consequence of obesity. The aim of the present thesis was, firstly, to study the influence of obesity on hormonally induced fat cell meta...

  11. 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...

  12. Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell.

    Science.gov (United States)

    Barbato, Daniele Lettieri; Tatulli, Giuseppe; Aquilano, Katia; Ciriolo, Maria R

    2015-10-01

    Fasting promotes longevity by reprogramming metabolic and stress resistance pathways. However, although the impact on adipose tissue physiology through hormonal inputs is well established, the direct role of fasting on adipose cells is poorly understood. Herein we show that white and beige adipocytes, as well as mouse epididymal and subcutaneous adipose depots, respond to nutrient scarcity by acquiring a brown-like phenotype. Indeed, they improve oxidative metabolism through modulating the expression of mitochondrial- and nuclear-encoded oxidative phosphorylation genes as well as mitochondrial stress defensive proteins (UCP1, SOD2). Such adaptation is placed in a canonical mitohormetic response that proceeds via mitochondrial reactive oxygen species ((mt)ROS) production and redistribution of FoxO1 transcription factor into nucleus. Nuclear FoxO1 ((n)FoxO1) mediates retrograde communication by inducing the expression of mitochondrial oxidative and stress defensive genes. Collectively, our findings describe an unusual white/beige fat cell response to nutrient availability highlighting another health-promoting mechanism of fasting. PMID:26540513

  13. 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

  14. 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.

  15. 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...

  16. The Relationship of a Combination of Human Adipose Tissue-Derived Stem Cells and Frozen Fat with the Survival Rate of Transplanted Fat

    OpenAIRE

    Ha, Ki-Young; Park, Hojin; Park, Seung-Ha; Lee, Byung-Il; Ji, Yi-Hwa; Kim, Tae-Yeon; Yoon, Eul-Sik

    2015-01-01

    Background The survival rate of grafted fat is difficult to predict, and repeated procedures are frequently required. In this study, the effects of the freezing period of harvested adipose tissue and the addition of human adipose tissue-derived stem cells (ASCs) on the process of fat absorption were studied. Methods Adipose tissue was obtained from patients who underwent a lipoaspirated fat graft. The fat tissue was cryopreserved at -20℃ in a domestic refrigerator. A total of 40 nude mice wer...

  17. Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism

    Directory of Open Access Journals (Sweden)

    Hee-Jin Jun

    2012-01-01

    Full Text Available Brown fat expresses two PGC-1α isoforms (PGC-1α and NT-PGC-1α and both play a central role in the regulation of cellular energy metabolism and adaptive thermogenesis by interacting with a wide range of transcription factors including PPARγ, PPARα, ERRα, and NRF1. PGC-1α consists of 797 amino acids, whereas alternative splicing of the PGC-1α gene produces a shorter protein called NT-PGC-1α (aa 1–270. We report in this paper that transcriptional activity of PGC-1α and NT-PGC-1α is differently affected by the transcriptional regulator, Twist-1. Twist-1 suppresses PGC-1α but not NT-PGC-1α. The inhibition of PGC-1α activity by Twist-1 is mediated by direct interaction through the C-terminal region of PGC-1α (aa 353–797. Thus, the absence of the corresponding C-terminal domain in NT-PGC-1α allows NT-PGC-1α to be free from Twist-1-mediated inhibition. Overexpression of Twist-1 in brown adipocytes suppresses transcription of a subset of PGC-1α-target genes involved in mitochondrial fatty acid oxidation and uncoupling (CPT1β, UCP1, and ERRα. In contrast, NT-PGC-1α-mediated induction of these genes is unaffected by Twist-1. These findings show that differences in inhibitory protein-protein interactions of PGC-1α and NT-PGC-1α with Twist-1 lead to differential regulation of their function by Twist-1.

  18. 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 ...

  19. 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...

  20. 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...... downregulated in mice exposed to cold, resulting in de novo generation of satellite cell-derived brown adipocytes. Therefore, microRNA-133 represents an important therapeutic target for the treatment of obesity....

  1. 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

  2. Insulin-stimulated phosphoinositide metabolism in isolated fat cells

    International Nuclear Information System (INIS)

    Treatment of isolated fat cells with insulin produced increases of up to 4.8-fold in the incorporation of [3H]inositol into phosphatidylinositol. This effect of insulin was both time- and dose-dependent with half-maximal stimulation at 30 microunits/ml of insulin. Insulin increased the labeling of phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate but not phosphatidylinositol 4-monophosphate in cells which had been preincubated with [3H]inositol for 90 min. Incubation of the cells in a Ca2+-free buffer increased the basal level of phosphatidylinositol labeling and enhanced the effect of insulin. Glucagon and isoprenaline, both of which stimulate lipolysis, had no effect on phosphatidylinositol labeling but did potentiate insulin-stimulated incorporation of [3H]inositol into phosphatidylinositol. Phosphoinositide breakdown was measured by the accumulation of inositol phosphates. Insulin did not increase the level of the inositol phosphates at all concentrations of the hormone tested. By comparison, phenylephrine and vasopressin were able to stimulate phosphoinositide breakdown. Pretreatment of the cells with insulin enhanced the effect of phenylephrine on inositol phosphates accumulation, suggesting that insulin may potentiate phenylephrine-mediated phosphoinositide turnover. From these data the author conclude that insulin stimulates the de novo synthesis of phosphatidylinositol and phosphatidylinositol 4,5-biphosphate, but has no effect on phosphoinositide breakdown

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

    Energy Technology Data Exchange (ETDEWEB)

    Wu, S.Y.; Stern, J.S.; Fisher, D.A.; Glick, Z.

    1987-01-01

    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 (T/sub 4/) to triiodothyronine (T/sub 3/) in BAT. A total of 34 lean and obese rats, approx.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 +/- 1/sup 0/C) for 7 days. Activity of T/sub 4/ 5'-deiodinase was determined as the rate of T/sub 3/ production from added T/sub 4/ under controlled in vitro conditions. Serum T/sub 4/ and T/sub 3/ were determined by radioimmunoassay. The rate of T/sub 4/-to-T/sub 3/ 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 T/sub 3/ production whereas only a small increase was observed in the cold-exposed obese rats. Serum T/sub 3/ levels tended to be reduced in the Zucker obese rats. The data indicate a reduced capacity for T/sub 3/ 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.

  4. 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...

  5. 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.)

  6. 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.

  7. 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. PMID:26569380

  8. 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

  9. 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.

  10. Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture

    International Nuclear Information System (INIS)

    In order to characterize the biogenesis of unique thermogenic mitochondria of brown adipose tissue, differentiation of precursor cells isolated from mouse brown adipose tissue was studied in cell culture. Synthesis of mitochondrial uncoupling protein (UCP), F1-ATPase, and cytochrome oxidase was examined by L-[35S]methionine labeling and immunoblotting. For the first time, synthesis of physiological amounts of the UCP, a key and tissue-specific component of thermogenic mitochondria, was observed in cultures at about confluence (day 6), indicating that a complete differentiation of brown adipocytes was achieved in vitro. In postconfluent cells (day 8) the content of UCP decreased rapidly, in contrast to some other mitochondrial proteins (beta subunit of F1-ATPase, cytochrome oxidase). In these cells, it was possible, by using norepinephrine, to induce specifically the synthesis of the UCP but not of F1-ATPase or cytochrome oxidase. The maximal response was observed at 0.1 microM norepinephrine and the synthesis of UCP remained activated for at least 24 h. Detailed analysis revealed a major role of the beta-adrenergic receptors and elevated intracellular concentration of cAMP in stimulation of UCP synthesis. A quantitative recovery of the newly synthesized UCP in the mitochondrial fraction indicated completed biogenesis of functionally competent thermogenic mitochondria

  11. IGFBP-2 is a negative predictor of cold-induced brown fat and bone mineral density in young non-obese women.

    Science.gov (United States)

    Bredella, Miriam A; Fazeli, Pouneh K; Lecka-Czernik, Beata; Rosen, Clifford J; Klibanski, Anne

    2013-04-01

    Recent studies have shown a positive correlation between brown adipose tissue (BAT) and bone mineral density (BMD). However, mechanisms underlying this relationship are unknown. Insulin-like growth factor 1 (IGF-1) is an important regulator of stem cell differentiation promoting bone formation. IGF binding protein 2 (IGFBP-2) binds IGF-1 in the circulation and has been reported to inhibit bone formation in humans. IGF-1 is also a crucial regulator of brown adipocyte differentiation. We hypothesized that IGFBP-2 is a negative and IGF-1 a positive regulator of BAT-mediated osteoblastogenesis. We therefore investigated a cohort of 15 women (mean age 27.7±5.7years): 5 with anorexia nervosa (AN) in whom IGF-1 levels were low due to starvation, 5 recovered AN (AN-R), and 5 women of normal weight. All subjects underwent assessment of cold-activated BAT by PET/CT, BMD of the spine, hip, femoral neck, and total body by DXA, thigh muscle area by MRI, IGF-1 and IGFBP-2. There was a positive correlation between BAT and BMD and an inverse association between IGFBP-2 and both BAT and BMD. There was no association between IGF-1 and BAT. We show for the first time that IGFBP-2 is a negative predictor of cold-induced BAT and BMD in young non-obese women, suggesting that IGFBP-2 may serve as a regulator of BAT-mediated osteoblastogenesis. PMID:23291564

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

    Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo...... 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...

  17. Both liver-X receptor (LXR) isoforms control energy expenditure by regulating Brown Adipose Tissue activity

    OpenAIRE

    Korach-André, Marion; Archer, Amena; Barros, Rodrigo P.; Parini, Paolo; Gustafsson, Jan-Åke

    2010-01-01

    Brown adipocytes are multilocular lipid storage cells that play a crucial role in nonshivering thermogenesis. Uncoupling protein 1 (UCP1) is a unique feature of brown fat cells that allows heat generation on sympathetic nervous system stimulation. As conventional transcriptional factors that are activated in various signaling pathways, liver-X receptors (LXRs) play important roles in many physiological processes. The role of LXRs in the regulation of energy homeostasis remains unclear, howeve...

  18. 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.

  19. Cell-Autonomous Brown-Like Adipogenesis of Preadipocytes From Retinoblastoma Haploinsufficient Mice.

    Science.gov (United States)

    Petrov, Petar D; Palou, Andreu; Bonet, M Luisa; Ribot, Joan

    2016-09-01

    Mechanisms behind the emergence of brown adipocyte-like (brite or beige) adipocytes within white adipose tissue (WAT) are of interest. Retinoblastoma protein gene (Rb) haploinsufficiency associates in mice with improved metabolic regulation linked to a greater capacity for fatty acid oxidation and thermogenesis in WAT. We aimed to explain a feasible mechanism of WAT-to-BAT remodeling in this model. Differentiated primary adipocytes and Sca1-positive preadipocytes derived from adipose depots of Rb(+/-) mice and wild-type siblings were compared. Primary white Rb(+/-) adipocytes displayed under basal conditions increased glucose uptake and an enhanced expression of brown adipocyte-related genes (Pparg, Ppargc1a, Ppargc1b, Prdm16, Cpt1b) but not of purported beige/brite transcriptional markers (Cd137, Tmem26, Tbx1, Slc27a1, Hoxc9, Shox2). Lack of induction of beige markers phenocopied results in WAT of adult Rb(+/-) mice. Flow cytometry analysis evidenced an increased number of preadipocytes in WAT depots of Rb(+/-) mice. Sca1(+) preadipocytes from WAT of Rb(+/-) mice displayed increased gene expression of several transcription factors common to the brown and beige adipogenic programs (Prdm16, Pparg, Ppargc1a) and of receptors of bone morphogenetic proteins (BMPs); however, among the recently proposed beige markers, only Tbx1 was upregulated. Adult Rb(+/-) mice had increased circulating levels of BMP7. These results indicate that preadipose cells resident in WAT depots of Rb(+/-) mice retain an increased capacity for brown-like adipogenesis that appears to be different from beige adipogenesis, and suggest that the contribution of these precursors to the Rb(+/-) adipose phenotype is driven, at least in part, by interaction with BMP7 pathways. J. Cell. Physiol. 231: 1941-1952, 2016. © 2016 Wiley Periodicals, Inc. PMID:26727985

  20. 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...

  1. 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...

  2. 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.

  3. 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.

  4. ASK1 signalling regulates brown and beige adipocyte function.

    Science.gov (United States)

    Hattori, Kazuki; Naguro, Isao; Okabe, Kohki; Funatsu, Takashi; Furutani, Shotaro; Takeda, Kohsuke; Ichijo, Hidenori

    2016-01-01

    Recent studies suggest that adult humans have active brown or beige adipocytes, the activation of which might be a therapeutic strategy for the treatment of diverse metabolic diseases. Here we show that the protein kinase ASK1 regulates brown and beige adipocytes function. In brown or white adipocytes, the PKA-ASK1-p38 axis is activated in response to cAMP signalling and contributes to the cell-autonomous induction of genes, including Ucp1. Global and fat-specific ASK1 deficiency leads to impaired metabolic responses, including thermogenesis and oxygen consumption, at the cell and whole-body levels, respectively. Our data thus indicate that the ASK1 signalling axis is a regulator of brown and beige adipocyte gene expression and function. PMID:27045525

  5. Cell autonomous lipin 1 function is essential for development and maintenance of white and brown adipose tissue.

    Science.gov (United States)

    Nadra, Karim; Médard, Jean-Jacques; Mul, Joram D; Han, Gil-Soo; Grès, Sandra; Pende, Mario; Metzger, Daniel; Chambon, Pierre; Cuppen, Edwin; Saulnier-Blache, Jean-Sébastien; Carman, George M; Desvergne, Béatrice; Chrast, Roman

    2012-12-01

    Through analysis of mice with spatially and temporally restricted inactivation of Lpin1, we characterized its cell autonomous function in both white (WAT) and brown (BAT) adipocyte development and maintenance. We observed that the lipin 1 inactivation in adipocytes of aP2(Cre/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice resulted in lipodystrophy and the presence of adipocytes with multilocular lipid droplets. We further showed that time-specific loss of lipin 1 in mature adipocytes in aP2(Cre-ERT2/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice led to their replacement by newly formed Lpin1-positive adipocytes, thus establishing a role for lipin 1 in mature adipocyte maintenance. Importantly, we observed that the presence of newly formed Lpin1-positive adipocytes in aP2(Cre-ERT2/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice protected these animals against WAT inflammation and hepatic steatosis induced by a high-fat diet. Loss of lipin 1 also affected BAT development and function, as revealed by histological changes, defects in the expression of peroxisome proliferator-activated receptor alpha (PPARα), PGC-1α, and UCP1, and functionally by altered cold sensitivity. Finally, our data indicate that phosphatidic acid, which accumulates in WAT of animals lacking lipin 1 function, specifically inhibits differentiation of preadipocytes. Together, these observations firmly demonstrate a cell autonomous role of lipin 1 in WAT and BAT biology and indicate its potential as a therapeutical target for the treatment of obesity. PMID:23028044

  6. 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.

  7. 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...

  8. 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.

  9. 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...

  10. Glucagon-insulin interaction on fat cell metabolism using c14 glucose

    International Nuclear Information System (INIS)

    Glucagon is known to stimulate the lipolysis in isolated fat cells from young rats, but not in fat cells from old heavy rate (Manganiello 1972). Insulin is known to counteract the lipolytic effect and to stimulate the synthesis of fatty acids from glucose. However, little is known about the interaction between the two hormones on the glucose metabolism. Experiments based on the use of various inhibitors of lipolysis have however, clearly shown that glucagon can also stimulate the entry and overall oxidation of glucose by mechanism which is distinct from its lipolysis stimulating mechanism (M. Blecher et al. 1969). Fat cells from old heavy rats are known to be less responsive to both the lipogenic action of insulin and the lipolytic action of glucagon than fat cells from young lean rats (E.G. Hansen, Nielsen and Gliemann, 1974). The aim of the present study was to see how glucagon affects glucose metabolism in fat cells, and whether this effect was dependent on the lipolytic action of glucagon

  11. 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...

  12. 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

    adipocyte precursor cells (APCs) isolated from visceral and subcutaneous white adipose depots of mice have distinct patterns of gene expression, differentiation potential, and response to environmental and genetic influences. APCs derived from subcutaneous fat differentiate well in the presence of classical......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 that...... induction cocktail, whereas those from visceral fat differentiate poorly but can be induced to differentiate by addition of bone morphogenetic protein (BMP)-2 or BMP-4. This difference correlates with major differences in gene expression signature between subcutaneous and visceral APCs. The number of APCs...

  13. 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

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

    International Nuclear Information System (INIS)

    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

  15. 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...

  16. 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

  17. Abalation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues

    Science.gov (United States)

    Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show ...

  18. Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell

    OpenAIRE

    Barbato, Daniele Lettieri; Tatulli, Giuseppe; Aquilano, Katia; Ciriolo, Maria R.

    2015-01-01

    Fasting promotes longevity by reprogramming metabolic and stress resistance pathways. However, although the impact on adipose tissue physiology through hormonal inputs is well established, the direct role of fasting on adipose cells is poorly understood. Herein we show that white and beige adipocytes, as well as mouse epididymal and subcutaneous adipose depots, respond to nutrient scarcity by acquiring a brown-like phenotype. Indeed, they improve oxidative metabolism through modulating the ex...

  19. 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...

  20. 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.

  1. Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat. Neural site of action.

    OpenAIRE

    Kotz, C.M.; Grace, M.K.; Briggs, J.; Levine, A S; Billington, C.J.

    1995-01-01

    Neuropeptide Y administered intracerebroventricularly and into the paraventricular nucleus of the hypothalamus stimulates feeding and decreases brown adipose tissue thermogenesis. Although specific neuropeptide Y antagonists are not yet available, previous studies had shown that the opioid antagonist naloxone blocked neuropeptide Y-induced feeding when both drugs were injected intracerebroventricularly. We wanted to find out if naloxone injected into specific brain sites would block neuropept...

  2. 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...

  3. 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.

  4. 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...

  5. Angiomyolipoma with minimal fat: Differentiation from papillary renal cell carcinoma by helical CT

    International Nuclear Information System (INIS)

    Aim: To evaluate whether helical computed tomography (CT) images can be used to differentiate angiomyolipomas (AMLs) with minimal fat from papillary renal cell carcinomas (PRCCs) based on their morphological characteristics and enhancement features. Materials and methods: This retrospective study was approved by the institutional review board. Informed consent was waived. Forty-four patients (21 with AMLs with minimal fat and 23 with PRCCs) who underwent enhanced helical CT before total or partial nephrectomy were included. Two radiologists, who were blinded to the histopathology results, read the CT images and recorded the attenuation value, morphological characteristics, and enhancement features of the tumours, which were subsequently evaluated. An independent samples t-test, χ2 test, and rank sum test were performed between the tumours. The predictive value of a CT finding was determined by multivariate logistic regression analysis. Results: AML with minimal fat had an apparent female prevalence (p < 0.01). Intra-tumoural vessels were noted in 11 cases of AML with minimal fat and three PRCC cases (p < 0.01). The unenhanced attenuation characteristic was significantly different between the two diseases (p < 0.001). The absolute attenuation values (AAVs) and the corrected attenuation values (CAVs) of the AML with minimal fat group of unenhanced and two phases of enhanced images were greater compared with that of the PRCC group (p < 0.05). After contrast medium injection, the tumour enhancement value (TEV) of the AML with minimal fat group in the corticomedullary phase was greater than that of the PRCC group (p < 0.01). Most cases of both tumour types demonstrated early enhancement characteristics; the enhancement value of the AML with minimal fat group was greater compared with that of the PRCC group (p < 0.01). The unenhanced attenuation characteristic, intra-tumoural vessels, and CAVs of unenhanced and early excretory phase scans were valuable parameters to

  6. 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.

  7. 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 ...

  8. 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

  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. Advantages of Sheep Infrapatellar Fat Pad Adipose Tissue Derived Stem Cells in Tissue Engineering

    Science.gov (United States)

    Vahedi, Parviz; Soleimanirad, Jafar; Roshangar, Leila; Shafaei, Hajar; Jarolmasjed, Seyedhosein; Nozad Charoudeh, Hojjatollah

    2016-01-01

    Purpose: The goal of this study has been to evaluate adipose tissue derived stem cells (ADSCs) from infrapatellar fat pad and characterize their cell surface markers using anti-human antibodies, as adipose tissue derived stem cells (ADSCs) have great potential for cellular therapies to restore injured tissues. Methods: Adipose tissue was obtained from infrapatellar fat pad of sheep. Surface markers evaluated by flow cytometry. In order to evaluate cell adhesion, the Polycaprolactone (PCL) was sterilized under Ultraviolet (UV) light and about 1×105 cells were seeded on PCL. Then, ASCs- PCL construct were evaluated by Scanning Electron Microscopy (Mira3 Te Scan, Czech Republic). Results: We showed that adipose tissue derived stem cells (ADSCs) maintain their fibroblastic-like morphology during different subcultures and cell adhesion. They were positive for CD44 and CD90 markers and negative for CD31 and Cd45 markers by human antibodies. Conclusion: Our results suggest that ASCs surface markers can be characterized by anti-human antibodies in sheep. As stem cells, they can be used in tissue engineering. PMID:27123425

  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. Effect of epinephrine and insulin on glucose metabolism in isolated fat cells

    International Nuclear Information System (INIS)

    Since epinephrine and insulin are known to counteract each other in several metabolic respects, it was found of interest to evaluate the interaction of these hormones on glucose metabolism in isolated fat cells. Results indicate that in spite of reduced lipolysis, insulin potentiates the conversion of glucose to glyceride-glycerol. This means that a certain degree of esterification of fatty acids must take place. So the low rate of lipolysis is sufficient to provide fatty acids for this esterification. (author)

  14. Effect of epinephrine and insulin on glucose metabolism in isolated fat cells

    Energy Technology Data Exchange (ETDEWEB)

    Zewail, M.A. (National Research Centre, Cairo (Egypt)); Fahmy, N.M. (National Organisation for Drug Control and Research, Cairo (Egypt)); Nielsen, J.H. (Gentofte Hospital, Copenhagen (Denmark))

    1984-08-01

    Since epinephrine and insulin are known to counteract each other in several metabolic respects, it was found of interest to evaluate the interaction of these hormones on glucose metabolism in isolated fat cells. Results indicate that in spite of reduced lipolysis, insulin potentiates the conversion of glucose to glyceride-glycerol. This means that a certain degree of esterification of fatty acids must take place. So the low rate of lipolysis is sufficient to provide fatty acids for this esterification.

  15. The inhibition of fat cell proliferation by fatty acids in dietary obese mice

    Czech Academy of Sciences Publication Activity Database

    Hensler, Michal; Bardová, Kristina; Macek Jílková, Zuzana; Wahli, W.; Meztger, D.; Chambon, P.; Kopecký, Jan; Flachs, Pavel

    2011-01-01

    Roč. 10, - (2011), s. 128. ISSN 1476-511X R&D Projects: GA ČR(CZ) GAP301/11/0226; GA ČR(CZ) GD305/08/H037 Institutional research plan: CEZ:AV0Z50110509 Keywords : DHA and EPA * fish oil * fat cell turnover Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.170, year: 2011

  16. 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. PMID:27122175

  17. 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

  18. 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

  19. Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

    International Nuclear Information System (INIS)

    This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [3H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

  20. Cytoplasmic fat detection utilizing chemical shift gradient. Echo MR imaging in cases of clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    We investigated whether cytoplasmic fat in clear cell renal cell carcinoma (CCC) can be identified by chemical shift gradient-echo magnetic resonance imaging (CSI). CSI was performed for 22 cases of CCC and 30 cases of other renal tumors (including 16 cases of non-CCC), all of which were surgically proven. Signal reduction in out-of-phase images of these tumors was retrospectively evaluated and compared. The signal loss ratio (SLR) was defined and calculated. Fat staining of specimens from 16 tumors was performed and correlated with SLR. SLR was found to be significantly higher in CCC than in non-CCC (p<0.002). There was a significant correlation between the degree of fat staining positively of the specimens and SLR (p<0.01). When signal reduction in out-of-phase images suggested a diagnosis of CCC, a correct diagnosis of this entity was made in the resected renal tumors with a sensitivity, specificity, and accuracy of 82%, 93%, and 88%, respectively. CSI can demonstrate cytoplasmic fat in CCC, which helps to differentiate this entity from other renal tumors. (author)

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

    Czech Academy of Sciences Publication Activity Database

    Geldermann, H.; Čepica, Stanislav; Stratil, Antonín; Bartenschlager, H.; Preuss, S.

    2010-01-01

    Roč. 42, č. 31 (2010), s. 1-16. ISSN 0999-193X R&D Projects: GA ČR GA523/07/0353; GA ČR(CZ) GA523/06/1302 Institutional research plan: CEZ:AV0Z50450515 Keywords : fat metabolism * porcine * genome mapping Subject RIV: GI - Animal Husbandry ; Breeding Impact factor: 1.484, year: 2010

  2. 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.

  3. Phagocytosis mechanism of apoptotic granulosa cells regulated by milk-fat globule-EGF factor 8.

    Science.gov (United States)

    Naka, Mayumi; Kusakabe, Ken; Takeshita, Ai; Nakagawa, Hiroshi; Ito, Yuko; Shibata, Masa-Aki; Otsuki, Yoshinori

    2009-09-01

    In the process of ovary sexual maturation, most immature ovarian follicles degrade into atretic follicles accompanied by apoptosis in granulosa cells. Macrophages can recognize apoptotic cells through specific binding with phosphatidylserine (PS), exposed on the surface of apoptotic cells, which is mediated by milk-fat globule-EGF factor 8 (MFG-E8). In the present research, we examined the involvement of the MFG-E8-dependent phagocytosis system in the atretic follicles of developing mouse ovaries. The number of atretic follicles and DNA-fragmented granulosa cells significantly increased in B6C3F1 mice during 2 to 6 weeks. Chromatin-condensed granulosa cells were engulfed by macrophages, which existed in the stroma or atretic follicles, or by neighboring normal granulosa cells. MFG-E8 mRNA increased in ovaries during 2 to 6 weeks, and immunoreactivity of MFG-E8 was detected at the surface of apoptotic cells existing around the antrum. Immunoelectron microscopic study revealed MFG-E8-positive signals on the membrane of apoptotic cells near macrophages, but apoptotic cells engulfed by neighboring granulosa cells showed few signals. Anti-Fas antibody elevated the annexin-V-positive reaction in isolated granulosa cells from 3-week-old mouse ovaries. MFG-E8 seems to act on the phagocytosis of apoptotic granulosa cells via macrophages and contribute to the regression process of atretic follicles. PMID:19784740

  4. Comparative integromics on FAT1, FAT2, FAT3 and FAT4.

    Science.gov (United States)

    Katoh, Yuriko; Katoh, Masaru

    2006-09-01

    WNT5A, WNT5B, WNT11, FZD3, FZD6, VANGL1, VANGL2, DVL1, DVL2, DVL3, PRICKLE1, PRICKLE2, ANKRD6, NKD1, NKD2, DAAM1, DAAM2, CELSR1, CELSR2, CELSR3, ROR1 and ROR2 are planar cell polarity (PCP) signaling molecules implicated in the regulation of cellular polarity, convergent extension, and invasion. FAT1, FAT2, FAT3 and FAT4 are Cadherin superfamily members homologous to Drosophila Fat, functioning as a positive regulator of PCP in the Drosophila wing. Complete coding sequence (CDS) for human FAT1 (NM_005245.3) and FAT2 (NM_001447.1) are available, while artificial CDS for human FAT3 (XM_926199 and XM_936538) and partial CDS for FAT4 (NM_024582.2). Here, complete CDS of human FAT3 and FAT4 were determined by using bioinformatics and human intelligence (Humint). FAT3 gene, consisting of 26 exons, encoded a 4557-aa protein with extracellular 33 Cadherin repeats, one Laminin G (LamG) domain and two EGF domains. FAT4 gene encoded a 4924-aa protein with extracellular 34 Cadherin repeats, two LamG domains and three EGF domains. Cytoplasmic VCSVxPxLP and SDYxS motifs were identified as novel motifs conserved among FAT1, FAT2 and FAT3 orthologs. Domain architecture comparison and phylogenetic analysis revealed that FAT1, FAT2 and FAR3 were divergent from FAT4. FAT1-MTNR1A locus at 4q35.2 and FAT3-MTNR1B locus at 11q14.3-q21 were paralogous regions within the human genome. FAT1 mRNA was expressed in embryonic stem (ES) cells, neural tissues, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, lung cancer and brain tumors. FAT2 mRNA was expressed in infant brain, cerebellum, gastric cancer, pancreatic cancer, ovarian cancer, esophageal cancer, skin squamous cell carcinoma, head and neck cancer. FAT3 mRNA was expressed in ES cells, primitive neuroectoderm, fetal brain, infant brain, adult neural tissues and prostate. FAT4 mRNA was expressed in fetal brain, infant brain, brain tumor and colorectal cancer. FAT family members were revealed to be targets of systems

  5. Improved adipogenic in vitro differentiation: comparison of different adipogenic cell culture media on human fat and bone stroma cells for fat tissue engineering.

    Science.gov (United States)

    Ghoniem, Amir-Alexander; Açil, Yahya; Wiltfang, Jörg; Gierloff, Matthias

    2015-06-01

    To date there is no sufficient in vitro fat tissue engineering and a protocol has not been well established for this purpose. Therefore, we evaluated the in vitro influence of two different adipogenic growth media for their stimulation potential on different cell lineages to clearly define the most potent adipogenic growth media for future in vitro tissue engineering approaches. The samples for differentiation were composed of human adipogenic-derived stroma cells (hADSCs) and human bone marrow mesenchymal stroma cells (hMSCs). A normal adipogenic medium (NAM) and a specific adipogenic medium (SAM) were tested for their adipogenic stimulation potential. After 10 days and 21 days the relative gene expression was measured for the adipogenic marker genes PPARγ2, C/EBPα, FABP4, LPL, and GLUT4 detected through real time reverse transcriptase polymease chain reaction (RT-PCR). Other study variables were the comparison between NAM and SAM and between the used cells hADSCs and hMSCs. Additionally an Oil-Red staining was performed after 21 days. Our results revealed that only SAM was significantly (Pwell was SAM superior to differentiate the used cell lineages. This was evaluated by the detected marker genes PPARγ2, C/EBPα, FABP4, LPL, and GLUT4 through real time RT-PCR and by Oil-Red staining. In addition, the hMSCs proofed to be equal donor cells for adipogenic differentiation especially when stimulated by SAM. The results suggest that the SAM should be established as a new standard medium for a more promising in vitro adipogenic differentiation. PMID:26140219

  6. Uptake and clearance of plutonium-238 from liver cells transplanted into fat pads of F344 rats

    International Nuclear Information System (INIS)

    Animals injected with liver cells and control animals received a single intraperitoneal injection of 37 kBq (1 μCi) 238Pu citrate and were serially sacrificed. It was observed that the cells of the intact liver took up about twice as much 238Pu as liver cells transplanted into the fat pads of the same animal. The retention half-life was 8.3 days for the total activity in the liver, 20 days using tracks/cell measurements in the liver and 16 days for the tracks/cell measurements in the liver cells translocated to fat pads. When the data on tracks/cell were standardized relative to the amount of Pu present at 5 days after injection, there was no significant difference between the retention of Pu in liver cells from intact animals and liver cells transplanted into the fat pads. About 20% of the 5-day Pu liver burden in both liver cells and liver cells transplanted into fat pads was retained at 70 days. The smaller retention and clearance for liver cells in different environments indicate that uptake and clearance of Pu from the body is dependent, to a major extent, upon hepatocyte function. (author)

  7. 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.

  8. 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...

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Cell Autonomous Lipin 1 Function Is Essential for Development and Maintenance of White and Brown Adipose Tissue

    OpenAIRE

    Nadra, Karim; Médard, Jean-Jacques; Mul, Joram D.; Han, Gil-Soo; Grès, Sandra; Pende, Mario; Metzger, Daniel; Chambon, Pierre; Cuppen, Edwin; Saulnier-Blache, Jean-Sébastien; Carman, George M.; Desvergne, Béatrice; Chrast, Roman

    2012-01-01

    Through analysis of mice with spatially and temporally restricted inactivation of Lpin1, we characterized its cell autonomous function in both white (WAT) and brown (BAT) adipocyte development and maintenance. We observed that the lipin 1 inactivation in adipocytes of aP2Cre/+/LpfEx2-3/fEx2-3 mice resulted in lipodystrophy and the presence of adipocytes with multilocular lipid droplets. We further showed that time-specific loss of lipin 1 in mature adipocytes in aP2Cre-ERT2/+/LpfEx2-3/fEx2-3 ...

  14. 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

  15. 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

  16. Milk fat globule is an alternative to mammary epithelial cells for gene expression analysis in buffalo.

    Science.gov (United States)

    Chen, Qiuming; Wu, Yanjun; Zhang, Mingyuan; Xu, Wenwen; Guo, Xiaoping; Yan, Xueyu; Deng, Haiying; Jiang, Qinyang; Yang, Xiurong; Lan, Ganqiu; Guo, Yafen; Qin, Guangsheng; Jiang, Hesheng

    2016-05-01

    Owing to the difficulty in obtaining mammary gland tissue from lactating animals, it is difficult to test the expression levels of genes in mammary gland. The aim of the current study was to identify if milk fat globule (MFG) in buffalo milk was an alternative to mammary gland (MG) and milk somatic cell (MSC) for gene expression analysis. Six buffalos in late lactation were selected to collect MFG and MSC, and then MG was obtained by surgery. MFG was stained with acridine orange to successfully visualise RNA and several cytoplasmic crescents in MFG. The total RNA in MFG was successfully isolated and the integrity was assessed by agarose gel electrophoresis. We analysed the cellular components in MFG, MG and MSC through testing the expression of cell-specific genes by qRT-PCR. The results showed that adipocyte-specific gene (AdipoQ) and leucocyte-specific genes (CD43, CSF1 and IL1α) in MFG were not detected, whereas epithelial cell marker genes (Keratin 8 and Keratin 18) in MFG were higher than in MSC and lower than in MG, fibroblast marker gene (vimentin) in MFG was significantly lower than in MG and MSC, milk protein genes (LALBA, BLG and CSN2) and milk fat synthesis-related genes (ACC, BTN1A1, FABP3 and FAS) in MFG were higher than in MG and MSC. In conclusion, the total RNA in MFG mainly derives from mammary epithelial cells and can be used to study the functional gene expression of mammary epithelial cells. PMID:27032540

  17. Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells

    OpenAIRE

    Park, Anna; Kim, Won Kon; Bae, Kwang-Hee

    2014-01-01

    Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue (WAT) or brown adipose tissue (BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced...

  18. 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...

  19. Mono(2-ethylhexyl)phthalate accumulation disturbs energy metabolism of fat cells.

    Science.gov (United States)

    Chiang, Huai-Chih; Kuo, Ya-Ting; Shen, Chih-Che; Lin, Yi-Hua; Wang, Shu-Li; Tsou, Tsui-Chun

    2016-03-01

    Phthalates are lipophilic and tend to accumulate in adipose tissue, an important regulator of energy balance and glucose homeostasis. The study aimed to determine whether cellular phthalate accumulation influenced fat cell energy metabolism. Following a 3-day treatment with adipogenesis-inducing medium and a 2-day treatment with adipogenesis-maintaining medium, 3T3-L1 cells differentiated into adipocytes in the presence of a phthalate at a clinically relevant concentration (30-300 μM) for another 6 days. Two phthalates, di(2-ethylhexyl)phthalate and di-n-butylphthalate, and their metabolites, mono(2-ethylhexyl)phthalate (MEHP) and mono-n-butylphthalate, were used here. The phthalate treatments caused no marked effect on cytotoxicity and adipogenesis. Only the MEHP-treated adipocytes were found having smaller lipid droplets; MEHP accumulated in cells in a dose- and time-dependent manner. The MEHP-treated adipocytes exhibited significant increases in lipolysis and glucose uptake; quantitative real-time polymerase chain reaction (qPCR) analysis revealed correlated changes in expression of marker genes involved in adipogenesis, lipid metabolism, and glucose uptake. Analysis of oxygen consumption rate (a mitochondrial respiration indicator) and extracellular acidification rate (a glycolysis indicator) indicated a higher energy metabolism in the adipocytes. qPCR analysis of critical genes involved in mitochondrial biogenesis and/or energy metabolism showed that expression of peroxisome proliferator-activated receptor γ coactivator-1α, sirtuin 3, and protein kinase A were significantly enhanced in the MEHP-treated adipocytes. In vitro evidence of MEHP impacts on lipolysis, glucose uptake/glycolysis, and mitochondrial respiration/biogenesis demonstrates that MEHP accumulation disturbs energy metabolism of fat cells. PMID:25543134

  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. 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. PMID:25150689

  2. 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.

  3. 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...

  4. 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

  5. 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

  6. Changes in catecholamine-induced lipolysis in isolated human fat cells during the first year of life.

    OpenAIRE

    Marcus, C; B. Karpe; Bolme, P; Sonnenfeld, T; Arner, P

    1987-01-01

    Catecholamine-induced lipolysis in isolated human adipocytes during the first year of life was investigated. During this period fat cell size increased markedly. Basal and catecholamine-induced glycerol release were positively correlated with age when lipolysis was expressed per cell. However, when lipolysis was expressed per unit of cell surface area (micrometer squared), this correlation was observed only for noradrenaline. Basal lipolysis and the effect of the pure beta-agonist, isoprenali...

  7. 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 ......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...

  8. Diffusion-weighted magnetic resonance imaging in the differentiation of angiomyolipoma with minimal fat from clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    The aim of the present study was to evaluate diffusion-weighted (DW) magnetic resonance imaging (MRI) in differentiating between minimal fat angiomyolipoma (MFAML) and clear cell renal cell carcinoma (CCRCC). Forty-one solid renal tumors without visible macroscopic fat on unenhanced computed tomography images were evaluated by MRI, including DW-MRI, and were diagnosed pathologically as CCRCC (n=36) or MFAML (n=5). To evaluate the heterogeneity of diffusion in each tumor, the signals of the tumors on DW-MRI were analyzed subjectively and the apparent diffusion coefficient (ADC) values and histograms assessed objectively. Thirty-three of 36 CCRCC (92%) exhibited a heterogeneous signal on DW-MRI and several peaks in the ADC value histogram, whereas four of five MFAML exhibited a homogeneous signal on DW-MRI and a single prominent peak in the histogram. The standard deviations of the ADC values were significantly smaller for MFAML than for CCRCC (P=0.0015). In conclusion, DW-MRI can be considered a useful and noninvasive addition to the preoperative differentiation of CCRCC and MFAML. (author)

  9. α/β-Hydrolase Domain 6 Deletion Induces Adipose Browning and Prevents Obesity and Type 2 Diabetes.

    Science.gov (United States)

    Zhao, Shangang; Mugabo, Yves; Ballentine, Gwynne; Attane, Camille; Iglesias, Jose; Poursharifi, Pegah; Zhang, Dongwei; Nguyen, Thuy Anne; Erb, Heidi; Prentki, Raphael; Peyot, Marie-Line; Joly, Erik; Tobin, Stephanie; Fulton, Stephanie; Brown, J Mark; Madiraju, S R Murthy; Prentki, Marc

    2016-03-29

    Suppression of α/β-domain hydrolase-6 (ABHD6), a monoacylglycerol (MAG) hydrolase, promotes glucose-stimulated insulin secretion by pancreatic β cells. We report here that high-fat-diet-fed ABHD6-KO mice show modestly reduced food intake, decreased body weight gain and glycemia, improved glucose tolerance and insulin sensitivity, and enhanced locomotor activity. ABHD6-KO mice also show increased energy expenditure, cold-induced thermogenesis, brown adipose UCP1 expression, fatty acid oxidation, and white adipose browning. Adipose browning and cold-induced thermogenesis are replicated by the ABHD6 inhibitor WWL70 and by antisense oligonucleotides targeting ABHD6. Our evidence suggests that one mechanism by which the lipolysis derived 1-MAG signals intrinsic and cell-autonomous adipose browning is via PPARα and PPARγ activation, and that ABHD6 regulates adipose browning by controlling signal competent 1-MAG levels. Thus, ABHD6 regulates energy homeostasis, brown adipose function, and white adipose browning and is a potential therapeutic target for obesity and type 2 diabetes. PMID:26997277

  10. 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. PMID:26167418

  11. Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress

    Science.gov (United States)

    Fat-specific protein 27 (FSP27), a member of the cell death-inducing DNA fragmentation factor a-like effector (Cide) family, is highly expressed in adipose tissues and is a lipid droplet (LD)-associated protein that induces the accumulation of LDs. Using a yeast two-hybrid system to examine potentia...

  12. Identification of ABCA1 and ABCG1 in milk fat globules and mammary cells - Implications for milk cholesterol secretion

    DEFF Research Database (Denmark)

    Mani, O; Körner, M; Ontsouka, C E;

    2011-01-01

    test whether 1) ABCA1 and ABCG1 protein expression and subcellular localization in mammary epithelial cells (MEC) change during the pregnancy-lactation cycle, and 2) these 2 proteins were present in milk fat globules (MFG). Expression and localization in MEC were investigated in bovine MG tissues at...

  13. Fucoidans from brown seaweeds

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Meyer, Anne S.

    2013-01-01

    -proliferative effects on cancer cells. Recent work has revealed distinct structural features of fucoidans obtained from different brown seaweed sources. Fucoidans are classically obtained from brown seaweeds by multi-step, hot acid extraction, but the structural and compositional traits, and possibly the bioactivity......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......, of the fucoidan polysaccharides are significantly influenced by the extraction parameters. This review discusses the structural features of fucoidans, the significance of different extraction technologies, and reviews enzymatic degradation of fucoidans and the use of fucoidan-modifying enzymes for...

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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...

  1. 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

  2. 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...

  3. 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...

  4. 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.

  5. 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.

  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. 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.

  8. 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.

  9. Lecithin:Cholesterol Acyltransferase (LCAT) Deficiency Promotes Differentiation of Satellite Cells to Brown Adipocytes in a Cholesterol-dependent Manner.

    Science.gov (United States)

    Nesan, Dinushan; Tavallaee, Ghazaleh; Koh, Deborah; Bashiri, Amir; Abdin, Rawand; Ng, Dominic S

    2015-12-18

    Our laboratory previously reported that lecithin:cholesterol acyltransferase (LCAT) and LDL receptor double knock-out mice (Ldlr(-/-)xLcat(-/-) or DKO) spontaneously develop functioning ectopic brown adipose tissue (BAT) in skeletal muscle, putatively contributing to protection from the diet-induced obesity phenotype. Here we further investigated their developmental origin and the mechanistic role of LCAT deficiency. Gene profiling of skeletal muscle in DKO newborns and adults revealed a classical lineage. Primary quiescent satellite cells (SC) from chow-fed DKO mice, not in Ldlr(-/-)xLcat(+/+) single-knock-out (SKO) or C57BL/6 wild type, were found to (i) express exclusively classical BAT-selective genes, (ii) be primed to express key functional BAT genes, and (iii) exhibit markedly increased ex vivo adipogenic differentiation into brown adipocytes. This gene priming effect was abrogated upon feeding the mice a 2% high cholesterol diet in association with accumulation of excess intracellular cholesterol. Ex vivo cholesterol loading of chow-fed DKO SC recapitulated the effect, indicating that cellular cholesterol is a key regulator of SC-to-BAT differentiation. Comparing adipogenicity of Ldlr(+/+)xLcat(-/-) (LCAT-KO) SC with DKO SC identified a role for LCAT deficiency in priming SC to express BAT genes. Additionally, we found that reduced cellular cholesterol is important for adipogenic differentiation, evidenced by increased induction of adipogenesis in cholesterol-depleted SC from both LCAT-KO and SKO mice. Taken together, we conclude that ectopic BAT in DKO mice is classical in origin, and its development begins in utero. We further showed complementary roles of LCAT deficiency and cellular cholesterol reduction in the SC-to-BAT adipogenesis. PMID:26494623

  10. 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.

  11. 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

  12. 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...... individuals, separated into 4 subgroups according to gender and insulin sensitivity/resistance. Adipose cell-size distribution changes in each individual are simulated with a dynamic model and parameters corresponding to lipid turnover and cell growth rates are determined for each subgroup to match the...... relative change of fat mass for each diet composition, respectively. We find that adipose cell-size dynamics are associated with different modulations dependent on gender and insulin resistance. Larger turnover and growth/shrinkage rates in insulin resistant individuals suggest they may be more sensitive...

  13. 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...

  14. 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...

  15. 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 ra...

  16. 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.

  17. 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...

  18. 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

  19. 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.

  20. 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...

  1. 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

  2. Cannabidiol promotes browning in 3T3-L1 adipocytes.

    Science.gov (United States)

    Parray, Hilal Ahmad; Yun, Jong Won

    2016-05-01

    Recruitment of the brown-like phenotype in white adipocytes (browning) and activation of existing brown adipocytes are currently being investigated as a means to combat obesity. Thus, a wide variety of dietary agents that contribute to browning of white adipocytes have been identified. The present study was designed to investigate the effects of cannabidiol (CBD), a major nonpsychotropic phytocannabinoid of Cannabis sativa, on induction of browning in 3T3-L1 adipocytes. CBD enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cited1, Tmem26, Prdm16, Cidea, Tbx1, Fgf21, and Pgc-1α) and proteins (UCP1, PRDM16, and PGC-1α). Increased expression of UCP1 and other brown fat-specific markers contributed to the browning of 3T3-L1 adipocytes possibly via activation of PPARγ and PI3K. In addition, CBD increased protein expression levels of CPT1, ACSL, SIRT1, and PLIN while down-regulating JNK2, SREBP1, and LPL. These data suggest possible roles for CBD in browning of white adipocytes, augmentation of lipolysis, thermogenesis, and reduction of lipogenesis. In conclusion, the current data suggest that CBD plays dual modulatory roles in the form of inducing the brown-like phenotype as well as promoting lipid metabolism. Thus, CBD may be explored as a potentially promising therapeutic agent for the prevention of obesity. PMID:27067870

  3. 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

  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. Partial characterization and clinical correlation of circulating human immunoglobulins directed against thyrotrophin binding sites in guinea pig fat cell membranes. Development of a direct enzyme immunoassay.

    OpenAIRE

    Baker, J. R.; Lukes, Y G; Smallridge, R.C.; Berger, M.; Burman, K. D.

    1983-01-01

    To obviate several problems inherent in indirect thyroid-stimulating hormone (TSH) receptor antibody assays, we developed an enzyme-linked immunosorbent assay (ELISA) that measures antibodies binding to guinea pig fat cell membrane, which contain high concentrations of TSH receptors. Solubilized guinea pig fat cell membranes were adsorbed to plastic microtiter plates and served as the solid-phase antigen. Test sera and affinity-purified alkaline phosphatase-conjugated anti-human IgG were co-i...

  6. 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.

  7. Differential requirement for utrophin in the induced pluripotent stem cell correction of muscle versus fat in muscular dystrophy mice.

    Directory of Open Access Journals (Sweden)

    Amanda J Beck

    Full Text Available Duchenne muscular dystrophy (DMD is an incurable degenerative muscle disorder. We injected WT mouse induced pluripotent stem cells (iPSCs into mdx and mdx∶utrophin mutant blastocysts, which are predisposed to develop DMD with an increasing degree of severity (mdx <<< mdx∶utrophin. In mdx chimeras, iPSC-dystrophin was supplied to the muscle sarcolemma to effect corrections at morphological and functional levels. Dystrobrevin was observed in dystrophin-positive and, at a lesser extent, utrophin-positive areas. In the mdx∶utrophin mutant chimeras, although iPSC-dystrophin was also supplied to the muscle sarcolemma, mice still displayed poor skeletal muscle histopathology, and negligible levels of dystrobrevin in dystrophin- and utrophin-negative areas. Not only dystrophin-expressing tissues are affected by iPSCs. Mdx and mdx∶utrophin mice have reduced fat/body weight ratio, but iPSC injection normalized this parameter in both mdx and mdx∶utrophin chimeras, despite the fact that utrophin was compromised in the mdx∶utrophin chimeric fat. The results suggest that the presence of utrophin is required for the iPSC-corrections in skeletal muscle. Furthermore, the results highlight a potential (utrophin-independent non-cell autonomous role for iPSC-dystrophin in the corrections of non-muscle tissue like fat, which is intimately related to the muscle.

  8. Insulin resistance and beta-cell function in different ethnic groups in Kenya: the role of abdominal fat distribution.

    Science.gov (United States)

    Christensen, D L; Faurholt-Jepsen, D; Faerch, K; Mwaniki, D L; Boit, M K; Kilonzo, B; Tetens, I; Friis, H; Borch-Johnsen, K

    2014-02-01

    Little is known about the pathophysiology of diabetes in Africans. Thus, we assessed whether insulin resistance and beta-cell function differed by ethnicity in Kenya and whether differences were modified by abdominal fat distribution. A cross-sectional study in 1,087 rural Luo (n = 361), Kamba (n = 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 by computer model, early phase insulin secretion, and disposition index (DI) dividing insulin secretion by insulin resistance. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) thickness were carried out by ultrasonography. Linear regression analyses were done to assess ethnic differences in insulin indices. The Maasai had 32 and 17% higher insulin resistance than the Luo and Kamba, respectively (p Maasai compared to the Luo (p Maasai 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 relative beta-cell function compared to the Luo and Kamba. These differences were primarily explained by abdominal fat distribution. PMID:23563691

  9. 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....

  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. 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

  12. 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...

  13. 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...

  14. Supplementation of fat grafts with adipose-derived regenerative cells in reconstructive surgery [Stammzellangereicherte Fetttransplantation in der rekonstruktiven Chirurgie

    Directory of Open Access Journals (Sweden)

    Herold, C.

    2012-09-01

    Full Text Available [english] Introduction: The fraction of regenerative cells in adipose tissue has been described to be even higher than in bone marrow. Adipose tissue itself is excessively available in most patients. Given that adipose tissue is abundant in majority of patients adipose derrived stem cells (ASCs have come under scrutiny for regenerative procedures in reconstructive surgery.Material and methods: ASCs were extracted by the Celution system for enrichment of fat grafts that were administered in patients with decreased wound healing, soft tissue or scar defects.Results: All patients were satisfied after reconstruction with ASCs augmented fat grafts and no side effects were observed. Discussion: The Celution system provides fast recovery of ASCs which can be immediately utilized for appropriate application. Since a high number of stem cells are harvested from fat tissue no expansion of cells is needed as described for bone marrow derived stem cells. Enrichment of fat graft with ASCs is of great interest due to their reported angiogenetic effect. The reported cases demonstrate the potential of ASCs in the field of regenerative medicine and encourage further application in reconstructive surgery.[german] Einleitung: Es konnte gezeigt werden, dass der Anteil regenerativer Zellen im Fettgewebe höher als im Knochenmark ist. Fettgewebe hingegen ist bei den meisten Patienten exzessiv vorhanden. Das legt den Einsatz von ASCs (adipose derived stem cells bei regenerativen Anwendungen in der rekonstruktiven Chirurgie nahe.Material und Methoden: Mit dem Celution System von Cytori Therapeutics Inc. prozessierte, ASC angereicherte Fetttransplantate werden an vier Patienten mit Weichteildefiziten und störenden Narben sowie Wundheilungsstörungen angewendet.Ergebnisse: Insbesondere bei Patienten mit Weichteildefiziten und Narben konnte eine suffiziente Volumenaugmentation und ansprechende Verbesserung der Narben erzielt werden. Es wurden keine Nebenwirkungen

  15. Prevalence of Endogenous CD34+ Adipose Stem Cells Predicts Human Fat Graft Retention in a Xenograft Model

    Science.gov (United States)

    Philips, Brian J.; Grahovac, Tara L.; Valentin, Jolene E.; Chung, Christopher W.; Bliley, Jacqueline M.; Pfeifer, Melanie E.; Roy, Sohini B.; Dreifuss, Stephanie; Kelmendi-Doko, Arta; Kling, Russell E.; Ravuri, Sudheer K.; Marra, Kacey G.; Donnenberg, Vera S.; Donnenberg, Albert D.; Rubin, J. Peter

    2014-01-01

    Background Fat grafting is a promising technique for soft-tissue augmentation, although graft retention is highly unpredictable and factors that affect graft survival have not been well defined. Because of their capacity for differentiation and growth factor release, adipose-derived stem cells may have a key role in graft healing. The authors’ objective was to determine whether biological properties of adipose-derived stem cells present within human fat would correlate with in vivo outcomes of graft volume retention. Methods Lipoaspirate from eight human subjects was processed using a standardized centrifugation technique and then injected subcutaneously into the flanks of 6-week-old athymic nude mice. Graft masses and volumes were measured, and histologic evaluation, including CD31+ staining for vessels, was performed 8 weeks after transplantation. Stromal vascular fraction isolated at the time of harvest from each subject was analyzed for surface markers by multi-parameter flow cytometry, and also assessed for proliferation, differentiation capacity, and normoxic/hypoxic vascular endothelial growth factor secretion. Results Wide variation in percentage of CD34+ progenitors within the stromal vascular fraction was noted among subjects and averaged 21.3 ± 15 percent (mean ± SD). Proliferation rates and adipogenic potential among stromal vascular fraction cells demonstrated moderate interpatient variability. In mouse xenograft studies, retention volumes ranged from approximately 36 to 68 percent after 8 weeks, with an overall average of 52 ± 11 percent. A strong correlation (r = 0.78, slope = 0.76, p < 0.05) existed between stromal vascular fraction percentage of CD34+ progenitors and high graft retention. Conclusion Inherent biological differences in adipose tissue exist between patients. In particular, concentration of CD34+ progenitor cells within the stromal vascular fraction may be one of the factors used to predict human fat graft retention. (Plast

  16. 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

  17. 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.

  18. 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. PMID:25224322

  19. 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)

  20. 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

  1. 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...

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

    OpenAIRE

    Rocha H.A.O.; Franco C.R.C.; Trindade E.S.; Carvalho L.C.M.; Veiga S.S.; Leite E.L.; Dietrich C.P.; Nader H.B.

    2001-01-01

    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 p...

  3. Brown Adipose Tissue Growth and Development

    Directory of Open Access Journals (Sweden)

    Michael E. Symonds

    2013-01-01

    Full Text Available 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.

  4. Iron deposition in cranial bone marrow with sickle cell disease: MR assessment using a fat suppression technique

    International Nuclear Information System (INIS)

    Thirteen patients with sickle cell disease (SCD) undergoing transfusion therapy and 8 control patients were examined by magnetic resonance imaging to discriminate bone marrow change due to iron deposition from hematologic marrow hyperplasia. Using T1-weighted spin echo images, only two subjects showed extremely low signal intensity marrow compatible with iron deposition. However, using T2-weighted fast spin echo images with fat suppression, cranial bone marrow in SCD patients with transfusion therapy showed considerably lower signal than that of controls. The main cause of marrow signal decrease in SCD patients with transfusion therapy was considered to be iron deposition due to repeated transfusion therapy rather than red marrow hyperplasia. (orig.)

  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. Self-Assembled Infrapatellar Fat-Pad Progenitor Cells on a Poly-ε-Caprolactone Film For Cartilage Regeneration.

    Science.gov (United States)

    Prabhakar, Alisha; Lynch, Amy P; Ahearne, Mark

    2016-04-01

    Cartilage defects resulting from osteoarthritis (OA) or physical injury can severely reduce the quality of life for sufferers. Current treatment options are costly and not always effective in producing stable hyaline cartilage. Here we investigated a new treatment option that could potentially repair and regenerate damaged cartilage tissue. This novel approach involves the application of infrapatellar fat-pad derived chondroprogenitor cells onto a mechanically stable biodegradable polymer film that can be easily implanted into a defect site. Poly-ε-caprolactone (PCL) films were fabricated via solvent casting in either acetone or chloroform. The hydrophobicity, mechanical properties, and surface morphology of the films were examined. Progenitor cells from infrapatellar fat-pad were isolated, expanded, and then seeded onto the films. The cells were allowed to self-assemble on films, and these were then cultured in a chemically defined chondrogenic media for 28 days. The self-assembled tissue was characterized via histological staining, gene expression analysis, immunohistochemistry, and biochemical analysis. Chondrogenic differentiation was induced to generate a cartilaginous matrix upon the films. Despite differences between in the appearance, surface morphology, and mechanical properties of the films cast in chloroform or acetone, both methods produced tissues rich in sulfated glycosaminoglycan and collagen, although the extracellular matrix produced on chloroform-cast films appeared to contain more collagen type II and less collagen type I than acetone-cast films. These self-assembled constructs have the potential to be implanted into defect sites as a potential treatment for cartilage defect regeneration. PMID:26516689

  7. 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。

  8. Inhibition of Sam68 triggers adipose tissue browning.

    Science.gov (United States)

    Zhou, Junlan; Cheng, Min; Boriboun, Chan; Ardehali, Mariam M; Jiang, Changfei; Liu, Qinghua; Han, Shuling; Goukassian, David A; Tang, Yao-Liang; Zhao, Ting C; Zhao, Ming; Cai, Lu; Richard, Stéphane; Kishore, Raj; Qin, Gangjian

    2015-06-01

    Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms that promote energy expenditure can be utilized for effective therapy. Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity. In the present study, we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We first found that Sam68 KO mice have a significantly reduced body weight as compared to controls, and the difference is explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake; rather, they were associated with enhanced physical activity. When they were fed a high-fat diet, Sam68 KO mice gained much less body weight and fat mass than their WT littermates did, and they displayed an improved glucose and insulin tolerance. In Sam68 KO mice, the brown adipose tissue (BAT), inguinal, and epididymal depots were smaller, and their adipocytes were less hypertrophied as compared to their WT littermates. The BAT of Sam68 KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty acid oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68 KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16, and Ppargc1a genes was greater as compared to WT controls, which suggests that the loss of Sam68 also promotes WAT browning. Furthermore, in all of the fat depots of the Sam68 KO mice, the expression of M2 macrophage markers was up-regulated, and that of M1 markers was down-regulated. Thus, Sam68 plays a crucial role in controlling thermogenesis and may be targeted to combat obesity and associated disorders. PMID:25934704

  9. 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

  10. 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

  11. 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

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

    International Nuclear Information System (INIS)

    Highlights: ► Proliferating Cell Nuclear Antigen (PCNA) is phosphorylated at Y114. ► Phospho-Y114 of PCNA is not required for cell proliferation for normal growth. ► MCE during adipogenesis is abolished in the lack of the phosphorylation. ► Homozygous Y114F mice are resistant to high fat diet induced obesity. ► 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 (PCNAF/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, PCNAF/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 mice contain significantly more adipocytes than those isolated from PCNAF/F mice. This study identifies a critical role for PCNA in adipose

  13. 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.

  14. 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...

  15. Regulation of gene expression by FSP27 in white and brown adipose tissue

    OpenAIRE

    Xue Bofu; Wang Yue; Zhou Linkang; Xu Li; Zhang Yinxin; Li(李, Li, 莉); Wen Zilong; Li Peng; Sang Jianli

    2010-01-01

    Abstract Background Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. The mouse Fat-Specific protein 27 (FSP27), a member of the cell death-inducing DFF45-like effector (CIDE) family, is expressed in both BAT and WAT and is associated with lipid droplets. Over-expression of FSP27 promotes lipid storage, whereas FSP27 deficient mice have improved insulin sensitivity and are resistant to diet-induc...

  16. 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.

  17. 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。

  18. Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol

    International Nuclear Information System (INIS)

    Uptake in brown adipose tissue (hibernating fat) is sometimes seen at FDG-PET examinations. Despite a characteristic appearance, this may hide clinically relevant uptake. Stimulation of the sympathetic nervous system increases glucose uptake of brown fat. We now re-examine patients with brown fat activity that could disguise tumour uptake after pre-treatment with propranolol (a non-selective β-blocker) in order to reduce the uptake. Our first examinations of this kind are reported. Eleven patients with strong brown fat uptake were studied. There was a mean of 5 days (range 2-8) between the examinations. At the second examination, 80 mg of propranolol was given orally 2 h before FDG administration. In addition to visual evaluation of the brown fat uptake, SUV assessments of the uptake in brown fat, lung, heart, liver, spleen and bone marrow were made. All patients showed complete or almost complete disappearance of the brown fat activity at the second examination (p < 0.001) both upon visual evaluation and when comparing SUVs. In seven patients there was also uptake in a known or strongly suspected malignancy, which remained unchanged between the examinations. Beyond an insignificant decrease in the myocardial uptake, there was no redistribution to the various examined organs at the second examination. Pre-treatment with a single dose of propranolol blocks the FDG uptake in brown adipose tissue, thereby increasing the specificity of the examination. The tumour uptake seems not to be impaired. (orig.)

  19. 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. PMID:26995134

  20. 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.

  1. 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.

  2. Salsalate activates brown adipose tissue in mice.

    Science.gov (United States)

    van Dam, Andrea D; Nahon, Kimberly J; Kooijman, Sander; van den Berg, Susan M; Kanhai, Anish A; Kikuchi, Takuya; Heemskerk, Mattijs M; van Harmelen, Vanessa; Lombès, Marc; van den Hoek, Anita M; de Winther, Menno P J; Lutgens, Esther; Guigas, Bruno; Rensen, Patrick C N; Boon, Mariëtte R

    2015-05-01

    Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We found that salsalate attenuated and reversed high-fat diet-induced weight gain, in particular fat mass accumulation, improved glucose tolerance, and lowered plasma triglyceride levels. Mechanistically, salsalate selectively promoted the uptake of fatty acids from glycerol tri[(3)H]oleate-labeled lipoprotein-like emulsion particles by brown adipose tissue (BAT), decreased the intracellular lipid content in BAT, and increased rectal temperature, all pointing to more active BAT. The treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by the inhibition of cAMP-dependent protein kinase (PKA). In conclusion, salsalate activates BAT, presumably by directly activating brown adipocytes via the PKA pathway, suggesting a novel mechanism that may explain its beneficial metabolic effects in type 2 diabetes patients. PMID:25475439

  3. 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.

  4. 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

  5. A role of active brown adipose tissue in cancer cachexia?

    OpenAIRE

    Emiel Beijer; Janna Schoenmakers; Guy Vijgen; Fons Kessels; Anne-Marie Dingemans; Patrick Schrauwen; Miel Wouters; Wouter van Marken Lichtenbelt; Jaap Teule; Boudewijn Brans

    2012-01-01

    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 activ...

  6. 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...

  7. Age and Sex Mediated Changes in Epicardial Fat Adipokines

    OpenAIRE

    Fei, Jia; Cook, Carla; BLOUGH, ERIC; Santanam, Nalini

    2010-01-01

    Aging, which is an independent risk factor for heart disease, alters body fat mass and its function. Epicardial fat plays an important physiological and pathophysiological role on cardiac structure and function. This study investigated if aging altered the abundance of epicardial (EF) and abdominal fat (AF) derived mediators in a sex dependent manner in female and male Fischer 344 × Brown Norway hybrid (FBN) rats. EF and AF were obtained from 48 female and male, young (6 months), aged (26/30 ...

  8. 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

  9. Injectable cell/hydrogel microspheres induce the formation of fat lobule-like microtissues and vascularized adipose tissue regeneration

    International Nuclear Information System (INIS)

    In this paper, we demonstrated that collagen/alginate microspheres could be generated by a non-contact microfabrication device and serve as excellent cell embedding and delivery devices as they were porous, injectable and able to provide growth- and differentiation-supporting matrix for human adipose-derived stem cells (hASCs). The microsphere matrix demonstrated highly porous structure and mechanical stability for as long as 90 days. hASCs demonstrated high viability after microsphere formation as well as higher proliferation and more mature adipocytes induction compared to two-dimensional culture. After four weeks culture in adipogenic differentiation medium, adipocytes/collagen/alginate microspheres highly mimicking natural fat lobules were obtained and injected subcutaneously into the head of node mice. The in vivo study demonstrated vascularized adipose tissue formation in four weeks. The regenerated vasculature among the transplantation showed functional anastomosis with host vasculature, suggesting that these cell/hydrogel microspheres present injectable adipocytes delivery devices capable of generating vascularized adipose tissue in vivo and thus suitable for cell transplantation and tissue regeneration. (paper)

  10. 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.

  11. 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.

  12. 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.

  13. 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¿

  14. 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 ...

  15. Brown Adipose Tissue: A New Target for Antiobesity Therapy

    OpenAIRE

    Anna Meiliana; Andi Wijaya

    2010-01-01

    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 conc...

  16. Browning of white adipose tissue: role of hypothalamic signaling

    OpenAIRE

    Bi, Sheng; Li, Lin

    2013-01-01

    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 non-shivering 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 obse...

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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...

  2. Role of Vascular Endothelial Growth Factor Signaling in Brown Adipocyte Survival, Proliferation and Function

    OpenAIRE

    Bagchi, Mandrita

    2012-01-01

    Both white and brown adipose tissues exhibit extensive vascularity. Increased angiogenesis in brown adipose tissue (BAT) is crucial for brown fat activation and thermogenesis in animals during cold acclimation. BAT can be similarly activated by food intake to generate heat through cellular respiration, in a process known as diet induced thermogenesis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that regulates both pathological and physiological angiogenesis and can...

  3. Isolation and differentiation of stromal vascular cells to beige/brite cells

    DEFF Research Database (Denmark)

    Aune, Ulrike Liisberg; Ruiz, Lauren; Kajimura, Shingo

    2013-01-01

    cold exposure or by PPARγ agonists, therefore, this cell type has potential as a therapeutic target for obesity treatment. Although most immortalized adipocyte lines cannot recapitulate the process of "browning" of white fat in culture, primary adipocytes isolated from stromal vascular fraction in...... subcutaneous white adipose tissue (WAT) provide a reliable cellular system to study the molecular control of beige/brite cell development. Here we describe a protocol for effective isolation of primary preadipocytes and for inducing differentiation to beige/brite cells in culture. The browning effect can be...

  4. 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.

  5. 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...

  6. 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 ...

  7. 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...

  8. 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

  9. Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage.

    Science.gov (United States)

    Singh, Lakshman; Brennan, Tracy A; Russell, Elizabeth; Kim, Jung-Hoon; Chen, Qijun; Brad Johnson, F; Pignolo, Robert J

    2016-04-01

    Bone marrow derived mesenchymal progenitor cells (MPCs) play an important role in bone homeostasis. Age-related changes occur in bone resulting in a decrease in bone density and a relative increase in adipocity. Although in vitro studies suggest the existence of an age-related lineage switch between osteogenic and adipogenic fates, stem cell and microenvironmental contributions to this process have not been elucidated in vivo. In order to study the effects of MPC and microenvironmental aging on functional engraftment and lineage switching, transplantation studies were performed under non-myeloablative conditions in old recipients, with donor MPCs derived from young and old green fluorescent protein (GFP) transgenic mice. Robust engraftment by young MPCs or their progeny was observed in the marrow, bone-lining region and in the matrix of young recipients; however, significantly lower engraftment was seen at the same sites in old recipients transplanted with old MPCs. Differentiation of transplanted MPCs strongly favored adipogenesis over osteogenesis in old recipients irrespective of MPC donor age, suggesting that microenvironmental alterations that occur with in vivo aging are predominately responsible for MPC lineage switching. These data indicate that aging alters bone-fat reciprocity and differentiation of mesenchymal progenitors towards an adipogenic fate. PMID:26805026

  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

    2016-01-01

    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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Fat burn X: burning more than fat.

    Science.gov (United States)

    Hannabass, Kyle; Olsen, Kevin Robert

    2016-01-01

    A 50-year-old man presented with a 2-day history of bilateral lower extremity cramping and dark urine. The patient was found to have a creatine phosphokinase (CPK) elevated of up to 2306 U/L, a serum uric acid of 9.7 mg/dL and 101 red blood cell's per high-powered field on urinalysis. On questioning, the patient endorsed daily exercise with free weights. There were no changes in his regular exercise and medication regimen, no muscle trauma, no recent drug use and no illness. The patient did mention using a new fat burner known as 'Fat Burn X', which he had begun taking 2 days prior to the onset of his muscle cramps. The patient was given normal saline intravenous fluid resuscitation for 48 h with resultant normalisation of his CPK and creatinine, and was discharged with primary care follow-up. PMID:26811412

  16. 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.)

  17. 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.)

  18. 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

  19. Saturated fat (image)

    Science.gov (United States)

    ... saturated fats. Vegetable sources of saturated fat include coconut and palm oils. When looking at a food ... saturated fats. Vegetable sources of saturated fat include coconut and palm oils. When looking at a food ...

  20. 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

  1. 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...

  2. The effect of an alendronate-eluting titanium system to induce osteogenic differentiation in human buccal fat cells (HBFCs)

    Science.gov (United States)

    Kim, Sung Eun; Lee, Su-Young; Yun, Young-Pil; Lee, Jae Yong; Park, Kyeongsoon; Lee, Deok-Won; Song, Hae-Ryong

    2012-10-01

    The purpose of this study was to develop alendronate (Aln)-eluting Ti substrates to induce osteogenic differentiation of human buccal fat cells (HBFCs). The surface of pristine Ti was modified by dopamine (DOPA) and then heparin was grafted onto the aminated Ti surfaces to achieve the Aln-eluting Ti system. Aln was subsequently immobilized on the surface of heparinized Ti (Hep-Ti). Pristine Ti and surface-modified-Ti were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle. Osteogenic differentiation of HBFCs on the surface of pristine-Ti, Hep-Ti, Aln (1 mg)/Hep-Ti, and Aln (5 mg)/Hep-Ti was demonstrated by alkaline phosphatase (ALP) activity, calcium deposition, and osteocalcin and osteopontin mRNA expression. Successful immobilization of Aln on Hep-Ti was confirmed by XPS and contact angle. Aln/Hep-Ti showed the sustained release for up to 28 days. Additionally, HBFCs cultured on Aln/Hep-Ti substrates showed significantly induced ALP activity, calcium deposition, and osteocalcin and osteopontin mRNA expression. These results suggest that Aln-eluting Ti substrates have a potential effect on osteogenic differentiation of HBFCs and will be a promising material for bone regeneration.

  3. Effect of the slow (K or rapid (k+ feathering gene on body and feather growth and fatness according to ambient temperature in a Leghorn × brown egg type cross

    Directory of Open Access Journals (Sweden)

    Bordas André

    2001-11-01

    Full Text Available Abstract Chicks of both sexes issued from the cross of heterozygous K/k+ cocks for the slow-feathering sex linked K allele with k+ (rapid feathering hens, were compared from the age of 4 to 10 weeks at two ambient temperatures. In individual cages, 30 male chicks of each genotype (K/k+ and k+/k+ were raised at 21°C, and 60 others, distributed in the same way, were raised at 31°C. 71 K/W females and 69 k+/W females were raised in a floor pen at 31°C till 10 weeks of age. In the males, the body weight, feed consumption and feed efficiency at different ages were influenced only by temperature (lower growth rate and feed intake at 31°C; no significant effects of the genotype at locus K nor genotype × temperature interaction were observed. In females, all at 31°C, the genotype (K/W or k+/W had no significant effect on growth rate. Plumage weight and weight of abdominal fat (absolute or related to body weight were measured on half of the males of each group in individual cages, at 10 weeks of age. Moreover, on 36 males and 48 females of the two genotypes, in a group battery at 31°C, the absolute and relative weight of plumage were measured on a sample every two weeks between 4 and 10 weeks. In the first case, no significant effect of genotype appeared. In the second case, an interaction between age and genotype was suggested from plumage weight: its growth, especially in male chicks, appears to be temporarily and unexpectedly faster from 4 to 6 weeks of age for the K/k+ and K/W genotypes.

  4. 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...

  5. 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

  6. 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

  7. 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

  8. 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.

  9. Dichoptic perception of brown.

    Science.gov (United States)

    DeLawyer, Tanner; Morimoto, Takuma; Buck, Steven L

    2016-03-01

    Two experiments assessed mechanisms underlying brown induction by presenting a foveal target disk and concentric annular surround stimuli that varied in contrast relative to larger backgrounds. Stimuli were presented under monocular, binocular, and dichoptic viewing conditions. Observers adjusted the luminance of the target disk to a criterion brown level. We found evidence for at least two separate mechanisms for brown induction: one mechanism that is dependent on physically contiguous contrast and operates in monocular pathways and another mechanism that responds to high luminance contrast anywhere in the visual field and can operate after convergence of signals from the two eyes. PMID:26974916

  10. 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...

  11. Mesotherapy for local fat reduction.

    Science.gov (United States)

    Jayasinghe, S; Guillot, T; Bissoon, L; Greenway, F

    2013-10-01

    Mesotherapy, which is the injection of substances locally into mesodermally derived subcutaneous tissue, developed from empirical observations of a French physician in the 1950s. Although popular in Europe for many medical purposes, it is used for local cosmetic fat reduction in the United States. This paper reviews manuscripts indexed in PubMed/MEDLINE under 'mesotherapy', which pertains to local fat reduction. The history of lipolytic mesotherapy, the physiology of body fat distribution, the mechanism of action of different lipolytic stimulators and their increased efficacy in combination are reviewed. Mesotherapy falls into two categories. Lipolytic mesotherapy using lipolytic stimulators requires more frequent treatments as the fat cells are not destroyed and can refill over time. Ablative mesotherapy destroys fat cells with a detergent, causes inflammation and scarring from the fat necrosis, but requires fewer treatments. The historic and empiric mixing of sodium channel blocking local anaesthetics in mesotherapy solutions inhibits the intended lipolysis. Major mesotherapy safety concerns include injection site infections from poor sterile technique. Cosmetic mesotherapy directs the area from which fat is lost to improve self-image. Studies were of relatively small number, many with limited sample sizes. Future research should be directed towards achieving a Food and Drug Administration indication rather than continuing expansion of off-label use. PMID:23800269

  12. Aqueous extracts of the marine brown alga Lobophora variegata inhibit HIV-1 infection at the level of virus entry into cells.

    Directory of Open Access Journals (Sweden)

    Stephan Kremb

    Full Text Available 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. 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.

  14. Insulin rapidly stimulates phosphorylation of a 46-kDa membrane protein on tyrosine residues as well as phosphorylation of several soluble proteins in intact fat cells

    International Nuclear Information System (INIS)

    It is speculated that the transmission of an insulin signal across the plasma membrane of cells occurs through activation of the tyrosine-specific receptor kinase, autophosphorylation of the receptor, and subsequent phosphorylation of unidentified substrates in the cell. In an attempt to identify possible substrates, the authors labeled intact rat fat cells with [32P]orthophosphate and used an antiphosphotyrosine antibody to identify proteins that become phosphorylated on tyrosine residues in an insulin-stimulated way. In the membrane fraction of the fat cells, they found, in addition to the 95-kDa β-subunit of the receptor, a 46-kDa phosphoprotein that is phosphorylated exclusively on tyrosine residues. This protein is not immunoprecipitated by antibodies against different regions of the insulin receptor and its HPLC tryptic peptide map is different from the tryptic peptide map of the insulin receptor, suggesting that it is not derived from the receptor β-subunit. Insulin stimulates the tyrosine phosphorylation of the 46-kDa protein within 150 sec in the intact cell 3- to 4-fold in a dose-dependent way at insulin concentrations between 0.5 nM and 100 nM. Insulin (0.5 nM, 100 nM) stimulated within 2 min the 32P incorporation into a 116-kDa band, a 62 kDa band, and three bands between 45 kDa and 50 kDa 2- to 10-fold. They suggest that the 46-kDa membrane protein and possibly also the soluble proteins are endogenous substrates of the receptor tyrosine kinase in fat cells and that their phosphorylation is an early step in insulin signal transmission

  15. 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...

  16. 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.

  17. 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

  18. 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...

  19. 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

  20. 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.

  1. Have we entered the brown adipose tissue renaissance?

    OpenAIRE

    Ravussin, E.; Kozak, L P

    2009-01-01

    In the 1970s and 1980s, it was observed that rodents could offset excess calories ingested when they were fed a human-like `cafeteria diet'. Although it was erroneously concluded that this so-called diet-induced thermogenesis was because of brown adipose tissue (BAT), it led to efforts to test whether variations in brown fat in humans may explain the susceptibility to obesity. However, from evidence on the inability of ephedrine or beta-3 adrenergic agonists to induce BAT thermogenesis, it wa...

  2. Estimation of genetic parameters for individual udder quarter milk content traits in Brown Swiss cattle.

    Science.gov (United States)

    Kramer, M; Erbe, M; Bapst, B; Bieber, A; Simianer, H

    2013-09-01

    The aim of this study was to estimate genetic parameters and accuracies of breeding values for milk content traits of individual udder quarters in Brown Swiss cattle. Data of 1,799 phenotyped cows from 40 Swiss dairy herds were analyzed, taking the complete pedigree into account. Fat, protein, lactose, and urea contents, somatic cell score (SCS), and information about hyperkeratosis were available for each udder quarter. The milk of rear udder quarters was found to have significantly higher lactose content and significantly lower fat content than milk of the front udder quarters. The same trend found for fat content was observed for protein content, whereas no differences between the udder quarters were observed for urea content, SCS, or hyperkeratosis. Heritabilities for each udder quarter were in the following ranges: fat content 0.09±0.06 to 0.14±0.06, protein content 0.20±0.09 to 0.33±0.07, lactose content 0.04±0.03 to 0.16±0.07, urea content 0.13±0.07 to 0.22±0.08, SCS 0.18±0.06 to 0.32±0.07, and hyperkeratosis 0.12±0.04 to 0.26±0.05. In our study, hyperkeratosis, protein content, and SCS showed higher heritabilities in the front udder quarters, fat content had higher heritabilities in the rear udder quarters, and no systematic pattern in heritability was observed for lactose content or urea content. Additive genetic correlations between all udder quarters were >0.90 for protein and urea contents, whereas they were remarkably low (traits (lactose content: 0.33±0.05, protein content: 0.53±0.05). Some of these findings can be explained by differences in the physiological background of the traits. PMID:23871376

  3. 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

  4. 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 ...

  5. 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.

  6. Silencing FAT10 inhibits metastasis of osteosarcoma.

    Science.gov (United States)

    Ma, Chengbin; Zhang, Zhiyu; Cui, Yan; Yuan, Hongmou; Wang, Feng

    2016-08-01

    Metastasis is the main challenge of osteosarcoma treatment. Herein, we first reveal the oncogenic role of FAT10 in metastasis of osteosarcoma. FAT10 was upregulated in osteosarcoma, especially in metastatic osteosarcoma. High level of FAT10 was associated with poorer prognosis of osteosarcoma patients. Moreover, Transwell and Matrigel assays revealed that silencing FAT10 significantly inhibited the invasive and migratory abilities of osteosarcoma cells. Metastasis assay in vivo showed that silencing FAT10 decreased the number of mice with distant metastasis. We also found that FAT10 may act its oncogenic functions through regulating HOXB9. Collectively, the results suggested that FAT10 may be a novel therapeutic target for osteosarcoma patients. PMID:27279480

  7. 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.

  8. 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...

  9. 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.

  10. Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting

    DEFF Research Database (Denmark)

    Thankamony, Ajay; Capalbo, Donatella; Marcovecchio, M Loredana;

    2014-01-01

    free fatty acids (P = .028) and β-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014......) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects. CONCLUSIONS: These data suggest that serum IGF-1 levels could be an important marker of β-cell function and glucose as well as lipid metabolic responses during fasting....

  11. A new cell line from the fat body of Spodoptera litura (Lepidoptera, Noctuidae) and detection of lysozyme activity release upon immune stimulation.

    Science.gov (United States)

    Tateishi, Ken; Kasahara, Yuichi; Watanabe, Kazuyo; Hosokawa, Nobuo; Doi, Hiroyasu; Nakajima, Kaori; Adachi, Hayamitsu; Nomoto, Akio

    2015-01-01

    A new cell line, designated NIAS-SL64, was established from the fat body of the fifth instar larvae of the common cutworm Spodoptera litura. NIAS-SL64 cells grew as spindle-shaped and non-adherent cells in the insect-specific cell culture medium MGM-450 supplemented with 10% fetal bovine serum. Criterions for the establishment of the NIAS-SL64 cell line is spindle shape and length (30~90 μm) stabilized after 100 passages. The doubling time of the cells was 24 h at 25°C. Lipopolysaccharide significantly stimulated the release of lysozyme activity by NIAS-SL64 cells. Lysozyme is one of the components of the innate immunity and plays important role as lytic enzyme in infection. Lysozyme activity released from NIAS-SL64 would be a marker for immune response. The released lysozyme activity critically depends on morphology of the cells and would be a criterion of the establishment of the cell line. Lysozyme activity was suppressed in a dose-dependent manner by the immunosuppressive agent cyclosporin A. PMID:25172011

  12. 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.

  13. Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice

    Czech Academy of Sciences Publication Activity Database

    Teodoro, J.S.; Zouhar, Petr; Flachs, Pavel; Bardová, Kristina; Janovská, Petra; Gomes, A.P.; Duarte, F.V.; Varela, A.T.; Rolo, A.P.; Palmeira, C.M.; Kopecký, Jan

    2014-01-01

    Roč. 38, č. 8 (2014), s. 1027-1034. ISSN 0307-0565 R&D Projects: GA MŠk(CZ) 7E12073; GA ČR(CZ) GA13-00871S Institutional support: RVO:67985823 Keywords : white adipose tissue * uncoupling protein 1 * energy expenditure * bile acids Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.004, year: 2014

  14. 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

  15. Acute bone crises in sickle cell disease: the T1 fat-saturated sequence in differentiation of acute bone infarcts from acute osteomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Jain, R. [Department of Radiology, College of Medicine, Sultan Qaboos University, Muscat (Oman)], E-mail: rajeevjn@yahoo.com; Sawhney, S. [Department of Radiology, College of Medicine, Sultan Qaboos University, Muscat (Oman); Rizvi, S.G. [Department of Community Medicine and Public Health, College of Medicine, Sultan Qaboos University, Muscat (Oman)

    2008-01-15

    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

  16. 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.

  17. 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.

  18. 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 ...

  19. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis

    OpenAIRE

    Fisher, ffolliott M.; Kleiner, Sandra; Douris, Nicholas; Fox, Elliott C.; Mepani, Rina J.; Verdeguer, Francisco; Wu, Jun; Kharitonenkov, Alexei; Flier, Jeffrey S.; Maratos-Flier, Eleftheria; Spiegelman, Bruce M.

    2012-01-01

    Brown adipose tissue (BAT) can protect against hypothermia and obesity by using lipids to produce heat. In this study, Spiegelman and colleagues studied FGF21 control of thermogenesis in mice. The authors used gain- and loss-of-function experiments to demonstrate that FGF21 induces a brown fat phenotype in white adipose tissues. In addition, they found that FGF21 is required for the adaptive thermogenic response of mice by increasing PGC-1α protein levels, independent of its transcription. Th...

  20. Destructive fat tissue engineering using photodynamic and selective photothermal effects

    Science.gov (United States)

    Tuchin, Valery V.; Yanina, Irina Yu.; Simonenko, Georgy V.

    2009-02-01

    Destructive fat tissue engineering could be realized using the optical method, which provides reduction of regional or site-specific accumulations of subcutaneous adipose tissue on the cell level. We hypothesize that light irradiation due to photodynamic and selective photothermal effects may lead to fat cell lypolytic activity (the enhancement of lipolysis of cell triglycerides due to expression of lipase activity and cell release of free fat acids (FFAs) due to temporal cell membrane porosity), and cell delayed killing due to apoptosis caused by the induced fat cell stress and/or limited cell necrosis.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Cold–inducible Zfp516 Activates UCP1 Transcription to Promote Browning of White Fat and Development of Brown Fat

    OpenAIRE

    Dempersmier, Jon; Sambeat, Audrey; Gulyaeva, Olga; Paul, Sarah M.; Hudak, Carolyn S. S.; Raposo, Helena F.; Kwan, Hiu-Yee; Kang, Chulho; Wong, Roger H. F.; Sul, Hei Sook

    2015-01-01

    Uncoupling protein 1 (UCP1) mediates non-shivering thermogenesis and, upon cold exposure, is induced in BAT and subcutaneous white adipose tissue (iWAT). Here, by high-throughput screening using the UCP1 promoter, we identify Zfp516 as a novel transcriptional activator of UCP1 as well as PGC1α thereby promoting a BAT program. Zfp516 itself is induced by cold and sympathetic stimulation through the cAMP-CREB/ATF2 pathway. Zfp516 directly binds to the proximal region of the UCP1 promoter, not t...

  9. 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

  10. 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...

  11. 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).

  12. 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)...

  13. 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

  14. 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...... factors now 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...

  15. Genetic Analysis of Brown Adipose Tissue, Obesity and Growth in Mice

    OpenAIRE

    Saxton, A. M.; Eisen, E. J.

    1984-01-01

    The hypothesis developed from single-gene mutant obese rodents that brown adipose tissue (BAT), through its thermogenic ability, is an important factor in the development of obesity, was tested in a randombred population of mice in which degree of adiposity is polygenically determined. Additive direct genetic parameters for measures of body size, lean, fatness and BAT at 6 wk of age were estimated under control and high-fat postweaning dietary regimens. Heritabilities were generally similar f...

  16. 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...

  17. Breaking BAT: can browning create a better white?

    Science.gov (United States)

    Warner, Amy; Mittag, Jens

    2016-01-01

    Obesity and its comorbidities are a growing problem worldwide. In consequence, several new strategies have been proposed to promote weight loss and improve insulin sensitivity. Recently, it has been demonstrated that certain populations of white adipocytes can be 'browned', i.e., recruited to a more brown-like adipocyte, capable of thermogenesis through increased expression of uncoupling protein 1. The list of browning agents that induce these so-called beige adipocytes is growing constantly. However, the underlying mechanisms are often poorly understood, with the possibility that some of these agents cause browning as a secondary effect. Moreover, it remains unclear whether beige adipocytes can contribute sufficiently to affect whole-body energy expenditure in a functionally significant manner. This review presents an overview of the different molecular pathways leading to the induction of beige fat, including direct stimulation and indirect actions on the CNS or the immune system. We discuss the available evidence on the capacity of beige adipocytes to influence whole-body energy expenditure in rodents, and lastly outline the potential problems of translating browning capacity into the potential treatment of human metabolic diseases. PMID:26450134

  18. 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...

  19. Fat tissue staining and photodynamic/photothermal effects

    Science.gov (United States)

    Tuchin, Valery V.; Altshuler, Gregory B.; Yanina, Irina Yu.; Kochubey, Vyacheslav I.; Simonenko, Georgy V.

    2010-02-01

    Cellulite is considered as a disease of the subcutaneous fat layer that appears mostly in women and consists of changes in fat cell accumulation together with disturbed lymphatic drainage, affecting the external appearance of the skin. The photodynamic and selective photothermal treatments may provide reduction the volume of regional or sitespecific accumulations of subcutaneous adipose tissue on the cellular level. We hypothesize that light irradiation of stained fat tissue at selected temperature leads to fat cell lypolytic activity (the enhancement of lipolysis of cell triglycerides due to expression of lipase activity and cell release of free fat acids (FFAs) due to temporal cell membrane porosity), and cell killing due to apoptosis caused by the induced fat cell stress and/or limited cell necrosis.

  20. Adipose cell hypertrophy precedes the appearance of small adipocytes by 3 days in C57BL/6 mouse upon changing to a high fat diet.

    Science.gov (United States)

    Li, Yanjun; Periwal, Vipul; Cushman, Samuel W; Stenkula, Karin G

    2016-01-01

    Adipose tissue is the energy buffer in mammals. The cellularity of adipose tissue has a major role in determining the response of adipose tissue to insulin action. A reduction in the ability of adipose tissue to store ingested caloric excess can lead to dyslipidemia and lipotoxicity, impacting insulin action systemically. The dynamic response of adipose tissue to changes in diet is therefore a crucial aspect of metabolism, and has attracted attention in the context of the ongoing worldwide increase in overweight and obesity and resulting metabolic syndrome dysfunctions. We investigated in a mouse model if there is a specific delay between an increase in caloric intake and the recruitment of new adipocytes, and if there are other changes in adipose tissue dynamics concomitant with such a diet change. By developing a dynamic mathematical model, we found that there is a delay of 3 days between the start of a high fat diet and the recruitment of new adipocytes, and that the rate of fat mass increase modulates lipid turnover and adipose cell hypertrophy. PMID:27144099

  1. 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

  2. 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.

  3. Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation

    International Nuclear Information System (INIS)

    Incubation of intact rat fat cells with maximally effective concentrations of insulin (1 nM, 12 min) or isoprenaline (300 nM, 3 min) increased particulate cGMP- and cilostamide-inhibited, low-Km cAMP phosphodiesterase (cAMP-PDE) activity by about 50% and 100%, respectively. In 32P-labeled cells, these agents induced serine 32P-phosphorylation of a 135-kDa particulate protein and, to a variable and lesser extent, a 44-kDa protein, which were selectively immunoprecipitated by anti-cAMP-PDE, as analyzed by SDS/PAGE and autoradiography. In the absence of hormonal stimulation, little phosphorylation was detected (less than 10% of that with the hormones). The two phosphoproteins were identified as cAMP-PDE or a closely related molecule (in the case of the 44-kDa species, perhaps a proteolytic fragment) since (i) amounts of 32P in the immunoprecipitated 135-kDa protein paralleled enzyme inactivation, (ii) prior incubation of the anti-cAMP-PDE with the pure rat or bovine enzyme selectively blocked the immunoprecipitation of the phosphoproteins, (iii) 135- and 44-kDa proteins reacted with the anti-cAMP-PDE on Western immunoblots, and (iv) the two phosphoproteins copurified with cAMP-PDE activity through DEAE-Sephacel chromatography and were isolated by highly selective affinity chromatography on cilostamide-agarose. Thus, in fat cells, catecholamine- and insulin-induced activation of the cAMP-PDE may be mediated via phosphorylation by cAMP-dependent protein kinase and an insulin-activated serine protein kinase, respectively

  4. Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation.

    Directory of Open Access Journals (Sweden)

    Kevin J Dudley

    Full Text Available The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2 and 27 (P27 from male offspring of control and MHF mothers (n = 8 per group. Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver∶brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction.

  5. 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.

  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. 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.

  8. 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

  9. 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

  10. 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.

  11. An autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

    International Nuclear Information System (INIS)

    The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status. (author)

  12. Apelin Enhances Brown Adipogenesis and Browning of White Adipocytes.

    Science.gov (United States)

    Than, Aung; He, Hui Ling; Chua, Si Hui; Xu, Dan; Sun, Lei; Leow, Melvin Khee-Shing; Chen, Peng

    2015-06-01

    Brown adipose tissue expends energy in the form of heat via the mitochondrial uncoupling protein UCP1. Recent studies showed that brown adipose tissue is present in adult humans and may be exploited for its anti-obesity and anti-diabetes actions. Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism. Here, we report that apelin-APJ signaling promotes brown adipocyte differentiation by increasing the expressions of brown adipogenic and thermogenic transcriptional factors via the PI3K/Akt and AMPK signaling pathways. It is also found that apelin relieves the TNFα inhibition on brown adipogenesis. In addition, apelin increases the basal activity of brown adipocytes, as evidenced by the increased PGC1α and UCP1 expressions, mitochondrial biogenesis, and oxygen consumption. Finally, we provide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristics in white adipocytes. This study, for the first time, reveals the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to combat obesity and related metabolic disorders. PMID:25931124

  13. Effects of fat preparation methods on the viabilities of autologous fat grafts.

    Science.gov (United States)

    Minn, Kyung-Won; Min, Kyung-Hee; Chang, Hak; Kim, Sukwha; Heo, Eun-Ju

    2010-10-01

    Fat grafts are commonly used in plastic surgery, but their unpredictable absorption rates are a considerable disadvantage. Furthermore, no agreement has been reached regarding the method that best enables fat graft survival. This study aimed to evaluate the effects of different preparation methods on fat graft viability. Fat tissue was harvested from the remnants of transverse rectus abdominis musculocutaneous (TRAM) flaps by syringe aspiration. Harvested fat tissue was prepared using three different methods: centrifugation, metal sieve concentration, and cotton gauze concentration. To evaluate the viabilities of fat cells, XTT assays were performed. For the study, 18 nude mice were allocated to three groups: the centrifugation, metal sieve, and cotton gauze groups (6 mice per group). Prepared fat (1 ml) was injected into the nuchal area of the mice, and 12 weeks later, grafts were dissected to determine graft survival rates and subjected to histologic analysis. No significant differences were observed in graft survival rates and histologic findings (necrosis and vascularity) between the three groups. However, histologic analysis found the metal sieve group to have significantly lower fat cell viability and more inflammation than the other two groups. The findings suggest that the closed centrifugation technique has no advantage over the open cotton gauze technique in terms of fat graft viability, and that the metal sieve concentration method is deficient as a preparation method because it can cause grafted fat degradation. PMID:20442997

  14. 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 ...

  15. 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 ...

  16. Aqueous Extracts of the Marine Brown Alga Lobophora variegata Inhibit HIV-1 Infection at the Level of Virus Entry into Cells

    OpenAIRE

    Kremb, Stephan; Helfer, Markus; Kraus, Birgit; Wolff, Horst; Wild, Christian; Schneider, Martha; Voolstra, Christian R; Brack-Werner, Ruth

    2014-01-01

    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,...

  17. Rhein Protects against Obesity and Related Metabolic Disorders through Liver X Receptor-Mediated Uncoupling Protein 1 Upregulation in Brown Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Xiaoyan Sheng, Xuehua Zhu, Yuebo Zhang, Guoliang Cui, Linling Peng, Xiong Lu, Ying Qin Zang

    2012-01-01

    Full Text Available Liver X receptors (LXRs play important roles in regulating cholesterol homeostasis, and lipid and energy metabolism. Therefore, LXR ligands could be used for the management of metabolic disorders. We evaluated rhein, a natural compound from Rheum palmatum L., as an antagonist for LXRs and investigated its anti-obesity mechanism in high-fat diet-fed mice. Surface plasmon resonance assays were performed to examine the direct binding of rhein to LXRs. LXR target gene expression was assessed in 3T3-L1 adipocytes and HepG2 hepatic cells in vitro. C57BL/6J mice fed a high-fat diet were orally administered with rhein for 4 weeks, and then the expression levels of LXR-related genes were analyzed. Rhein bound directly to LXRs. The expression levels of LXR target genes were suppressed by rhein in 3T3-L1 and HepG2 cells. In white adipose tissue, muscle and liver, rhein reprogrammed the expression of LXR target genes related to adipogenesis and cholesterol metabolism. Rhein activated uncoupling protein 1 (UCP1 expression in brown adipose tissue (BAT in wild-type mice, but did not affect UCP1 expression in LXR knockout mice. In HIB-1B brown adipocytes, rhein activated the UCP1 gene by antagonizing the repressive effect of LXR on UCP1 expression. This study suggests that rhein may protect against obesity and related metabolic disorders through LXR antagonism and regulation of UCP1 expression in BAT.

  18. 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

  19. 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

  20. 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)

  1. Weighing in on Dietary Fats

    Science.gov (United States)

    ... wrong” kinds of fats can trigger additional health hazards. “Some fats are better for our bodies than ... ingredients. “Low-fat and fat-free yogurt and milk still contain the important proteins and minerals found ...

  2. 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...

  3. Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression

    Directory of Open Access Journals (Sweden)

    Yi-Jen Chen

    2011-11-01

    Full Text Available Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs, may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity.

  4. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells.

    Science.gov (United States)

    Hwang, Yong Pil; Choi, Jae Ho; Kim, Hyung Gyun; Khanal, Tilak; Song, Gye Young; Nam, Myoung Soo; Lee, Hyun-Sun; Chung, Young Chul; Lee, Young Chun; Jeong, Hye Gwang

    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. PMID:23319015

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines

    OpenAIRE

    Miller, Aine; Stanton, Catherine; Murphy, John; Devery, Rosaleen

    2003-01-01

    Milk enriched in conjugated linoleic acid (CLA) was obtained from cows on pasture supplemented with full-fat rapeseeds (FFR; 2·26g cis 9, trans 11 (c9, t11)-CLA/100g fatty acid methyl esters) and full-fat soyabeans (1·83g c9, t11-CLA/100g fatty acid methyl esters). A control milk fat (1·69g c9, t11-CLA/100g fatty acid methyl esters) was obtained from cows fed on pasture only. The present study assessed the potency of the CLA-enriched milk fats to modulate biomarkers that had previously been o...

  11. Tune Your Brown Clustering, Please

    DEFF Research Database (Denmark)

    Derczynski, Leon; Chester, Sean; Bøgh, Kenneth Sejdenfaden

    2015-01-01

    Brown clustering, an unsupervised hierarchical clustering technique based on ngram mutual information, has proven useful in many NLP applications. However, most uses of Brown clustering employ the same default configuration; the appropriateness of this configuration has gone predominantly...... 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...... explore the dynamic between the input corpus size, chosen number of classes, and quality of the resulting clusters, which has an impact for any approach using Brown clustering. In every scenario that we examine, our results reveal that the values most commonly used for the clustering are sub-optimal....

  12. Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Shin

    Full Text Available Recent evidence has suggested that AHNAK expression is altered in obesity, although its role in adipose tissue development remains unclear. The objective of this study was to determine the molecular mechanism by which Ahnak influences adipogenesis and glucose homeostasis.We investigated the in vitro role of AHNAK in adipogenesis using adipose-derived mesenchymal stem cells (ADSCs and C3H10T1/2 cells. AHNAK-KO male mice were fed a high-fat diet (HFD; 60% calories from fat and examined for glucose and insulin tolerances, for body fat compositions, and by hyperinsulinemic-euglycemic clamping. Energy expenditures were assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in white or brown adipose tissues.Adipogenesis in ADSCs was impaired in AHNAK-KO mice. The loss of AHNAK led to decreased BMP4/SMAD1 signaling, resulting in the downregulation of key regulators of adipocyte differentiation (P<0.05. AHNAK directly interacted with SMAD1 on the Pparγ2 promoter. Concomitantly, HFD-fed AHNAK-KO mice displayed reduced hepatosteatosis and improved metabolic profiles, including improved glucose tolerance (P<0.001, enhanced insulin sensitivity (P<0.001, and increased energy expenditure (P<0.05, without undergoing alterations in food intake and physical activity.AHNAK plays a crucial role in body fat accumulation by regulating adipose tissue development via interaction with the SMAD1 protein and can be involved in metabolic homeostasis.

  13. 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.

  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. 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.

  17. 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...

  18. 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

  19. (Val(8))GLP-1-Glu-PAL: a GLP-1 agonist that improves hippocampal neurogenesis, glucose homeostasis, and β-cell function in high-fat-fed mice.

    Science.gov (United States)

    Lennox, Rachael; Porter, David W; Flatt, Peter R; Gault, Victor A

    2013-04-01

    This study examined the biological properties of a novel GLP-1 peptide, (Val(8))GLP-1-Glu-PAL, engineered with an Ala(8)→Val(8) substitution and additional incorporation of a C(16) fatty acid moiety at Lys(26) via a glutamic acid linker. GLP-1 underwent 75 % degradation by DPP-IV over 8 h, whereas (Val(8))GLP-1 and (Val(8))GLP-1-Glu-PAL remained intact. All GLP-1 peptides significantly stimulated insulin secretion at 5.6 mM (1.3- to 4.9-fold, peffect on bodyweight or food intake, but significantly lowered non-fasting plasma glucose (43-46 % decrease, pconsumption, CO(2) production, RER, and energy expenditure were not altered by (Val(8))GLP-1-Glu-PAL therapy. Treatment with (Val(8))GLP-1-Glu-PAL resulted in a significant increase in BrdU-positive cells (1.3-fold, p<0.05) in the granule cell layer of the dentate gyrus. These data demonstrate that (Val(8))GLP-1-Glu-PAL is a long-acting GLP-1 peptide that significantly improves hippocampal neurogenesis, glucose homeostasis, and insulin secretion in high-fat-fed mice. PMID:23138973

  20. 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

  1. 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

  2. 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.

  3. 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)

  4. 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

  5. Metabolic interplay between white, beige, brown adipocytes and the liver.

    Science.gov (United States)

    Scheja, Ludger; Heeren, Joerg

    2016-05-01

    In mammalian evolution, three types of adipocytes have developed, white, brown and beige adipocytes. White adipocytes are the major constituents of white adipose tissue (WAT), the predominant store for energy-dense triglycerides in the body that are released as fatty acids during catabolic conditions. The less abundant brown adipocytes, the defining parenchymal cells of brown adipose tissue (BAT), internalize triglycerides that are stored intracellularly in multilocular lipid droplets. Beige adipocytes (also known as brite or inducible brown adipocytes) are functionally very similar to brown adipocytes and emerge in specific WAT depots in response to various stimuli including sustained cold exposure. The activation of brown and beige adipocytes (together referred to as thermogenic adipocytes) causes both the hydrolysis of stored triglycerides as well as the uptake of lipids and glucose from the circulation. Together, these fuels are combusted for heat production to maintain body temperature in mammals including adult humans. Given that heating by brown and beige adipocytes is a very-well controlled and energy-demanding process which entails pronounced shifts in energy fluxes, it is not surprising that an intensive interplay exists between the various adipocyte types and parenchymal liver cells, and that this influences systemic metabolic fluxes and endocrine networks. In this review we will emphasize the role of hepatic factors that regulate the metabolic activity of white and thermogenic adipocytes. In addition, we will discuss the relevance of lipids and hormones that are secreted by white, brown and beige adipocytes regulating liver metabolism in order to maintain systemic energy metabolism in health and disease. PMID:26829204

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.

    Science.gov (United States)

    Galet, Colette; Gollapudi, Kiran; Stepanian, Sevan; Byrd, Joshua B; Henning, Susanne M; Grogan, Tristan; Elashoff, David; Heber, David; Said, Jonathan; Cohen, Pinchas; Aronson, William J

    2014-01-01

    We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell-cycle progression (CCP) score were investigated. Serum fatty acids and eicosanoids were measured by gas chromatography and ELISA. CCP score was determined by quantitative real-time reverse transcriptase PCR (RT-PCR). Associations between serum eicosanoids, Ki67, and CCP score were evaluated using partial correlation analyses. BLT1 (LTB4 receptor) expression was determined in prostate cancer cell lines and prostatectomy specimens. Serum omega-6 fatty acids and 15(S)-HETE levels were significantly reduced, and serum omega-3 levels were increased in the LFFO group relative to the Western diet group, whereas there was no change in LTB4 levels. The CCP score was significantly lower in the LFFO compared with the Western diet group. The 15(S)-HETE change correlated with tissue Ki67 (R = 0.48; P < 0.01) but not with CCP score. The LTB4 change correlated with the CCP score (r = 0.4; P = 0.02) but not with Ki67. The LTB4 receptor BLT1 was detected in prostate cancer cell lines and human prostate cancer specimens. In conclusion, an LFFO diet resulted in decreased 15(S)-HETE levels and lower CCP score relative to a Western diet. Further studies are warranted to determine whether the LFFO diet antiproliferative effects are mediated through the LTB4/BLT1 and 15(S)-HETE pathways. PMID:24169960

  15. 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...

  16. 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.

  17. Generation of Lymph Node-fat Pad Chimeras for the Study of Lymph Node Stromal Cell Origin

    OpenAIRE

    Benezech, Cecile; Caamano, Jorge H

    2013-01-01

    The stroma is a key component of the lymph node structure and function. However, little is known about its origin, exact cellular composition and the mechanisms governing its formation. Lymph nodes are always encapsulated in adipose tissue and we recently demonstrated the importance of this relation for the formation of lymph node stroma. Adipocyte precursor cells migrate into the lymph node during its development and upon engagement of the Lymphotoxin-b receptor switch off adipogenesis and d...

  18. Cytoplasmic inheritance of organelles in brown algae.

    Science.gov (United States)

    Motomura, Taizo; Nagasato, Chikako; Kimura, Kei

    2010-03-01

    Brown algae, together with diatoms and chrysophytes, are a member of the heterokonts. They have either a characteristic life cycle of diplohaplontic alternation of gametophytic and sporophytic generations that are isomorphic or heteromorphic, or a diplontic life cycle. Isogamy, anisogamy and oogamy have been recognized as the mode of sexual reproduction. Brown algae are the characteristic group having elaborated multicellular organization within the heterokonts. In this study, cytoplasmic inheritance of chloroplasts, mitochondria and centrioles was examined, with special focus on sexual reproduction and subsequent zygote development. In oogamy, chloroplasts and mitochondria are inherited maternally. In isogamy, chloroplasts in sporophyte cells are inherited biparentally (maternal or paternal); however, mitochondria (or mitochondrial DNA) derived from the female gamete only remained during zygote development after fertilization. Centrioles in zygotes are definitely derived from the male gamete, irrespective of the sexual reproduction pattern. Female centrioles in zygotes are selectively broken down within 1-2 h after fertilization. The remaining male centrioles play a crucial role as a part of the centrosome for microtubule organization, mitosis, determination of the cytokinetic plane and cytokinesis, as well as for maintaining multicellularity and regular morphogenesis in brown algae. PMID:20145971

  19. 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.

  20. 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. PMID:27230905

  1. 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.

  2. 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

  3. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity

    OpenAIRE

    Chao, Pei-Ting; Liang YANG; Aja, Susan; Moran, Timothy H.; Bi, Sheng

    2011-01-01

    Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympa...

  4. Brown coal and the climate

    International Nuclear Information System (INIS)

    The undisputed aims of a sensible energy policy are safety, reasonable prices, environmental compatibility and saving resources. Each energy source and every form of energy conversion and use has specific advantages and disadvantages which must be weighed up. It is in favour of brown coal that it can succeed in international competition and therefore offers security of supply, economy, productivity and employment. The mining and use of brown coal comply with the highest environmental standards, in international comparison. Against this, mining brown coal by strip mining inevitably involves intervention in the environment and the social structure of the coalfield. Burning brown coal to generate electricity in powerstations is specifically connected with high CO2 emission. (orig.)

  5. Facts about polyunsaturated fats

    Science.gov (United States)

    ... with higher amounts of polyunsaturated fats include: Walnuts Sunflower seeds Flax seeds or flax oil Fish, such as salmon, mackerel, herring, albacore tuna, and trout Corn oil Soybean oil Safflower oil To get the health benefits, you need to replace unhealthy fats with healthy ...

  6. 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

  7. 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 ...

  8. Glycerol-3-phosphate Acyltransferase Isoform-4 (GPAT4) Limits Oxidation of Exogenous Fatty Acids in Brown Adipocytes

    DEFF Research Database (Denmark)

    Cooper, Daniel E; Grevengoed, Trisha J; Klett, Eric L; Coleman, Rosalind A

    2015-01-01

    loss, because both cold tolerance and response to a β3-adrenergic agonist were similar in both genotypes. Because GPAT4 comprises 65% of the total GPAT activity in brown adipose tissue (BAT), we characterized BAT function. A 45% fat diet increased the Gpat4(-/-) BAT expression of peroxisome......Glycerol-3-phosphate acyltransferase-4 (GPAT4) null pups grew poorly during the suckling period and, as adults, were protected from high fat diet-induced obesity. To determine why Gpat4(-/-) mice failed to gain weight during these two periods of high fat feeding, we examined energy metabolism....... Compared with controls, the metabolic rate of Gpat4(-/-) mice fed a 45% fat diet was 12% higher. Core body temperature was 1 ºC higher after high fat feeding. Food intake, fat absorption, and activity were similar in both genotypes. Impaired weight gain in Gpat4(-/-) mice did not result from increased heat...

  9. A Conversation with Larry Brown

    OpenAIRE

    Dasgupta, Anirban

    2005-01-01

    Lawrence D. Brown was born on December 16, 1940 in Los Angeles, California. He obtained his Ph.D. in mathematics from Cornell University in 1964. He has been on the faculty of the University of California, Berkeley, Cornell University, Rutgers University and, most recently, the Wharton School of the University of Pennsylvania, where he holds the Miers Busch Professorship of Statistics. Professor Brown was President of the Institute of Mathematical Statistics in 1992–1993, Coeditor of The Anna...

  10. 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

  11. 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.

  12. 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.

  13. Brown tumor mimicking maxillary sinus mucocele as the first manifestation of primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Guldfred, Liviu-Adelin; Daugaard, Søren; von Buchwald, Christian

    2012-01-01

    We describe the first case of brown tumor mimicking a maxillary sinus mucocele as the first manifestation of the patient's primary hyperparathyroidism. A 34-year old woman presented with a 14 days history of elevation of the right orbit, retrobulbar pain and cheek anesthesia. The CT and MR...... either giant cell granuloma or brown tumor. The finding of hyperparathyroidism confirmed the diagnosis of brown tumor. To our knowledge, this is the first report of cystic brown tumor mimicking a mucocele of the maxillary sinus....

  14. 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

  15. Tuberose sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma

    Energy Technology Data Exchange (ETDEWEB)

    Patel, U. [Department of Radiology, St George' s Hospital, London (United Kingdom)]. E-mail: uday.patel@stgeorges.nhs.uk; Simpson, E. [Department of Radiology, St George' s Hospital, London (United Kingdom); Kingswood, J.C. [Department of Clinical Genetics, St George' s Hospital, London (United Kingdom); Saggar-Malik, A.K. [Department of Clinical Genetics, St George' s Hospital, London (United Kingdom)

    2005-06-01

    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.

  16. 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

  17. 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

  18. 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

    OpenAIRE

    Dmitry Bulgin; Erik Vrabic; Enes Hodzic

    2013-01-01

    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 o...

  19. Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity.

    OpenAIRE

    Derecka, Marta; Gornicka, Agnieszka; Koralov, Sergei B.; Szczepanek, Karol; Morgan, Magdalena; Raje, Vidisha; Sisler, Jennifer; Zhang, Qifang; Otero, Dennis; Cichy, Joanna; Rajewsky, Klaus; Shimoda, Kazuya; Poli, Valeria; Strobl, Birgit; Pellegrini, Sandra

    2012-01-01

    Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2−/− brown preadipocytes. Furthermore, Tyk2−/− mice express...

  20. 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...