Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

NARCIS (Netherlands)

A. Grefhorst (Aldo); J.C. van den Beukel (Anneke); 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

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

DEFF Research Database (Denmark)

Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

2015-01-01

. Conclusions: Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides...... NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time...

A low-protein, high-carbohydrate diet increases browning in perirenal adipose tissue but not in inguinal adipose tissue.

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Pereira, Mayara P; Ferreira, Laís A A; da Silva, Flávia H S; Christoffolete, Marcelo A; Metsios, George S; Chaves, Valéria E; de França, Suélem A; Damazo, Amílcar S; Flouris, Andreas D; Kawashita, Nair H

2017-10-01

The aim of this study was to evaluate the browning and origin of fatty acids (FAs) in the maintenance of triacylglycerol (TG) storage and/or as fuel for thermogenesis in perirenal adipose tissue (periWAT) and inguinal adipose tissue (ingWAT) of rats fed a low-protein, high-carbohydrate (LPHC) diet. LPHC (6% protein, 74% carbohydrate) or control (C; 17% protein, 63% carbohydrate) diets were administered to rats for 15 d. The tissues were stained with hematoxylin and eosin for histologic analysis. The content of uncoupling protein 1 (UCP1) was determined by immunofluorescence. Levels of T-box transcription factor (TBX1), PR domain containing 16 (PRDM16), adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase, lipoprotein lipase (LPL), glycerokinase, phosphoenolpyruvate carboxykinase (PEPCK), glucose transporter 4, β 3 -adrenergic receptor (AR), β 1 -AR, protein kinase A (PKA), adenosine-monophosphate-activated protein kinase (AMPK), and phospho-AMPK were determined by immunoblotting. Serum fibroblast growth factor 21 (FGF21) was measured using a commercial kit (Student's t tests, P diet increased FGF21 levels by 150-fold. The presence of multilocular adipocytes, combined with the increased contents of UCP1, TBX1, and PRDM16 in periWAT of LPHC-fed rats, suggested the occurrence of browning. The contents of β 1 -AR and LPL were increased in the periWAT. The ingWAT showed higher ATGL and PEPCK levels, phospho-AMPK/AMPK ratio, and reduced β 3 -AR and PKA levels. These findings suggest that browning occurred only in the periWAT and that higher utilization of FAs from blood lipoproteins acted as fuel for thermogenesis. Increased glycerol 3-phosphate generation by glyceroneogenesis increased FAs reesterification from lipolysis, explaining the increased TG storage in the ingWAT. Copyright © 2017 Elsevier Inc. All rights reserved.

MRI characterization of brown adipose tissue in obese and normal-weight children

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Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Zhang, Huiyuan [John H. Stroger, Jr. Hospital of Cook County, Collaborative Research Unit, Chicago, IL (United States); Kwon, Soyang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Stanley Manne Children' s Research Institute, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Josefson, Jami L. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Endocrinology, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States)

2015-10-15

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

MRI characterization of brown adipose tissue in obese and normal-weight children

International Nuclear Information System (INIS)

Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M.; Schoeneman, Samantha E.; Zhang, Huiyuan; Kwon, Soyang; Josefson, Jami L.

2015-01-01

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

Brown Adipose Tissue Bioenergetics: A New Methodological Approach

Science.gov (United States)

Calderon‐Dominguez, María; Alcalá, Martín; Sebastián, David; Zorzano, Antonio; Viana, Marta; Serra, Dolors

2017-01-01

The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT. Based on XF Seahorse Technology, we assessed the appropriate weight of the explants, the exact concentration of each inhibitor in the reaction, and the specific incubation time to optimize bioenergetics measurements. Our results show that BAT basal oxygen consumption is mostly due to proton leak. In addition, BAT presents higher basal oxygen consumption than white adipose tissue and a positive response to b‐adrenergic stimulation. Considering the whole tissue and not just subcellular populations is a direct approach that provides a realistic view of physiological respiration. In addition, it can be adapted to analyze the effect of potential activators of thermogenesis, or to assess the use of fatty acids or glucose as a source of energy. PMID:28435771

Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues

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Harkema Jack R

2011-07-01

Full Text Available Abstract Background Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model. Methods Male ApoE knockout (ApoE-/- mice inhaled concentrated fine ambient PM (PM 2.5 or filtered air (FA for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM2.5 exposure in different adipose depots of ApoE-/- mice to understand responses to chronic inhalational stimuli. Results Exposure to PM2.5 induced an increase in the production of reactive oxygen species (ROS in brown adipose depots. Additionally, exposure to PM2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT and brown adipose tissues (BAT, while mitochondrial size was also reduced in BAT. In BAT, PM2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated. Conclusions PM2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.

Two key temporally distinguishable molecular and cellular components of white adipose tissue browning during cold acclimation.

Science.gov (United States)

Jankovic, Aleksandra; Golic, Igor; Markelic, Milica; Stancic, Ana; Otasevic, Vesna; Buzadzic, Biljana; Korac, Aleksandra; Korac, Bato

2015-08-01

White to brown adipose tissue conversion and thermogenesis can be ignited by different conditions or agents and its sustainability over the long term is still unclear. Browning of rat retroperitoneal white adipose tissue (rpWAT) during cold acclimation involves two temporally apparent components: (1) a predominant non-selective browning of most adipocytes and an initial sharp but transient induction of uncoupling protein 1, peroxisome proliferator-activated receptor (PPAR) coactivator-1α, PPARγ and PPARα expression, and (2) the subsistence of relatively few thermogenically competent adipocytes after 45 days of cold acclimation. The different behaviours of two rpWAT beige/brown adipocyte subsets control temporal aspects of the browning process, and thus regulation of both components may influence body weight and the potential successfulness of anti-obesity therapies. Conversion of white into brown adipose tissue may have important implications in obesity resistance and treatment. Several browning agents or conditions ignite thermogenesis in white adipose tissue (WAT). To reveal the capacity of WAT to function in a brownish/burning mode over the long term, we investigated the progression of the rat retroperitoneal WAT (rpWAT) browning during 45 days of cold acclimation. During the early stages of cold acclimation, the majority of rpWAT adipocytes underwent multilocularization and thermogenic-profile induction, as demonstrated by the presence of a multitude of uncoupling protein 1 (UCP1)-immunopositive paucilocular adipocytes containing peroxisome proliferator-activated receptor (PPAR) coactivator-1α (PGC-1α) and PR domain-containing 16 (PRDM16) in their nuclei. After 45 days, all adipocytes remained PRDM16 immunopositive, but only a few multilocular adipocytes rich in mitochondria remained UCP1/PGC-1α immunopositive. Molecular evidence showed that thermogenic recruitment of rpWAT occurred following cold exposure, but returned to starting levels after cold

Metabolic characteristics and therapeutic potential of brown and ?beige? adipose tissues

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Ekaterina Olegovna Koksharova

2014-10-01

Full Text Available According to the International Diabetes Federation, 10.9 million people have diabetes mellitus (DM in Russia; however, only up to 4 million are registered. In addition, 11.9 million people have impaired glucose tolerance and impaired fasting glucose levels [1]. One of the significant risk factors for type 2 DM (T2DM is obesity, which increases insulin resistance (IR. IR is the major pathogenetic link to T2DM. According to current concepts, there are three types of adipose tissue: white adipose tissue (WAT, brown adipose tissue (BAT and ?beige?, of which the last two types have a thermogenic function. Some research results have revealed the main stages in the development of adipocytes; however, there is no general consensus regarding the development of ?beige? adipocytes. Furthermore, the biology of BAT and ?beige? adipose tissue is currently being intensively investigated, and some key transcription factors, signalling pathways and hormones that promote the development and activation of these tissues have been identified. The most discussed hormones are irisin and fibroblast growth factor 21, which have established positive effects on BAT and ?beige? adipose tissue with regard to carbohydrate, lipid and energy metabolism. The primary imaging techniques used to investigate BAT are PET-CT with 18F-fluorodeoxyglucose and magnetic resonance spectroscopy. With respect to the current obesity epidemic and associated diseases, including T2DM, there is a growing interest in investigating adipogenesis and the possibility of altering this process. BAT and ?beige? adipose tissue may be targets for developing drugs directed against obesity and T2DM.

Identification and characterization of a supraclavicular brown adipose tissue in mice

Science.gov (United States)

A fundamental challenge to our understanding of brown adipose tissue (BAT) is the lack of an animal model that faithfully represents human BAT. Such a model is essential for direct assessment of the function and therapeutic potential of BAT depots in humans. In human adults, most of the thermoactive...

Functionally enhanced brown adipose tissue in Ames dwarf mice.

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Darcy, Justin; Bartke, Andrzej

2017-01-02

Reduced insulin-like growth factor 1/insulin signaling (IIS) has been linked to extended longevity in species ranging from yeast to mammals. In mammals, this is exemplified in Ames dwarf (Prop1 df/df ) mice, which have a 40%-60% increase in longevity (males and females, respectively) due to their recessive Prop1 loss-of-function mutation that results in lack of growth hormone (GH), thyroid-stimulating hormone and prolactin. Our laboratory has previously shown that Ames dwarf mice have functionally unique white adipose tissue (WAT) that improves, rather than impairs, insulin sensitivity. Because GH and thyroid hormone are integral to adipose tissue development and function, we hypothesized that brown adipose tissue (BAT) in Ames dwarf mice may also be functionally unique and/or enhanced. Here, we elaborate on our recent findings, which demonstrate that BAT is functionally enhanced in Ames dwarf mice, and suggest that BAT removal in these mice results in utilization of WAT depots as an energy source. We also discuss how our findings compare to those in other long-lived dwarf mice with altered IIS, which unlike Ames dwarf mice, are essentially euthyroid. Lastly, we provide some insights into the implications of these findings and discuss some of the necessary future work in this area.

UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity

DEFF Research Database (Denmark)

Madsen, Lise; Pedersen, Lone M; Lillefosse, Haldis Haukaas

2010-01-01

attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality. CONCLUSIONS/SIGNIFICANCE: Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose...... tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity...

Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans

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Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. T...

Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing.

Science.gov (United States)

Gonzalez-Hurtado, Elsie; Lee, Jieun; Choi, Joseph; Wolfgang, Michael J

2018-01-01

To determine the role of fatty acid oxidation on the cellular, molecular, and physiologic response of brown adipose tissue to disparate paradigms of chronic thermogenic stimulation. Mice with an adipose-specific loss of Carnitine Palmitoyltransferase 2 (Cpt2 A-/- ), that lack mitochondrial long chain fatty acid β-oxidation, were subjected to environmental and pharmacologic interventions known to promote thermogenic programming in adipose tissue. Chronic administration of β3-adrenergic (CL-316243) or thyroid hormone (GC-1) agonists induced a loss of BAT morphology and UCP1 expression in Cpt2 A-/- mice. Fatty acid oxidation was also required for the browning of white adipose tissue (WAT) and the induction of UCP1 in WAT. In contrast, chronic cold (15 °C) stimulation induced UCP1 and thermogenic programming in both control and Cpt2 A-/- adipose tissue albeit to a lesser extent in Cpt2 A-/- mice. However, thermoneutral housing also induced the loss of UCP1 and BAT morphology in Cpt2 A-/- mice. Therefore, adipose fatty acid oxidation is required for both the acute agonist-induced activation of BAT and the maintenance of quiescent BAT. Consistent with this data, Cpt2 A-/- BAT exhibited increased macrophage infiltration, inflammation and fibrosis irrespective of BAT activation. Finally, obese Cpt2 A-/- mice housed at thermoneutrality exhibited a loss of interscapular BAT and were refractory to β3-adrenergic-induced energy expenditure and weight loss. Mitochondrial long chain fatty acid β-oxidation is critical for the maintenance of the brown adipocyte phenotype both during times of activation and quiescence. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

OpenAIRE

Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone–fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues – subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT – is differently associated wi...

The role of active brown adipose tissue in human metabolism

Energy Technology Data Exchange (ETDEWEB)

Ozguven, Salih; Turoglu, H.T. [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Ones, Tunc [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Kozyatagi/Kadikoy, Istanbul (Turkey); Yilmaz, Yusuf; Imeryuz, Nese [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Internal Medicine, Division of Gastroenterology, Istanbul (Turkey)

2016-02-15

The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing {sup 18}F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the {sup 18}F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females.

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Robinson, Lindsay J; Law, James M; Symonds, Michael E; Budge, Helen

2016-04-01

What is the central question of this study? Does psychological stress, which is known to promote cortisol secretion, simultaneously activate brown adipose tissue function in healthy adult females? What is the main finding and its importance? One explanation for the pronounced differences in brown adipose tissue function between individuals lies in their responsiveness to psychological stress and, as such, should be taken into account when examining its in vivo stimulation. Brown adipose tissue (BAT) has been implicated in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and is a potential therapeutic target. Brown adipose tissue can have a significant impact on energy balance and glucose homeostasis through the action of uncoupling protein 1, dissipating chemical energy as heat following neuroendocrine stimulation. We hypothesized that psychological stress, which is known to promote cortisol secretion, would simultaneously activate BAT at thermoneutrality. Brown adipose tissue activity was measured using infrared thermography to determine changes in the temperature of the skin overlying supraclavicular BAT (TSCR ). A mild psychological stress was induced in five healthy, lean, female, Caucasian volunteers using a short mental arithmetic (MA) test. The TSCR was compared with a repeated assessment, in which the MA test was replaced with a period of relaxation. Although MA did not elicit an acute stress response, anticipation of MA testing led to an increase in salivary cortisol, indicative of an anticipatory stress response, that was associated with a trend towards higher absolute and relative TSCR . A positive correlation between TSCR and cortisol was found during the anticipatory phase, a relationship that was enhanced by increased cortisol linked to MA. Our findings suggest that subtle changes in the level of psychological stress can stimulate BAT, findings that may account for the high variability and inconsistency in reported BAT

A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening

DEFF Research Database (Denmark)

van den Berg, Rosa; Kooijman, Sander; Noordam, Raymond

2018-01-01

-amplitude rhythm in fatty acid uptake by BAT that synchronized with the light/dark cycle. Highest uptake was found at the onset of the active period, which coincided with high lipoprotein lipase expression and low angiopoietin-like 4 expression by BAT. Diurnal rhythmicity in BAT activity determined the rate...... the therapeutic potential of promoting BAT activity. van den Berg et al. show a strong circadian rhythm in fatty acid uptake by brown adipose tissue that peaks at wakening regardless of the light exposure period. Consequently, postprandial lipid handling by brown adipose tissue is highest at wakening, resulting...

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

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Delphine Duteil

2016-10-01

Full Text Available Previous work indicated that lysine-specific demethylase 1 (Lsd1 can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

OpenAIRE

Peixoto, T.C.; Moura, E.G.; Oliveira, E.; Younes-Rapozo, V.; Soares, P.N.; Rodrigues, V.S.T.; Santos, T.R.; Peixoto-Silva, N.; Carvalho, J.C.; Calvino, C.; Conceição, E.P.S.; Guarda, D.S.; Claudio-Neto, S.; Manhães, A.C.; Lisboa, P.C.

2018-01-01

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower ...

The role of adipose tissue in cancer-associated cachexia.

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Vaitkus, Janina A; Celi, Francesco S

2017-03-01

Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment.

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Zhang, Yuqi; Liu, Qiongming; Yu, Jicheng; Yu, Shuangjiang; Wang, Jinqiang; Qiang, Li; Gu, Zhen

2017-09-26

Obesity is one of the most serious public health problems in the 21st century that may lead to many comorbidities such as type-2 diabetes, cardiovascular diseases, and cancer. Current treatments toward obesity including diet, physical exercise, pharmacological therapy, as well as surgeries are always associated with low effectiveness or undesired systematical side effects. In order to enhance treatment efficiency with minimized side effects, we developed a transcutaneous browning agent patch to locally induce adipose tissue transformation. This microneedle-based patch can effectively deliver browning agents to the subcutaneous adipocytes in a sustained manner and switch on the "browning" at the targeted region. It is demonstrated that this patch reduces treated fat pad size, increases whole body energy expenditure, and improves type-2 diabetes in vivo in a diet-induced obesity mouse model.

Pre-medication to block [18F]FDG uptake in the brown adipose tissue of pediatric and adolescent patients

International Nuclear Information System (INIS)

Gelfand, Michael J.; O'Hara, Sara M.; Curtwright, Lois A.; MacLean, Joseph R.

2005-01-01

Radiopharmaceutical uptake of [ 18 F]2-deoxy-2-glucose (FDG) in brown adipose tissue is noted on 15-20% of positron emission tomography (PET) scans in children and adolescents. To determine whether [ 18 F]FDG uptake in brown adipose tissue can be adequately blocked by pre-medication other than moderate-dose oral diazepam. One hundred and eighteen [ 18 F]FDG PET body imaging studies were performed in 69 pediatric patients with a variety of solid tumors. The mean age at the time of imaging was 12.9 years (range 1.2-22.6 years), and 33 studies were performed in patients younger than 10 years old. Seventy-six were performed in boys and 42 in girls. Patients were imaged using a dedicated PET camera. Pre-medication was given in 88 studies: 45 received intravenous fentanyl (0.75-1.0 μg/kg), 34 received low-dose oral diazepam (0.06 mg/kg) and 9 received moderate-dose oral diazepam (0.10 mg/kg). Thirty patients received no pre-medication, 7 of whom were known to have received opiates for pain during the 12 h before the study. Six body regions in the neck and chest were reviewed for [ 18 F]FDG uptake in brown adipose tissue. Uptake of FDG in brown fat was visually graded: 0 for no FDG uptake, 1 for low-grade uptake, 2 for moderate uptake, and 3 for intense uptake. Visual grades 2 and 3 were considered to interfere potentially with image interpretation in the neck and chest. Data were analyzed by multivariate regression using a Poisson distribution. [ 18 F]FDG uptake in brown adipose tissue was most often seen in the lateral neck region and superior and lateral to the lungs (in 36 and 39 studies, respectively). Uptake was also seen near the costovertebral junctions (15 studies), in the superior and central neck in 7 studies and in the anterior mediastinum in 2. Brown adipose tissue uptake was thought to interfere potentially with image interpretation (visual grades 2 and 3) in 19 studies - in 6 of 23 (26.1%) studies after no pre-medication and no opiates for pain, in 10 of

Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

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Gunawardana, Subhadra C.; Piston, David W.

2012-01-01

Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized glucose tolerance, reduced tissue inflammation, and reversal of clinical diabetes markers such as polyuria, polydipsia, and polyphagia. These effects are independent of insulin but correlate with recovery of the animals’ white adipose tissue. BAT transplants lead to significant increases in adiponectin and leptin, but with levels that are static and not responsive to glucose. Pharmacological blockade of the insulin receptor in BAT transplant mice leads to impaired glucose tolerance, similar to what is seen in nondiabetic animals, indicating that insulin receptor activity plays a role in the reversal of diabetes. One possible candidate for activating the insulin receptor is IGF-1, whose levels are also significantly elevated in BAT transplant mice. Thus, we propose that the combined action of multiple adipokines establishes a new equilibrium in the animal that allows for chronic glycemic control without insulin. PMID:22315305

Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning

Science.gov (United States)

Neinast, Michael D.; Frank, Aaron P.; Zechner, Juliet F.; Li, Quanlin; Vishvanath, Lavanya; Palmer, Biff F.; Aguirre, Vincent; Gupta, Rana K.; Clegg, Deborah J.

2015-01-01

Objective Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These ‘BRITE/beige’ adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as “browning.” Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions Upregulation of Nppb, Npr1, Npr2, and β3-adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive

Hot heads & cool bodies: The conundrums of human brown adipose tissue (BAT) activity research

NARCIS (Netherlands)

Bahler, Lonneke; Holleman, Frits; Booij, Jan; Hoekstra, Joost B.; Verberne, Hein J.

2017-01-01

Brown adipose tissue is able to increase energy expenditure by converting glucose and fatty acids into heat. Therefore, BAT is able to increase energy expenditure and could thereby facilitate weight loss or at least weight maintenance. Since cold is a strong activator of BAT, most prospective

Metformin Targets Brown Adipose Tissue in vivo and Reduces Oxygen Consumption in vitro

DEFF Research Database (Denmark)

Breining, Peter; Jensen, Jonas B; Sundelin, Elias I

2018-01-01

basic metabolic rate, making BAT an attractive target for treatment of type 2 diabetes. Under the hypothesis that BAT is a metformin target tissue, we investigated in vivo uptake of [11 C]-metformin tracer in mice and studied in vitro effects of metformin on cultured human brown adipocytes. Injected [11......Metformin is the most widely prescribed oral antidiabetic drug worldwide. Despite well-documented beneficial effects on health outcomes in diabetic patients, the target organs that mediate the effects of metformin remain to be established. In adult humans, brown adipose tissue (BAT) can influence...... uptake. Gene expression profiles of OCTs in BAT revealed ample OCT3 expression in both human and mouse BAT. Incubation of a human brown adipocyte cell models with metformin reduced cellular oxygen consumption in a dose dependent manner. Collectively, these results support BAT as a putative metformin...

Pre-medication to block [{sup 18}F]FDG uptake in the brown adipose tissue of pediatric and adolescent patients

Energy Technology Data Exchange (ETDEWEB)

Gelfand, Michael J.; O' Hara, Sara M.; Curtwright, Lois A.; MacLean, Joseph R. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

2005-10-01

Radiopharmaceutical uptake of [{sup 18}F]2-deoxy-2-glucose (FDG) in brown adipose tissue is noted on 15-20% of positron emission tomography (PET) scans in children and adolescents. To determine whether [{sup 18}F]FDG uptake in brown adipose tissue can be adequately blocked by pre-medication other than moderate-dose oral diazepam. One hundred and eighteen [{sup 18}F]FDG PET body imaging studies were performed in 69 pediatric patients with a variety of solid tumors. The mean age at the time of imaging was 12.9 years (range 1.2-22.6 years), and 33 studies were performed in patients younger than 10 years old. Seventy-six were performed in boys and 42 in girls. Patients were imaged using a dedicated PET camera. Pre-medication was given in 88 studies: 45 received intravenous fentanyl (0.75-1.0 {mu}g/kg), 34 received low-dose oral diazepam (0.06 mg/kg) and 9 received moderate-dose oral diazepam (0.10 mg/kg). Thirty patients received no pre-medication, 7 of whom were known to have received opiates for pain during the 12 h before the study. Six body regions in the neck and chest were reviewed for [{sup 18}F]FDG uptake in brown adipose tissue. Uptake of FDG in brown fat was visually graded: 0 for no FDG uptake, 1 for low-grade uptake, 2 for moderate uptake, and 3 for intense uptake. Visual grades 2 and 3 were considered to interfere potentially with image interpretation in the neck and chest. Data were analyzed by multivariate regression using a Poisson distribution. [{sup 18}F]FDG uptake in brown adipose tissue was most often seen in the lateral neck region and superior and lateral to the lungs (in 36 and 39 studies, respectively). Uptake was also seen near the costovertebral junctions (15 studies), in the superior and central neck in 7 studies and in the anterior mediastinum in 2. Brown adipose tissue uptake was thought to interfere potentially with image interpretation (visual grades 2 and 3) in 19 studies - in 6 of 23 (26.1%) studies after no pre-medication and no

Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue.

Science.gov (United States)

Miao, Yifei; Wu, Wanfu; Dai, Yubing; Maneix, Laure; Huang, Bo; Warner, Margaret; Gustafsson, Jan-Åke

2015-11-10

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

The sexually dimorphic adipose fin is an androgen target tissue in the brown trout (Salmo trutta fario).

Science.gov (United States)

Hisar, Olcay; Sönmez, Adem Yavuz; Hisar, Şükriye Aras; Budak, Harun; Gültepe, Nejdet

2013-04-01

An investigation has been described on the relationship of body length, age and sex with adipose fin length and the number of androgen receptor (AR)-containing cells in the adipose fin as a secondary sexual characteristic for brown trout (Salmo trutta fario). Firstly, body and adipose fin lengths of 2- to 5-year-old brown trout were measured. Thereafter, these fish were killed by decapitation, then their sexes were determined, and adipose fins were excised. The cellular bases of AR binding activities in the adipose fins were analyzed with an antibody against human/rat AR peptide. Immunocytochemistry and western blotting techniques were performed with this antibody. Analysis of morphological measurements indicated that body length and age had a linear relationship with adipose fin length. The coefficients of determination for the body length and age were 0.92 and 0.85 in the male fish and 0.76 and 0.73 in the female fish against the adipose fin length, respectively. At 2 years of age, cells in the adipose fin did not exhibit AR immunoreactivity. However, AR-immunopositive cells were abundant in the adipose fin of 3- to 5-year-old fish. Moreover, the number of AR-immunopositive cells was significantly (P brown trout is a probable target for androgen action and that tissue function or development may to some extent be androgen dependent. In addition, it is likely that such an effect will be mediated by specific androgen receptors.

Brown adipose tissue is linked to a distinct thermoregulatory response to mild cold in people

Science.gov (United States)

Brown adipose tissue (BAT) plays an important role in thermoregulation in rodents. Its role in temperature homeostasis in people is less studied. To this end, we recruited 18 men [8 subjects with no/minimal BAT activity (BAT-) and 10 with pronounced BAT activity (BAT+)]. Each volunteer participated ...

Brown adipose tissue (BAT specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation

Directory of Open Access Journals (Sweden)

Juliane Weiner

2017-06-01

Full Text Available Objective: Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT biology. Methods: We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT and plasma levels. Vaspin expression was analyzed in isolated white and brown adipocytes during adipogenesis and in response to adrenergic stimuli. DNA-methylation within the vaspin promoter was analyzed to investigate acute epigenetic changes after cold-exposure in BAT. Results: Our results demonstrate a strong induction of vaspin mRNA and protein expression specifically in BAT of both cold-exposed and high-fat (HF or high-sugar (HS fed mice. While obesogenic diets also upregulated hepatic vaspin mRNA levels, cold exposure tended to increase vaspin gene expression of inguinal white adipose tissue (iWAT depots. Concomitantly, vaspin plasma levels were decreased upon obesogenic or thermogenic triggers. Vaspin expression was increased during adipogenesis but unaffected by sympathetic activation in brown adipocytes. Analysis of vaspin promoter methylation in AT revealed lowest methylation levels in BAT, which were acutely reduced after cold exposure. Conclusions: Our data demonstrate a novel BAT-specific regulation of vaspin gene expression upon physiological stimuli in vivo with acute epigenetic changes that may contribute to cold-induced expression in BAT. We conclude that these findings indicate functional relevance and potentially beneficial effects of vaspin in BAT function. Keywords: Brown adipose tissue, Browning, Cold exposure, DNA methylation, High-fat diet, High-sucrose diet, SerpinA12, Thermogenesis

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

Energy Technology Data Exchange (ETDEWEB)

Soederlund, Veli [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden)

2007-07-15

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 {beta}-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.)

Mycobacterium canettii Infection of Adipose Tissues.

Science.gov (United States)

Bouzid, Fériel; Brégeon, Fabienne; Poncin, Isabelle; Weber, Pascal; Drancourt, Michel; Canaan, Stéphane

2017-01-01

Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii , a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18-22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii ( p = 0.02) and M. tuberculosis ( p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis ( p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii , it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues.

ROS production in brown adipose tissue mitochondria: The question of UCP1-dependence

Czech Academy of Sciences Publication Activity Database

Shabalina, I.G.; Vrbacký, Marek; Pecinová, Alena; Kalinovich, A. V.; Drahota, Zdeněk; Houštěk, Josef; Mráček, Tomáš; Cannon, B.; Nedergaard, J.

2014-01-01

Roč. 1837, č. 12 (2014), s. 2017-2030 ISSN 0005-2728 R&D Projects: GA MŠk(CZ) LL1204; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : reactive oxygen species * uncoupling protein 1 * brown adipose tissue mitochondria * cold acclimation * glycerol-3-phosphate dehydrogenase (EC 1.1.5.3) * succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.353, year: 2014

Mitochondrial biogenesis in brown adipose tissue is associated with differential expression of transcription regulatory factors

Czech Academy of Sciences Publication Activity Database

Villena, J. A.; Carmona, M. C.; Rodriguez de la Concepción, M.; Rossmeisl, Martin; Vinas, O.; Mampel, T.; Iglesias, R.; Giralt, M.; Villarroya, F.

2002-01-01

Roč. 59, č. 11 (2002), s. 1934-1944 ISSN 1420-682X Grant - others:Ministerio de Ciencia y Tecnología (ES) PM98.0188 Institutional research plan: CEZ:AV0Z5011922 Keywords : brown adipose tissue * mitochondria * transcription factors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.259, year: 2002

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

DEFF Research Database (Denmark)

Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

2015-01-01

abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose...

Foraging at wastewater treatment works affects brown adipose tissue fatty acid profiles in banana bats

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Kate Hill

2016-02-01

Full Text Available In this study we tested the hypothesis that the decrease in habitat quality at wastewater treatment works (WWTW, such as limited prey diversity and exposure to the toxic cocktail of pollutants, affect fatty acid profiles of interscapular brown adipose tissue (iBrAT in bats. Further, the antioxidant capacity of oxidative tissues such as pectoral and cardiac muscle may not be adequate to protect those tissues against reactive molecules resulting from polyunsaturated fatty acid auto-oxidation in the WWTW bats. Bats were sampled at two urban WWTW, and two unpolluted reference sites in KwaZulu-Natal, South Africa. Brown adipose tissue (BrAT mass was lower in WWTW bats than in reference site bats. We found lower levels of saturated phospholipid fatty acids and higher levels of mono- and polyunsaturated fatty acids in WWTW bats than in reference site bats, while C18 desaturation and n-6 to n-3 ratios were higher in the WWTW bats. This was not associated with high lipid peroxidation levels in pectoral and cardiac muscle. Combined, these results indicate that WWTW bats rely on iBrAT as an energy source, and opportunistic foraging on abundant, pollutant-tolerant prey may change fatty acid profiles in their tissue, with possible effects on mitochondrial functioning, torpor and energy usage.

Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue

Czech Academy of Sciences Publication Activity Database

Pravenec, Michal; Mlejnek, Petr; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Šilhavý, Jan; Strnad, Hynek; Eigner, Sebastian; Eigner-Henke, Kateřina; Škop, V.; Malínská, H.; Trnovská, J.; Kazdová, L.; Drahota, Zdeněk; Mráček, Tomáš; Houštěk, Josef

2016-01-01

Roč. 48, č. 6 (2016), s. 420-427 ISSN 1094-8341 R&D Projects: GA MŠk(CZ) LL1204; GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 ; RVO:61389005 Keywords : brown adipose tissue * autocrine * transgenic * spontaneously hypertensive rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.044, year: 2016

Lipidomic Adaptations in White and Brown Adipose Tissue in Response to Exercise Demonstrate Molecular Species-Specific Remodeling

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Francis J. May

2017-02-01

Full Text Available Exercise improves whole-body metabolic health through adaptations to various tissues, including adipose tissue, but the effects of exercise training on the lipidome of white adipose tissue (WAT and brown adipose tissue (BAT are unknown. Here, we utilize MS/MSALL shotgun lipidomics to determine the molecular signatures of exercise-induced adaptations to subcutaneous WAT (scWAT and BAT. Three weeks of exercise training decrease specific molecular species of phosphatidic acid (PA, phosphatidylcholines (PC, phosphatidylethanolamines (PE, and phosphatidylserines (PS in scWAT and increase specific molecular species of PC and PE in BAT. Exercise also decreases most triacylglycerols (TAGs in scWAT and BAT. In summary, exercise-induced changes to the scWAT and BAT lipidome are highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflect selective remodeling in scWAT and BAT of both phospholipids and glycerol lipids in response to exercise training, thus providing a comprehensive resource for future studies of lipid metabolism pathways.

Brown adipose tissue: The heat is on the heart.

Science.gov (United States)

Thoonen, Robrecht; Hindle, Allyson G; Scherrer-Crosbie, Marielle

2016-06-01

The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart. Copyright © 2016 the American Physiological Society.

Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function

DEFF Research Database (Denmark)

Mottillo, Emilio P; Desjardins, Eric M; Crane, Justin D

2016-01-01

Brown (BAT) and white (WAT) adipose tissues play distinct roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a cellular energy sensor, but its role...

In a model of Batten disease, palmitoyl protein thioesterase-1 deficiency is associated with brown adipose tissue and thermoregulation abnormalities.

Directory of Open Access Journals (Sweden)

Alfia Khaibullina

Full Text Available Infantile neuronal ceroid lipofuscinosis (INCL is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1. We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1α and uncoupling protein 1 (Ucp-1 in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1α and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of

Brown adipose tissue (BAT) specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation.

Science.gov (United States)

Weiner, Juliane; Rohde, Kerstin; Krause, Kerstin; Zieger, Konstanze; Klöting, Nora; Kralisch, Susan; Kovacs, Peter; Stumvoll, Michael; Blüher, Matthias; Böttcher, Yvonne; Heiker, John T

2017-06-01

Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology. We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels. Vaspin expression was analyzed in isolated white and brown adipocytes during adipogenesis and in response to adrenergic stimuli. DNA-methylation within the vaspin promoter was analyzed to investigate acute epigenetic changes after cold-exposure in BAT. Our results demonstrate a strong induction of vaspin mRNA and protein expression specifically in BAT of both cold-exposed and high-fat (HF) or high-sugar (HS) fed mice. While obesogenic diets also upregulated hepatic vaspin mRNA levels, cold exposure tended to increase vaspin gene expression of inguinal white adipose tissue (iWAT) depots. Concomitantly, vaspin plasma levels were decreased upon obesogenic or thermogenic triggers. Vaspin expression was increased during adipogenesis but unaffected by sympathetic activation in brown adipocytes. Analysis of vaspin promoter methylation in AT revealed lowest methylation levels in BAT, which were acutely reduced after cold exposure. Our data demonstrate a novel BAT-specific regulation of vaspin gene expression upon physiological stimuli in vivo with acute epigenetic changes that may contribute to cold-induced expression in BAT. We conclude that these findings indicate functional relevance and potentially beneficial effects of vaspin in BAT function.

Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

Science.gov (United States)

Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

2016-09-01

Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Synthesis, radiosynthesis and in vitro evaluation of 18F-Bodipy-C16/triglyceride as a dual modal imaging agent for brown adipose tissue.

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Andreas Paulus

Full Text Available Brown adipose tissue research is in the focus in the field of endocrinology. We designed a dual-modal fluorescent/PET fatty acid based tracer on commercially available Bodipy-C16, which can be synthesized to its corresponding triglyceride and which combines the benefits of fluorescent and PET imaging.Bodipy-C16 was coupled to 1,3-diolein resulting in Bodipy-triglyceride. Bodipy-C16 and Bodipy-triglyceride compounds were radiolabeled with 18F using an 18F/19F exchange reaction to yield a dual-modal imaging molecule. Uptake of radiolabeled and non-labeled Bodipy-C16 and Bodipy-triglyceride was analyzed by fluorescence imaging and radioactive uptake in cultured adipocytes derived from human brown adipose tissue and white adipose tissue.Bodipy-C16 and Bodipy-triglyceride were successfully radiolabeled and Bodipy-C16 showed high shelf life and blood plasma stability (99% from 0-4 h. The uptake of Bodipy-C16 increased over time in cultured adipocytes, which was further enhanced after beta-adrenergic stimulation with norepinephrine. The uptake of Bodipy-C16 was inhibited by oleic acid and CD36 inhibitor sulfosuccinimidyl-oleate. The poor solubility of Bodipy-triglyceride did not allow stability or in vitro experiments.The new developed dual modal fatty acid based tracers Bodipy-C16 and Bodipy-triglyceride showed promising results to stimulate further in vivo evaluation and will help to understand brown adipose tissues role in whole body energy expenditure.

Glycerophosphate-dependent hydrogen peroxide production by brown adipose tissue mitochondria and its activation by ferricyanide

Czech Academy of Sciences Publication Activity Database

Drahota, Zdeněk; Chowdhury, Subir; Floryk, Daniel; Mráček, Tomáš; Wilhelm, J.; Rauchová, Hana; Lenaz, G.; Houštěk, Josef

2002-01-01

Roč. 34, č. 2 (2002), s. 105-113 ISSN 0145-479X R&D Projects: GA MŠk(CZ) OC 918.50; GA ČR(CZ) GA303/00/1658; GA MŠk(CZ) LN00A079 Grant - others:GA UK(CZ) 70/99 Institutional research plan: CEZ:AV0Z5011922 Keywords : ferricyanide * brown adipose tissue * mitochondrial glycerophosphate dehydrogenase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.920, year: 2002

Imaging of Brown Adipose Tissue: State of the Art.

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Sampath, Srihari C; Sampath, Srinath C; Bredella, Miriam A; Cypess, Aaron M; Torriani, Martin

2016-07-01

The rates of diabetes, obesity, and metabolic disease have reached epidemic proportions worldwide. In recent years there has been renewed interest in combating these diseases not only by modifying energy intake and lifestyle factors, but also by inducing endogenous energy expenditure. This approach has largely been stimulated by the recent recognition that brown adipose tissue (BAT)-long known to promote heat production and energy expenditure in infants and hibernating mammals-also exists in adult humans. This landmark finding relied on the use of clinical fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography, and imaging techniques continue to play a crucial and increasingly central role in understanding BAT physiology and function. Herein, the authors review the origins of BAT imaging, discuss current preclinical and clinical strategies for imaging BAT, and discuss imaging methods that will provide crucial insight into metabolic disease and how it may be treated by modulating BAT activity. (©) RSNA, 2016.

Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

Science.gov (United States)

Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

2014-12-01

Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis. © 2014 Wiley Periodicals, Inc.

Role of the autonomic nervous system in activation of human brown adipose tissue: A review of the literature

NARCIS (Netherlands)

Bahler, L.; Molenaars, R. J.; Verberne, H. J.; Holleman, F.

2015-01-01

Brown adipose tissue (BAT) is able to convert calories into heat rather than storing them. Therefore, activated BAT could be a potential target in the battle against obesity and type 2 diabetes. This review focuses on the role of the autonomic nervous system in the activation of human BAT. Although

Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI.

Science.gov (United States)

Hu, Houchun H; Yin, Larry; Aggabao, Patricia C; Perkins, Thomas G; Chia, Jonathan M; Gilsanz, Vicente

2013-10-01

To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. Infants had lower supraclavicular FFs than children (P children exhibited lower supraclavicular FFs and T2* values than overweight children (P children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P children, they were correlated with weight and body mass index (BMI) (P children (P children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity. Copyright © 2013 Wiley Periodicals, Inc.

4E-BP1 regulates the differentiation of white adipose tissue.

Science.gov (United States)

Tsukiyama-Kohara, Kyoko; Katsume, Asao; Kimura, Kazuhiro; Saito, Masayuki; Kohara, Michinori

2013-07-01

4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Lipid profiling of in vitro cell models of adipogenic differentiation: relationships with mouse adipose tissues

OpenAIRE

Liaw, Lucy; Prudovsky, Igor; Koza, Robert A.; Anunciado-Koza, Rea V.; Siviski, Matthew E.; Lindner, Volkhard; Friesel, Robert E.; Rosen, Clifford J.; Baker, Paul R.S.; Simons, Brigitte; Vary, Calvin P.H.

2016-01-01

Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MSALL. Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-...

Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity

Science.gov (United States)

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Zhang, Nan; Szweda, Luke I.; Griffin, Timothy M.; Barlic-Dicen, Jana

2014-01-01

The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role in this tissue remains unknown. We evaluated whether deficiency in either adipocyte or myeloid leukocyte CXCR4 affects body weight (BW) and adiposity in a mouse model of high-fat-diet (HFD)-induced obesity. We found that ablation of adipocyte, but not myeloid leukocyte, CXCR4 exacerbated obesity. The HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control mice, had increased BW (average: 52.0 g vs. 35.5 g), adiposity (average: 49.3 vs. 21.0% of total BW), and inflammatory leukocyte content in white adipose tissue (WAT), despite comparable food intake. As previously reported, HFD feeding increased uncoupling protein 1 (UCP1) expression (fold increase: 3.5) in brown adipose tissue (BAT) of the C57BL/6 control mice. However, no HFD-induced increase in UCP1 expression was observed in the AdCXCR4ko mice, which were cold sensitive. Thus, our study suggests that adipocyte CXCR4 limits development of obesity by preventing excessive inflammatory cell recruitment into WAT and by supporting thermogenic activity of BAT. Since CXCR4 is conserved between mouse and human, the newfound role of CXCR4 in mouse adipose tissue may parallel the role of this chemokine receptor in human adipose tissue.—Yao, L., Heuser-Baker, J., Herlea-Pana, O., Zhang, N., Szweda, L. I., Griffin, T. M., Barlic-Dicen, J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. PMID:25016030

Fish oil intake induces UCP1 upregulation in brown and white adipose tissue via the sympathetic nervous system.

Science.gov (United States)

Kim, Minji; Goto, Tsuyoshi; Yu, Rina; Uchida, Kunitoshi; Tominaga, Makoto; Kano, Yuriko; Takahashi, Nobuyuki; Kawada, Teruo

2015-12-17

Brown adipose tissue (BAT) plays a central role in regulating energy homeostasis, and may provide novel strategies for the treatment of human obesity. BAT-mediated thermogenesis is regulated by mitochondrial uncoupling protein 1 (UCP1) in classical brown and ectopic beige adipocytes, and is controlled by sympathetic nervous system (SNS). Previous work indicated that fish oil intake reduces fat accumulation and induces UCP1 expression in BAT; however, the detailed mechanism of this effect remains unclear. In this study, we investigated the effect of fish oil on energy expenditure and the SNS. Fish oil intake increased oxygen consumption and rectal temperature, with concomitant upregulation of UCP1 and the β3 adrenergic receptor (β3AR), two markers of beige adipocytes, in the interscapular BAT and inguinal white adipose tissue (WAT). Additionally, fish oil intake increased the elimination of urinary catecholamines and the noradrenaline (NA) turnover rate in interscapular BAT and inguinal WAT. Furthermore, the effects of fish oil on SNS-mediated energy expenditure were abolished in transient receptor potential vanilloid 1 (TRPV1) knockout mice. In conclusion, fish oil intake can induce UCP1 expression in classical brown and beige adipocytes via the SNS, thereby attenuating fat accumulation and ameliorating lipid metabolism.

Pronounced expression of the lipolytic inhibitor G0/G1 Switch Gene 2 (G0S2) in adipose tissue from brown bears (Ursus arctos) prior to hibernation

DEFF Research Database (Denmark)

Jessen, Niels; Nielsen, Thomas S; Vendelbo, Mikkel H

2016-01-01

Prior to hibernation, the brown bear (Ursus arctos) exhibits unparalleled weight gain. Unlike humans, weight gain in bears is associated with lower levels of circulating free fatty acids (FFA) and increased insulin sensitivity. Understanding how free-ranging brown bears suppress lipolysis when...... gaining weight may therefore provide novel insight toward the development of human therapies. Blood and subcutaneous adipose tissue were collected from immobilized free-ranging brown bears (fitted with GPS-collars) during hibernation in winter and from the same bears during the active period in summer...... in Dalarna, Sweden. The expression of lipid droplet-associated proteins in adipose tissue was examined under the hypothesis that bears suppress lipolysis during summer while gaining weight by increased expression of negative regulators of lipolysis. Adipose triglyceride lipase (ATGL) expression did...

Decrease of Perivascular Adipose Tissue Browning Is Associated With Vascular Dysfunction in Spontaneous Hypertensive Rats During Aging

Directory of Open Access Journals (Sweden)

Ling-Ran Kong

2018-04-01

Full Text Available Functional perivascular adipose tissue (PVAT is necessary to maintain vascular physiology through both mechanical support and endocrine or paracrine ways. PVAT shows a brown adipose tissue (BAT-like feature and the browning level of PVAT is dependent on the anatomic location and species. However, it is not clear whether PVAT browning is involved in the vascular tone regulation in spontaneously hypertensive rats (SHRs. In the present study, we aimed to illustrate the effect of aging on PVAT browning and subsequent vasomotor reaction in SHRs. Herein we utilized histological staining and western blot to detect the characteristics of thoracic PVAT (tPVAT in 8-week-old and 16-week-old SHR and Wistar-Kyoto (WKY rats. We also detected vascular reactivity analysis to determine the effect of tPVAT on vasomotor reaction during aging. The results showed that tPVAT had a similar phenotype to BAT, including smaller adipocyte size and positive uncoupling protein-1 (UCP1 staining. Interestingly, the tPVAT of 8-week-old SHR showed increased BAT phenotypic marker expression compared to WKY, whereas the browning level of tPVAT had a more dramatic decrease from 8 to 16 weeks of age in SHR than age-matched WKY rats. The vasodilation effect of tPVAT on aortas had no significant difference in 8-week-old WKY and SHR, whereas this effect is obviously decreased in 16-week-old SHR compared to WKY. In contrast, tPVAT showed a similar vasoconstriction effect in 8- or 16-week-old WKY and SHR rats. Moreover, we identified an important vasodilator adenosine, which regulates adipocyte browning and may be a potential PVAT-derived relaxing factor. Adenosine is dramatically decreased from 8 to 16 weeks of age in the tPVAT of SHR. In summary, aging is associated with a decrease of tPVAT browning and adenosine production in SHR rats. These may result in attenuated vasodilation effect of the tPVAT in SHR during aging.

Central GLP-1 receptor signalling accelerates plasma clearance of triacylglycerol and glucose by activating brown adipose tissue in mice

NARCIS (Netherlands)

Kooijman, Sander; Wang, Yanan; Parlevliet, Edwin T.; Boon, Mariëtte R.; Edelschaap, David; Snaterse, Gido; Pijl, Hanno; Romijn, Johannes A.; Rensen, Patrick C. N.

2015-01-01

Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, used in the treatment of type 2 diabetes, has recently been shown to increase thermogenesis via the brain. As brown adipose tissue (BAT) produces heat by burning triacylglycerol (TG) and takes up glucose for de novo lipogenesis, the aim of

Inhibition of the central melanocortin system decreases brown adipose tissue activity

NARCIS (Netherlands)

Kooijman, S.; Boon, M.R.; Parlevliet, E.T.; Geerling, J.J.; Pol, V. van de; Romijn, J.A.; Havekes, L.M.; Meurs, I.; Rensen, P.C.N.

2014-01-01

The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology.

Science.gov (United States)

Louveau, I; Perruchot, M-H; Bonnet, M; Gondret, F

2016-11-01

Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants. In contrast to other tissues, the embryonic origin of adipose cells remains the subject of debate. Adipose cells arise from the recruitment of specific multipotent stem cells/progenitors named adipose tissue-derived stromal cells. Recent studies have highlighted the existence of a variety of those cells being able to differentiate into white, brown or brown-like/beige adipocytes. After commitment to the adipocyte lineage, progenitors undergo large changes in the expression of many genes involved in cell cycle arrest, lipid accumulation and secretory functions. Early nutrition can affect these processes during fetal and perinatal periods and can also influence or pre-determinate later growth of adipose tissue. How these changes may be related to adipose tissue functional maturity around birth and can influence newborn survival is discussed. Altogether, a better knowledge of fetal and postnatal adipose tissue development is important for various aspects of animal production, including neonatal survival, postnatal growth efficiency and health.

Mutant Wars2 gene in spontaneously hypertensive rats impairs brown adipose tissue function and predisposes to visceral obesity

Czech Academy of Sciences Publication Activity Database

Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Trnovská, J.; Škop, V.; Marková, I.; Malínská, H.; Hüttl, M.; Kazdová, L.; Bardová, Kristina; Tauchmannová, Kateřina; Vrbacký, Marek; Nůsková, Hana; Mráček, Tomáš; Kopecký, Jan; Houštěk, Josef

2017-01-01

Roč. 66, č. 6 (2017), s. 917-924 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * spontaneously hypertensive rat * quantitative trait loci * transgenic * Wars2 gene * mitochondrial proteosynthesis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 1.461, year: 2016

Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

DEFF Research Database (Denmark)

Hao, Qin; Yadav, Rachita; Basse, Astrid L.

2015-01-01

We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen...... exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating...

Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

Directory of Open Access Journals (Sweden)

Teresa G. Valencak

2017-08-01

Full Text Available Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders. Keywords: Body fatness, Adipose tissue, Sex-specific differences, Adipokines, Adipocytes, Obesity, Energy metabolism

Respiratory chain components involved in the glycerophosphate dehydrogenase-dependent ROS production by brown adipose tissue mitochondria

Czech Academy of Sciences Publication Activity Database

Vrbacký, Marek; Drahota, Zdeněk; Mráček, Tomáš; Vojtíšková, Alena; Ješina, Pavel; Stopka, Pavel; Houštěk, Josef

2007-01-01

Roč. 1767, č. 7 (2007), s. 989-997 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GA303/06/1261; GA MŠk(CZ) 1M0520 Grant - others:Framework Program EUMITOCOMBAT(XE) LSHM-CT-2004-503116 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z40320502 Source of funding: R - rámcový projekt EK Keywords : brown adipose tissue mitochondria * reactive oxygen species * glycerophosphate dehydrogenase, Subject RIV: CE - Biochemistry Impact factor: 3.835, year: 2007

Docosahexaenoic acid (DHA) at the sn-2 position of triacylglycerols increases DHA incorporation in brown, but not in white adipose tissue, of hamsters.

Science.gov (United States)

Lopes, Paula A; Bandarra, Narcisa M; Martins, Susana V; Madeira, Marta S; Ferreira, Júlia; Guil-Guerrero, José L; Prates, José A M

2018-06-01

We hypothesised that the incorporation of docosahexaenoic acid (DHA) across adipose tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position. Ten-week old male hamsters were allocated to 4 dietary treatments (n = 10): linseed oil (LSO-control group), fish oil (FO), fish oil ethyl esters (FO-EE) and structured DHA at the sn-2 position of TAG (DHA-SL) during 12 weeks. In opposition to the large variations found for fatty acid composition in retroperitoneal white adipose tissue (WAT), brown adipose tissue (BAT) was less responsive to diets. DHA was not found in subcutaneous and retroperitoneal WAT depots but it was successfully incorporated in BAT reaching the highest percentage in DHA-SL. The PCA on plasma hormones (insulin, leptin, adiponectin) and fatty acids discriminated BAT from WATs pointing towards an individual signature on fatty acid deposition, but did not allow for full discrimination of dietary treatments within each adipose tissue.

Pronounced expression of the lipolytic inhibitor G0/G1 Switch Gene 2 (G0S2) in adipose tissue from brown bears (Ursus arctos) prior to hibernation.

Science.gov (United States)

Jessen, Niels; Nielsen, Thomas S; Vendelbo, Mikkel H; Viggers, Rikke; Støen, Ole-Gunnar; Evans, Alina; Frøbert, Ole

2016-04-01

Prior to hibernation, the brown bear (Ursus arctos) exhibits unparalleled weight gain. Unlike humans, weight gain in bears is associated with lower levels of circulating free fatty acids (FFA) and increased insulin sensitivity. Understanding how free-ranging brown bears suppress lipolysis when gaining weight may therefore provide novel insight toward the development of human therapies. Blood and subcutaneous adipose tissue were collected from immobilized free-ranging brown bears (fitted with GPS-collars) during hibernation in winter and from the same bears during the active period in summer in Dalarna, Sweden. The expression of lipid droplet-associated proteins in adipose tissue was examined under the hypothesis that bears suppress lipolysis during summer while gaining weight by increased expression of negative regulators of lipolysis. Adipose triglyceride lipase (ATGL) expression did not differ between seasons, but in contrast, the expression of ATGL coactivator Comparative gene identification-58 (CGI-58) was lower in summer. In addition, the expression of the negative regulators of lipolysis, G0S2 and cell-death inducing DNA fragmentation factor-a-like effector (CIDE)C markedly increased during summer. Free-ranging brown bears display potent upregulation of inhibitors of lipolysis in adipose tissue during summer. This is a potential mechanism for increased insulin sensitivity during weight gain and G0S2 may serve as a target to modulate insulin sensitivity. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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

DEFF Research Database (Denmark)

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

2013-01-01

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

Norepinephrine turnover in brown adipose tissue is stimulated by a single meal

International Nuclear Information System (INIS)

Glick, Z.; Raum, W.J.

1986-01-01

A single meal stimulates brown adipose tissue (BAT) thermogenesis in rats. In the present study the role of norepinephrine in this thermogenic response was assessed from the rate of its turnover in BAT after a single test meal. For comparison, norepinephrine turnover was determined in the heart and spleen. A total of 48 male Wistar rats (200 g) were trained to eat during two feeding sessions per day. On the experimental day, one group (n = 24) was meal deprived and the other (n = 24) was given a low-protein high-carbohydrate test meal for 2 h. The synthesis inhibition method with α-methyl-p-tyrosine was employed to determine norepinephrine turnover from its concentration at four hourly time points after the meal. Tissue concentrations of norepinephrine were determined by radioimmunoassay. Norepinephrine concentration and turnover rate were increased more than threefold in BAT of the meal-fed compared with the meal-deprived rats. Neither were significantly altered by the meal in the heart or spleen. The data suggest that norepinephrine mediates a portion of the thermic effect of meals that originate in BAT

Ontogenesis of muscle and adipose tissues and their interactions in ruminants and other species.

Science.gov (United States)

Bonnet, M; Cassar-Malek, I; Chilliard, Y; Picard, B

2010-07-01

The lean-to-fat ratio, that is, the relative masses of muscle and adipose tissue, is a criterion for the yield and quality of bovine carcasses and meat. This review describes the interactions between muscle and adipose tissue (AT) that may regulate the dynamic balance between the number and size of muscle v. adipose cells. Muscle and adipose tissue in cattle grow by an increase in the number of cells (hyperplasia), mainly during foetal life. The total number of muscle fibres is set by the end of the second trimester of gestation. By contrast, the number of adipocytes is never set. Number of adipocytes increases mainly before birth until 1 year of age, depending on the anatomical location of the adipose tissue. Hyperplasia concerns brown pre-adipocytes during foetal life and white pre-adipocytes from a few weeks after birth. A decrease in the number of secondary myofibres and an increase in adiposity in lambs born from mothers severely underfed during early pregnancy suggest a balance in the commitment of a common progenitor into the myogenic or adipogenic lineages, or a reciprocal regulation of the commitment of two distinct progenitors. The developmental origin of white adipocytes is a subject of debate. Molecular and histological data suggested a possible transdifferentiation of brown into white adipocytes, but this hypothesis has now been challenged by the characterization of distinct precursor cells for brown and white adipocytes in mice. Increased nutrient storage in fully differentiated muscle fibres and adipocytes, resulting in cell enlargement (hypertrophy), is thought to be the main mechanism, whereby muscle and fat masses increase in growing cattle. Competition or prioritization between adipose and muscle cells for the uptake and metabolism of nutrients is suggested, besides the successive waves of growth of muscle v. adipose tissue, by the inhibited or delayed adipose tissue growth in bovine genotypes exhibiting strong muscular development. This

Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

Directory of Open Access Journals (Sweden)

Courtney M. Anderson

2015-02-01

Full Text Available Brown adipose tissue (BAT possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ. While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

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

DEFF Research Database (Denmark)

Elabd, Christian; Chiellini, Chiara; Carmona, Mamen

2009-01-01

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......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......-agonists and atrial natriuretic peptide, and release of adiponectin and leptin. Herein, we show that, upon chronic exposure to a specific PPARgamma but not to a PPARbeta/delta or a PPARalpha agonist, hMADS cell-derived white adipocytes are able to switch to a brown phenotype by expressing both uncoupling protein one...

Molecular imaging of brown adipose tissue in health and disease

International Nuclear Information System (INIS)

Bauwens, Matthias; Wierts, Roel; Brans, Boudewijn; Royen, Bart van; Backes, Walter; Bucerius, Jan; Mottaghy, Felix

2014-01-01

Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, 18 F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to 18 F-FDG, other radiopharmaceuticals such as 99m Tc-sestamibi, 123 I-metaiodobenzylguanidine (MIBG), 18 F-fluorodopa and 18 F-14(R,S)-[ 18 F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

Directory of Open Access Journals (Sweden)

Sung Sik eChoe

2016-04-01

Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

Science.gov (United States)

Moran-Ramos, Sofía; Guerrero-Vargas, Natali N; Mendez-Hernandez, Rebeca; Basualdo, Maria Del Carmen; Escobar, Carolina; Buijs, Ruud M

2017-12-01

What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

International Nuclear Information System (INIS)

Mirbolooki, M. Reza; Upadhyay, Sanjeev Kumar; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

2014-01-01

Objective: Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. Methods: A β 3 -adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [ 18 F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Results: Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [ 18 F]FDG PET images. CL 316243 increased the total [ 18 F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [ 18 F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [ 18 F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU

Brown Adipose Tissue Function Is Enhanced in Long-Lived, Male Ames Dwarf Mice

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McFadden, Samuel; Fang, Yimin; Huber, Joshua A.; Zhang, Chi; Sun, Liou Y.; Bartke, Andrzej

2016-01-01

Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity. PMID:27740871

Carotenoids in Adipose Tissue Biology and Obesity.

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Bonet, M Luisa; Canas, Jose A; Ribot, Joan; Palou, Andreu

2016-01-01

Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition.

Differential effects of Roux-en-Y gastric bypass surgery on brown and beige adipose tissue thermogenesis.

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Hankir, Mohammed K; Bronisch, Felix; Hintschich, Constantin; Krügel, Ute; Seyfried, Florian; Fenske, Wiebke K

2015-10-01

There are numerous reports of increased energy expenditure after Roux-en-Y gastric bypass (RYGB) surgery in humans and rodent models but the underlying mechanisms remain poorly understood. In the present study we assessed at the gene expression level whether RYGB leads to recruitment of brown adipose tissue (BAT) and/or beige adipose tissue (BeAT) as a means of enhanced facultative thermogenesis and increased energy expenditure after surgery. Diet-induced obese male Wistar rats were randomized into RYGB-operated (n=10), sham-operated ad libitum fed (Sham) (n=7) or sham-operated body weight matched (BWM) to RYGB groups (n=7). At a stage of postoperatively stabilized weight reduction, BAT (interscapular), subcutaneous (inguinal) and visceral (epididymal and perirenal) white adipose tissue (WAT) depots were collected in the fasted state. Expression of thermoregulatory genes (UCP1, CIDEA and PRDM16) in BAT and WAT as well as specific markers of BeAT (Ear2 and TMEM26) in WAT was analyzed using RT-qPCR. Compared to Sham rats, UCP1 mRNA expression in BAT was significantly reduced in BWM, but not in RYGB rats. No differences in mRNA expression were found for thermoregulatory proteins or for markers of BeAT in subcutaneous or visceral WAT depots between RYGB and Sham groups. The compensatory decrease in BAT thermogenic gene expression typically associated with body weight loss is attenuated after RYGB which, as opposed to recruitment of BeAT, may contribute to overall increases in energy expenditure and weight loss maintenance after surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential CT Attenuation of Metabolically Active and Inactive Adipose Tissues — Preliminary Findings

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Hu, Houchun H.; Chung, Sandra A.; Nayak, Krishna S.; Jackson, Hollie A.; Gilsanz, Vicente

2010-01-01

This study investigates differences in CT Hounsfield units (HUs) between metabolically active (brown fat) and inactive adipose tissues (white fat) due to variations in their densities. PET/CT data from 101 pediatric and adolescent patients were analyzed. Regions of metabolically active and inactive adipose tissues were identified and standard uptake values (SUVs) and HUs were measured. HUs of active brown fat were more positive (p<0.001) than inactive fat (−62.4±5.3 versus −86.7±7.0) and the difference was observed in both males and females. PMID:21245691

Ghrelin receptor regulates adipose tissue inflammation in aging.

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Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

2016-01-01

Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

Molecular imaging of brown adipose tissue in health and disease

Energy Technology Data Exchange (ETDEWEB)

Bauwens, Matthias [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Maastricht University, Research School NUTRIM, Maastricht (Netherlands); Wierts, Roel; Brans, Boudewijn [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Royen, Bart van; Backes, Walter [MUMC, Department of Medical Imaging, Division of Radiology, Maastricht (Netherlands); Bucerius, Jan [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany); Maastricht University, Research School CARIM, Maastricht (Netherlands); Mottaghy, Felix [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany)

2014-04-15

Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, {sup 18}F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to {sup 18}F-FDG, other radiopharmaceuticals such as {sup 99m}Tc-sestamibi, {sup 123}I-metaiodobenzylguanidine (MIBG), {sup 18}F-fluorodopa and {sup 18}F-14(R,S)-[{sup 18}F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

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Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

2018-01-01

Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

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Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

Modulation of glucose uptake in adipose tissue by nitric oxide ...

Indian Academy of Sciences (India)

Madhu

ion-dependent breakdown and trans-nitrosation reactions are ... [McGrowder D, Ragoobirsingh D and Brown P 2006 Modulation of glucose uptake in adipose tissue by nitric oxide-generating ... Briefly, nicotinamide (Sigma Chemical Co.,.

Suppression of expression of muscle-associated proteins by PPARα in brown adipose tissue

International Nuclear Information System (INIS)

Tong, Yuhong; Hara, Atsushi; Komatsu, Makiko; Tanaka, Naoki; Kamijo, Yuji; Gonzalez, Frank J.; Aoyama, Toshifumi

2005-01-01

Peroxisome proliferator-activated receptor α (PPARα) belongs to the steroid/nuclear receptor superfamily. Two-dimensional (2D) SDS-PAGE analysis of brown adipose tissue (BAT) unexpectedly revealed six spots that were present only in PPARα-null mice. Proteomic analysis indicated that these proteins were tropomyosin-1 α chain, tropomyosin β chain, myosin regulatory light chain 2, myosin light chain 3, and parvalbumin α. Analyses of mRNA have revealed that PPARα suppressed the genes encoding these proteins in a synchronous manner in adult wild-type mice. Histological and physiological analyses of BAT showed in adult wild-type mice, a marked suppression of BAT growth concurrent with a prominent decrease in lipolytic and thermogenesis activities. These results suggest that in adult mice, PPARα functions to suppress the expression of the proteins that may be involved in the architecture of BAT, and thus may function in keeping BAT in a quiescent state

Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis.

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Ohashi, Natsuko; Morino, Katsutaro; Ida, Shogo; Sekine, Osamu; Lemecha, Mengistu; Kume, Shinji; Park, Shi-Young; Choi, Cheol Soo; Ugi, Satoshi; Maegawa, Hiroshi

2017-09-01

Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. O -linked N -acetylglucosamine ( O -GlcNAc) modification is characterized by the addition of N -acetylglucosamine to various proteins by O -GlcNAc transferase (Ogt), subsequently modulating various cellular processes. However, little is known about the role of O -GlcNAc modification in adipose tissues. Here, we report the critical role of O -GlcNAc modification in cold-induced thermogenesis. Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O -GlcNAc modification in BAT is responsible for cold-induced thermogenesis. Hypothermia was significant under fasting conditions. This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. In conclusion, O -GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. Glucose flux into BAT may be a signal to maintain BAT physiological responses. © 2017 by the American Diabetes Association.

Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues.

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Gregory Lacraz

Full Text Available IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues.Control and IL-15 KO mice were maintained on high fat diet (HFD or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells.Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues.Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.

Adipose tissue engineering: state of the art, recent advances and innovative approaches.

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Tanzi, Maria Cristina; Farè, Silvia

2009-09-01

Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice.

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Almind, Katrine; Manieri, Monia; Sivitz, William I; Cinti, Saverio; Kahn, C Ronald

2007-02-13

C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a beta3-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice.

Is It Possible to Detect Activated Brown Adipose Tissue in Humans Using Single-Time-Point Infrared Thermography under Thermoneutral Conditions? Impact of BMI and Subcutaneous Adipose Tissue Thickness.

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Sergios Gatidis

Full Text Available To evaluate the feasibility to detect activated brown adipose tissue (BAT using single-time-point infrared thermography of the supraclavicular skin region under thermoneutral conditions. To this end, infrared thermography was compared with 18-F-FDG PET, the current reference standard for the detection of activated BAT.120 patients were enrolled in this study. After exclusion of 18 patients, 102 patients (44 female, 58 male, mean age 58±17 years were included for final analysis. All patients underwent a clinically indicated 18F-FDG-PET/CT examination. Immediately prior to tracer injection skin temperatures of the supraclavicular, presternal and jugular regions were measured using spatially resolved infrared thermography at room temperature. The presence of activated BAT was determined in PET by typical FDG uptake within the supraclavicular adipose tissue compartments. Local thickness of supraclavicular subcutaneous adipose tissue (SCAT was measured on CT. Measured skin temperatures were statistically correlated with the presence of activated BAT and anthropometric data.Activated BAT was detected in 9 of 102 patients (8.8%. Local skin temperature of the supraclavicular region was significantly higher in individuals with active BAT compared to individuals without active BAT. However, after statistical correction for the influence of BMI, no predictive value of activated BAT on skin temperature of the supraclavicular region could be observed. Supraclavicular skin temperature was significantly negatively correlated with supraclavicular SCAT thickness.We conclude that supraclavicular SCAT thickness influences supraclavicular skin temperature and thus makes a specific detection of activated BAT using single-time-point thermography difficult. Further studies are necessary to evaluate the possibility of BAT detection using alternative thermographic methods, e.g. dynamic thermography or MR-based thermometry taking into account BMI as a confounding factor.

Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1-Deficient Mice.

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Hankir, Mohammed K; Kranz, Mathias; Keipert, Susanne; Weiner, Juliane; Andreasen, Sille G; Kern, Matthias; Patt, Marianne; Klöting, Nora; Heiker, John T; Brust, Peter; Hesse, Swen; Jastroch, Martin; Fenske, Wiebke K

2017-07-01

18 F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18 F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective β3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18 F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy- 3 H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18 F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy- 3 H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18 F-FDG uptake independently of UCP1 thermogenic function. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

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Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

2016-07-26

Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

Quantitation of Brown Adipose Tissue Perfusion in Transgenic Mice Using Near-Infrared Fluorescence Imaging

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Akira Nakayama

2003-01-01

Full Text Available Brown adipose tissue (BAT; brown fat is the principal site of adaptive thermogenesis in the human newborn and other small mammals. Of paramount importance for thermogenesis is vascular perfusion, which controls the flow of cool blood in, and warmed blood out, of BAT. We have developed an optical method for the quantitative imaging of BAT perfusion in the living, intact animal using the heptamethine indocyanine IR-786 and near-infrared (NIR fluorescent light. We present a detailed analysis of the physical, chemical, and cellular properties of IR-786, its biodistribution and pharmacokinetics, and its uptake into BAT. Using transgenic animals with homozygous deletion of Type II iodothyronine deiodinase, or homozygous deletion of uncoupling proteins (UCPs 1 and 2, we demonstrate that BAT perfusion can be measured noninvasively, accurately, and reproducibly. Using these techniques, we show that UCP 1/2 knockout animals, when compared to wild-type animals, have a higher baseline perfusion of BAT but a similar maximal response to β3-receptor agonist. These results suggest that compensation for UCP deletion is mediated, in part, by the control of BAT perfusion. Taken together, BAT perfusion can now be measured noninvasively using NIR fluorescent light, and pharmacological modulators of thermogenesis can be screened at relatively high throughput in living animals.

Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

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Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

2016-06-01

Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Characterization of brown adipose tissue 18F-FDG uptake in PET/CT imaging and its influencing factors in the Chinese population

International Nuclear Information System (INIS)

Shao, Xiaonan; Shao, Xiaoliang; Wang, Xiaosong; Wang, Yuetao

2016-01-01

18 F-FDG PET/CT has been widely applied for tumor imaging. However, it is reported that many normal tissues, e.g., brown adipose tissue, can also uptake 18 F-FDG. The purpose of this study was to determine the imaging characteristics of 18 F-FDG uptake in brown adipose tissue (BAT) in PET/CT. A total of 2,944 patients who underwent PET/CT from September 2011 to March 2013 were analyzed retrospectively. Imaging features of 18 F-FDG uptake in BAT were analyzed. Univariate analysis and logistic regression analysis were performed to evaluate the effect of age, gender, cancer status, body mass index (BMI), average daily maximum temperature of imaging month and fasting plasma glucose (Glu) on the positive rate of 18 F-FDG uptake in BAT. The results showed that 1.9% (57/2944) patients had 18 F-FDG uptake in BAT. 18 F-FDG, manifested as flaky, nodular and beaded shape, was symmetrically distributed in the adipose tissues of cervical and supraclavicular, mediastinal, paravertebral, and perirenal areas. Uptake of 18 F-FDG within cervical/supraclavicular area was most common (89.5%, 51/57) with an SUV max ranging from 2.8 to 31.4. Univariate analysis showed that gender and cancer status were not significantly correlated with the BAT 18 F-FDG uptake rate. In contrast, age, BMI, Glu and average daily maximum temperature in the imaging month were significantly correlated with the BAT 18 F-FDG uptake rate (P < 0.05). Further logistic regression analysis showed that only age, BMI and average daily maximum temperature were significant (OR < 1, P < 0.05). Based on the value of OR, the most significant factor that affects BAT 18 F-FDG uptake rate was age, followed by the average daily maximum temperature and BMI. We concluded that Chinese adult has low positive rate of 18 F-FDG uptake in BAT. Cervical/Supraclavicular is the most common area with BAT 18 F-FDG uptake. Age, average daily maximum temperature and BMI are independent factors affecting 18 F-FDG uptake.

Alcohol, Adipose Tissue and Lipid Dysregulation

Directory of Open Access Journals (Sweden)

Jennifer L. Steiner

2017-02-01

Full Text Available Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long‐term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged. Study of the lipolytic and lipogenic pathways has identified several regulatory proteins modulated by alcohol that contribute to these effects. Glucose tolerance of adipose tissue is also impaired by chronic alcohol due to decreased glucose transporter‐4 availability at the membrane. As an endocrine organ, white adipose tissue (WAT releases several adipokines that are negatively modulated following chronic alcohol consumption including adiponectin, leptin, and resistin. When these effects are combined with the enhanced expression of inflammatory mediators that are induced by chronic alcohol, a proinflammatory state develops within WAT, contributing to the observed lipodystrophy. Lastly, while chronic alcohol intake may enhance thermogenesis of brown adipose tissue (BAT, definitive mechanistic evidence is currently lacking. Overall, both WAT and BAT depots are impacted by chronic alcohol intake and the resulting lipodystrophy contributes to fat accumulation in peripheral organs, thereby enhancing the pathological state accompanying chronic alcohol use disorder.

Perivascular adipose tissue: role in the pathogenesis of obesity, type 2 diabetes mellitus and cardiovascular pathology.

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Tat'yana Ivanovna Romantsova

2015-09-01

Full Text Available Perivascular adipose tissue is a part of blood vessel wall, regulating endovascular homeostasis, endothelial and smooth muscle cells functioning. Under physiological conditions, perivascular tissue provides beneficial anticontractile effect, though undergoes structural and functional changes in obesity, atherosclerosis and diabetes mellitus type2.Collected data suggest the possible key role of perivascular adipose tissue in the pathogenesis of these diseases. Perivascular tissue has been determined as an independent cardiovascular risk factor, regardless of visceral obesity. General mechanisms include a local low-grade inflammation, oxidative stress, tissue renin-angiotensin-aldosterone system activation, paracrine and metabolic alterations. Properties of perivascular adipose tissue depend on the certain type of adipocytes it contains. Brown adipocytes are well known for their metabolic preferences, however it has been shown recently that brown perivascular tissue can contribute to dyslipidemia under some conditions.  The aim of this review is to discuss the current literature understanding of perivascular adipose tissue specifics, changes in its activity, secretory and genetic profilein a course of the most common non-infectious diseases development, as well as molecular mechanisms of its functioning. We also discuss perspectives of target interventions using metabolic pathways and genes of perivascular tissue, for the effective prevention of obesity, diabetes mellitus type2 and cardiovascular diseases.

Fat storage-inducing transmembrane protein 2 is required for normal fat storage in adipose tissue.

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Miranda, Diego A; Kim, Ji-Hyun; Nguyen, Long N; Cheng, Wang; Tan, Bryan C; Goh, Vera J; Tan, Jolene S Y; Yaligar, Jadegoud; Kn, Bhanu Prakash; Velan, S Sendhil; Wang, Hongyan; Silver, David L

2014-04-04

Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo.

Ccl22/MDC, is a prostaglandin dependent pyrogen, acting in the anterior hypothalamus to induce hyperthermia via activation of brown adipose tissue.

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Osborn, Olivia; Sanchez-Alavez, Manuel; Dubins, Jeffrey S; Gonzalez, Alejandro Sanchez; Morrison, Brad; Hadcock, John R; Bartfai, Tamas

2011-03-01

CC Chemokine ligand 22 (Ccl22) is a selective, high affinity ligand at the CC chemokine receptor 4 (Ccr4). We have identified cDNAs encoding both ligand and receptor of the Ccl22-Ccr4 pair in cDNA libraries of the anterior hypothalamus/pre-optic area (AH/POA) by PCR. The AH/POA is the key brain region where endogenous pyrogens have been shown to act on warm sensitive neurons to affect thermogenesis in brown adipose tissue (BAT) and other thermogenically responsive tissues. We show that functional Ccr4 receptors are present in the AH/POA neurons as injection of Ccl22 into the POA but not to other hypothalamic nuclei induces an increase in core body temperature as measured by radiotelemetry. Indomethacin (5 mg/kg s.c) pre-treatment markedly reduced the hyperthermia evoked by POA injection of Ccl22 (10 ng/0.5 ul) and thus suggests that this hyperthermia is mediated through cyclooxygenase activation and thus likely through the formation and action of the pyrogen prostaglandin E2. The temperature elevation involves a decrease in the respiratory exchange ratio and increased activation of the brown adipose tissue as demonstrated by ¹⁸F-FDG-PET imaging. We describe a novel role to the ligand Ccl22 and its receptor Ccr4 in the anterior hypothalamus in temperature regulation that depends on the synthesis of the endogenous pyrogen, prostaglandin E2. Copyright © 2010 Elsevier Ltd. All rights reserved.

RNA-Seq and Mass-Spectrometry-Based Lipidomics Reveal Extensive Changes of Glycerolipid Pathways in Brown Adipose Tissue in Response to Cold

DEFF Research Database (Denmark)

Marcher, Ann-Britt; Loft, Anne; Nielsen, Ronni

2015-01-01

involved in glycerophospholipid synthesis and fatty acid elongation. This is accompanied by significant changes in the acyl chain composition of triacylglycerols (TAGs) as well as subspecies-selective changes of acyl chains in glycerophospholipids. These results indicate that cold adaptation of BAT......Cold exposure greatly alters brown adipose tissue (BAT) gene expression and metabolism to increase thermogenic capacity. Here, we used RNA sequencing and mass-spectrometry-based lipidomics to provide a comprehensive resource describing the molecular signature of cold adaptation at the level...... of the transcriptome and lipidome. We show that short-term (3-day) cold exposure leads to a robust increase in expression of several brown adipocyte genes related to thermogenesis as well as the gene encoding the hormone irisin. However, pathway analysis shows that the most significantly induced genes are those...

Refeeding-induced brown adipose tissue glycogen hyper-accumulation in mice is mediated by insulin and catecholamines.

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Christopher M Carmean

Full Text Available Brown adipose tissue (BAT generates heat during adaptive thermogenesis through a combination of oxidative metabolism and uncoupling protein 1-mediated electron transport chain uncoupling, using both free-fatty acids and glucose as substrate. Previous rat-based work in 1942 showed that prolonged partial fasting followed by refeeding led to a dramatic, transient increase in glycogen stores in multiple fat depots. In the present study, the protocol was replicated in male CD1 mice, resulting in a 2000-fold increase in interscapular BAT (IBAT glycogen levels within 4-12 hours (hr of refeeding, with IBAT glycogen stores reaching levels comparable to fed liver glycogen. Lesser effects occurred in white adipose tissues (WAT. Over the next 36 hr, glycogen levels dissipated and histological analysis revealed an over-accumulation of lipid droplets, suggesting a potential metabolic connection between glycogenolysis and lipid synthesis. 24 hr of total starvation followed by refeeding induced a robust and consistent glycogen over-accumulation similar in magnitude and time course to the prolonged partial fast. Experimentation demonstrated that hyperglycemia was not sufficient to drive glycogen accumulation in IBAT, but that elevated circulating insulin was sufficient. Additionally, pharmacological inhibition of catecholamine production reduced refeeding-induced IBAT glycogen storage, providing evidence of a contribution from the central nervous system. These findings highlight IBAT as a tissue that integrates both canonically-anabolic and catabolic stimulation for the promotion of glycogen storage during recovery from caloric deficit. The preservation of this robust response through many generations of animals not subjected to food deprivation suggests that the over-accumulation phenomenon plays a critical role in IBAT physiology.

Refeeding-Induced Brown Adipose Tissue Glycogen Hyper-Accumulation in Mice Is Mediated by Insulin and Catecholamines

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Carmean, Christopher M.; Bobe, Alexandria M.; Yu, Justin C.; Volden, Paul A.; Brady, Matthew J.

2013-01-01

Brown adipose tissue (BAT) generates heat during adaptive thermogenesis through a combination of oxidative metabolism and uncoupling protein 1-mediated electron transport chain uncoupling, using both free-fatty acids and glucose as substrate. Previous rat-based work in 1942 showed that prolonged partial fasting followed by refeeding led to a dramatic, transient increase in glycogen stores in multiple fat depots. In the present study, the protocol was replicated in male CD1 mice, resulting in a 2000-fold increase in interscapular BAT (IBAT) glycogen levels within 4–12 hours (hr) of refeeding, with IBAT glycogen stores reaching levels comparable to fed liver glycogen. Lesser effects occurred in white adipose tissues (WAT). Over the next 36 hr, glycogen levels dissipated and histological analysis revealed an over-accumulation of lipid droplets, suggesting a potential metabolic connection between glycogenolysis and lipid synthesis. 24 hr of total starvation followed by refeeding induced a robust and consistent glycogen over-accumulation similar in magnitude and time course to the prolonged partial fast. Experimentation demonstrated that hyperglycemia was not sufficient to drive glycogen accumulation in IBAT, but that elevated circulating insulin was sufficient. Additionally, pharmacological inhibition of catecholamine production reduced refeeding-induced IBAT glycogen storage, providing evidence of a contribution from the central nervous system. These findings highlight IBAT as a tissue that integrates both canonically-anabolic and catabolic stimulation for the promotion of glycogen storage during recovery from caloric deficit. The preservation of this robust response through many generations of animals not subjected to food deprivation suggests that the over-accumulation phenomenon plays a critical role in IBAT physiology. PMID:23861810

The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an ¹⁸F-FDG PET/CT Study in the Tropics

OpenAIRE

Huang Yung-Cheng; Chen Tai-Been; Hsu Chien-Chin; Li Shau-Hsuan; Wang Pei-Wen; Lee Bi-Fang; Kuo Ching-Yuan; Chiu Nan-Tsing

2011-01-01

Abstract Background Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low. Methods 18F-FDG PE...

Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity.

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Barquissau, Valentin; Léger, Benjamin; Beuzelin, Diane; Martins, Frédéric; Amri, Ez-Zoubir; Pisani, Didier F; Saris, Wim H M; Astrup, Arne; Maoret, Jean-José; Iacovoni, Jason; Déjean, Sébastien; Moro, Cédric; Viguerie, Nathalie; Langin, Dominique

2018-01-23

Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT). Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity

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Valentin Barquissau

2018-01-01

Full Text Available Caloric restriction (CR is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT. Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity.

Endogenous peripheral hydrogen sulfide is propyretic: its permissive role in brown adipose tissue thermogenesis in rats.

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Soriano, Renato N; Braga, Sara P; Breder, Jéssica S C; Batalhao, Marcelo E; Oliveira-Pelegrin, Gabriela R; Ferreira, Luiz Fernando R; Rocha, Maria José A; Carnio, Evelin C; Branco, Luiz G S

2018-03-01

What is the central question of this study? In fever, the most striking response in the acute phase reaction of systemic inflammation, plasma H 2 S concentration increases. However, the role of endogenous peripheral H 2 S in fever is unknown. What is the main finding and its importance? Endogenous peripheral H 2 S is permissive for increased brown adipose tissue thermogenesis to maintain thermal homeostasis in cold environments as well as to mount fever. This finding expands the physiological role of the gaseous modulator as a key regulator of thermal control in health (thermal homeostasis) and disease (fever in systemic inflammation). In recent years, hydrogen sulfide (H 2 S) has been reported as a gaseous modulator acting in several tissues in health and disease. In animal models of systemic inflammation, the plasma H 2 S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but we found no reports of the peripheral action of H 2 S on this thermoregulatory response. We aimed at investigating whether endogenous systemic H 2 S modulates LPS-induced fever. A temperature datalogger capsule was inserted in the abdominal cavity of male Wistar rats (220-270 g) to record body core temperature. These animals received an i.p. injection of a systemic H 2 S inhibitor (propargylglycine; 50 or 75 mg kg -1 ), immediately followed by an i.p. injection of LPS (50 or 2500 μg kg -1 ), and were exposed to different ambient temperatures (16, 22 or 27°C). At 22°C, but not at 27°C, propargylglycine at 75 mg kg -1 significantly attenuated (P endogenous peripheral H 2 S on brown adipose tissue (BAT) thermogenesis. Evidence on the modulatory role of peripheral H 2 S in BAT thermogenesis was strengthened when we discarded (i) the possible influence of the gas on febrigenic signalling (when measuring plasma cytokines), and (ii) its interaction with the nitric

Metformin lowers plasma triglycerides by promoting VLDL-triglyceride clearance by brown adipose tissue in mice.

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Geerling, Janine J; Boon, Mariëtte R; van der Zon, Gerard C; van den Berg, Sjoerd A A; van den Hoek, Anita M; Lombès, Marc; Princen, Hans M G; Havekes, Louis M; Rensen, Patrick C N; Guigas, Bruno

2014-03-01

Metformin is the first-line drug for the treatment of type 2 diabetes. Besides its well-characterized antihyperglycemic properties, metformin also lowers plasma VLDL triglyceride (TG). In this study, we investigated the underlying mechanisms in APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism. We found that metformin markedly lowered plasma total cholesterol and TG levels, an effect mostly due to a decrease in VLDL-TG, whereas HDL was slightly increased. Strikingly, metformin did not affect hepatic VLDL-TG production, VLDL particle composition, and hepatic lipid composition but selectively enhanced clearance of glycerol tri[(3)H]oleate-labeled VLDL-like emulsion particles into brown adipose tissue (BAT). BAT mass and lipid droplet content were reduced in metformin-treated mice, pointing to increased BAT activation. In addition, both AMP-activated protein kinase α1 (AMPKα1) expression and activity and HSL and mitochondrial content were increased in BAT. Furthermore, therapeutic concentrations of metformin increased AMPK and HSL activities and promoted lipolysis in T37i differentiated brown adipocytes. Collectively, our results identify BAT as an important player in the TG-lowering effect of metformin by enhancing VLDL-TG uptake, intracellular TG lipolysis, and subsequent mitochondrial fatty acid oxidation. Targeting BAT might therefore be considered as a future therapeutic strategy for the treatment of dyslipidemia.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

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T.C. Peixoto

2018-04-01

Full Text Available Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats.

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Peixoto, T C; Moura, E G; Oliveira, E; Younes-Rapozo, V; Soares, P N; Rodrigues, V S T; Santos, T R; Peixoto-Silva, N; Carvalho, J C; Calvino, C; Conceição, E P S; Guarda, D S; Claudio-Neto, S; Manhães, A C; Lisboa, P C

2018-01-01

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

The effect of non-esterified long-chain fatty acids on blood flow and thermogenesis in brown adipose tissue in the young dog

DEFF Research Database (Denmark)

Astrup, A; Bülow, J; Christensen, N J

1985-01-01

In vitro experiments have demonstrated that increasing the molar ratio of extracellular non-esterified fatty acids (NEFA) to albumin stimulates thermogenesis in brown adipocytes. To test these results, in vivo blood flow and local temperature were measured in perirenal brown adipose tissue (BAT...... level. Plasma noradrenaline concentration increased about three-fold and plasma adrenaline concentration about six-fold. The BAT temperature increased by an average of 0.9 degrees C. However, since BAT blood flow was simultaneously reduced by about 50%, it can be calculated that the local heat...... production was also reduced. Consequently, the increase in whole body oxygen consumption was not due to stimulation of BAT thermogenesis. It is concluded that in vivo assessment of BAT thermogenesis requires concomitant measurements of both local BAT temperature and blood flow....

Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white adipose tissue in rat

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Juan Suárez

2014-01-01

Full Text Available β-adrenergic receptor activation promotes brown adipose tissue (BAT β-oxidation and thermogenesis by burning fatty acids during uncoupling respiration. Oleoylethanolamide (OEA can inhibit feeding and stimulate lipolysis by activating peroxisome proliferator-activating receptor-α (PPARα in white adipose tissue (WAT. Here we explore whether PPARα activation potentiates the effect of β3-adrenergic stimulation on energy balance mediated by the respective agonists OEA and CL316243. The effect of this pharmacological association on feeding, thermogenesis, β-oxidation, and lipid and cholesterol metabolism in epididymal (eWAT was monitored. CL316243 (1 mg/kg and OEA (5 mg/kg co-administration over 6 days enhanced the reduction of both food intake and body weight gain, increased the energy expenditure and reduced the respiratory quotient (VCO2/VO2. This negative energy balance agreed with decreased fat mass and increased BAT weight and temperature, as well as with lowered plasma levels of triglycerides, cholesterol, nonessential fatty acids (NEFAs, and the adipokines leptin and TNF-α. Regarding eWAT, CL316243 and OEA treatment elevated levels of the thermogenic factors PPARα and UCP1, reduced p38-MAPK phosphorylation, and promoted brown-like features in the white adipocytes: the mitochondrial (Cox4i1, Cox4i2 and BAT (Fgf21, Prdm16 genes were overexpressed in eWAT. The enhancement of the fatty-acid β-oxidation factors Cpt1b and Acox1 in eWAT was accompanied by an upregulation of de novo lipogenesis and reduced expression of the unsaturated-fatty-acid-synthesis enzyme gene, Scd1. We propose that the combination of β-adrenergic and PPARα receptor agonists promotes therapeutic adipocyte remodelling in eWAT, and therefore has a potential clinical utility in the treatment of obesity.

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

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Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

2015-01-01

Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia – before severe fat loss – in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34–42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

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Suchacki, Karla J; Cawthorn, William P

2018-01-01

The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

The Mechanism of White and Brown Adipocyte Differentiation

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Hironori Nakagami

2013-04-01

Full Text Available Obesity gives vent to many diseases such as type 2 diabetes, hypertension, and hyperlipidemia, being considered as the main causes of mortality and morbidity worldwide. The pathogenesis and pathophysiology of metabolic syndrome can well be understood by studying the molecular mechanisms that control the development and function of adipose tissue. In human body, exist two types of adipose tissue, the white and the brown one, which are reported to play various roles in energy homeostasis. The major and most efficient storage of energy occurs in the form of triglycerides in white adipose tissue while brown adipose tissue actively participates in both basal and inducible energy consumption in the form of thermogenesis. Recent years have observed a rapid and greater interest towards developmental plasticity and therapeutic potential of stromal cells those isolated from adipose tissue. The adipocyte differentiation involves a couple of regulators in the white or brown adipogenesis. Peroxisome proliferators-activated receptor-γ actively participates in regulating carbohydrate and lipid metabolism, and also acts as main regulator of both white and brown adipogenesis. This review based on our recent research, seeks to highlight the adipocyte differentiation.

Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

International Nuclear Information System (INIS)

Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

2013-01-01

Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life

Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

Energy Technology Data Exchange (ETDEWEB)

Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

2013-12-06

Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

Infrared thermography, a new method for detection of brown adipose tissue activity after a meal in humans

Science.gov (United States)

Habek, Nikola; Kordić, Milan; Jurenec, Franjo; Dugandžić, Aleksandra

2018-03-01

The activation of brown adipose tissue (BAT) after cold exposure leads to heat production. However, the activation of BAT activity after a meal as part of diet induced thermogenesis is still controversial. A possible reason is that measuring BAT activity by positron emission tomography-computed tomography (PET CT) via accumulation of radiotracer fludeoxyglucose (18F-FDG), which competes with an increase in glucose concentration after a meal, fails as the method of choice. In this study, activity of BAT was determined by infrared thermography. Activation of BAT 30 min after a meal increases glucose consumption, decreases plasma glucose concentration, and leads to changes of body temperature (diet-induced thermogenesis). Detecting pathophysiological changes in BAT activity after a meal by infrared thermography, a non-invasive more sensitive method, will be of great importance for people with increased body weight and diabetes mellitus type 2.

Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

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van den Berg, Susan M; van Dam, Andrea D; Kusters, Pascal J H; Beckers, Linda; den Toom, Myrthe; van der Velden, Saskia; Van den Bossche, Jan; van Die, Irma; Boon, Mariëtte R; Rensen, Patrick C N; Lutgens, Esther; de Winther, Menno P J

2017-10-01

Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1 expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes. © 2017 Society for Endocrinology.

The Growth of Brown Adipose Tissue in Cold-acclimatized Rats after Depletion of Mast Cell Histamine by Compound 48/80

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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.

Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

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Yumie Morimoto-Kobayashi

Full Text Available Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1 expression in brown adipose tissue (BAT was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA. Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional

Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice.

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Xiong, Xiwen; Zhang, Cuicui; Zhang, Yang; Fan, Rui; Qian, Xinlai; Dong, X Charlie

2017-06-01

SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6- knockout mice generated by the Fabp4-Cre line ( Sirt6 f/f : Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6 f/f :Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line ( Sirt6 f/f :Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis. © 2017 Society for Endocrinology.

3,5-Diiodo-L-thyronine activates brown adipose tissue thermogenesis in hypothyroid rats.

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Assunta Lombardi

Full Text Available 3,5-Diiodo-l-thyronine (T2, a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient and mitochondria (longer lasting, suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis.

Fluoxetine induces lean phenotype in rat by increasing the brown/white adipose tissue ratio and UCP1 expression.

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da Silva, A I; Braz, G R F; Pedroza, A A; Nascimento, L; Freitas, C M; Ferreira, D J S; Manhães de Castro, R; Lagranha, C J

2015-08-01

The serotonergic system plays a crucial role in the energy balance regulation. Energy balance is mediated by food intake and caloric expenditure. Thus, the present study investigated the mechanisms that might be associated with fluoxetine treatment-induced weight reduction. Wistar male rat pups received daily injections with subcutaneous fluoxetine (Fx-group) or vehicle solution (Ct-group) from day 1 until 21 days of age. Several analyses were conducted to verify the involvement of mitochondria in weight reduction. We found that body weight in the Fx-group was lower compared to control. In association to lower fat mass in the Fx-group (25%). Neither neonatal caloric intake nor food intake reveals significant differences. Evaluating caloric expenditure (locomotor activity and temperature after stimulus), we did not observe differences in locomotor activity. However, we observed that the Fx group had a higher capacity to maintain body temperature in a cold environment compared with the Ct-group. Since brown adipose tissue-(BAT) is specialized for heat production and the rate of heat production is related to mitochondrial function, we found that Fx-treatment increases respiration by 36%, although after addition of GDP respiration returned to Ct-levels. Examining ROS production we observe that Fx-group produced less ROS than control group. Evaluating uncoupling protein (UCP) expression we found that Fx-treatment increases the expression by 23%. Taken together, our results suggest that modulation of serotonin system results in positive modulation of UCP and mitochondrial bioenergetics in brown fat tissue.

Development, regulation, metabolism and function of bone marrow adipose tissues.

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Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

2018-05-01

Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks

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Paul de Goede

2018-01-01

Full Text Available The effects of feeding behavior and diet composition, as well as their possible interactions, on daily (clock gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue (WAT, but hardly in other metabolic tissues such as skeletal muscle (SM and brown adipose tissues (BAT. We therefore subjected male Wistar rats to a regular chow or free choice high-fat-high sugar (fcHFHS diet in combination with time restricted feeding (TRF to either the light or dark phase. In SM, all tested clock genes lost their rhythmic expression in the chow light fed group. In the fcHFHS light fed group rhythmic expression for some, but not all, clock genes was maintained, but shifted by several hours. In BAT the daily rhythmicity of clock genes was maintained for the light fed groups, but expression patterns were shifted as compared with ad libitum and dark fed groups, whilst the fcHFHS diet made the rhythmicity of clock genes become more pronounced. Most of the metabolic genes in BAT tissue tested did not show any rhythmic expression in either the chow or fcHFHS groups. In SM Pdk4 and Ucp3 were phase-shifted, but remained rhythmically expressed in the chow light fed groups. Rhythmic expression was lost for Ucp3 whilst on the fcHFHS diet during the light phase. In summary, both feeding at the wrong time of day and diet composition disturb the peripheral clocks in SM and BAT, but to different degrees and thereby result in a further desynchronization between metabolically active tissues such as SM, BAT, WAT and liver.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

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Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

2014-10-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications. © FASEB.

Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice.

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Weiqin Chen

Full Text Available Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/- mice develop lipodystrophy of white adipose tissue (WAT due to unbridled lipolysis. The residual epididymal WAT (EWAT displays a browning phenotype with much smaller lipid droplets (LD and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/- mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/- mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA remodeling. The acyl chains in major species of triacylglyceride (TG and diacylglyceride (DG in the residual EWAT of Bscl2(-/- mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/- adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/- adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.

Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism

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Grgurevic, Lovorka; Christensen, Gitte Lund; Schulz, Tim J

2016-01-01

implicated in pancreas development as well as control of adult glucose homeostasis. Lastly, we review the recently recognized role of BMPs in brown adipose tissue formation and their consequences for energy expenditure and adiposity. In summary, BMPs play a pivotal role in metabolism beyond their role...... homeostasis (anaemia, hemochromatosis) and oxidative damage. The second and third parts of this review focus on BMPs in the development of metabolic pathologies such as type-2 diabetes mellitus and obesity. The pancreatic beta cells are the sole source of the hormone insulin and BMPs have recently been...

Brown adipose tissue activation by rutin ameliorates polycystic ovary syndrome in rat.

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Hu, Tao; Yuan, Xiaoxue; Ye, Rongcai; Zhou, Huiqiao; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Dong, Meng; Huang, Yuanyuan; Lim, Wonchung; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu

2017-09-01

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is characterized by anovulation, hyperandrogenism and polycystic ovary. However, there is a lack of effective treatment for PCOS at present because the pathologic cause of PCOS has not been elucidated. Although it has been known that brown adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT transplantation is not applicable in clinic. Therefore, BAT activation with natural compound could be an effective treatment strategy for PCOS patients. Here, we found that 3 weeks of rutin (a novel compound for BAT activation) treatment increased BAT activation, thereby it improved thermogenesis and systemic insulin sensitivity in dehydroepiandrosterone (DHEA)-induced PCOS rat. In addition, the expression levels of ovarian steroidogenic enzymes such as P450C17, aromatase, 3β-HSD, 17β-HSD and STAR were up-regulated in rutin-treated PCOS rat. Furthermore, acyclicity and the serum level of luteinizing hormone were normalized, and a large number of mature ovulated follicle with a reduction of cystic formation were observed in PCOS rat after rutin treatment. Finally, rutin treatment surprisingly improved fertility and birth defect in PCOS rat. Collectively, our results indicate that rutin treatment significantly improves systemic insulin resistance and ovarian malfunction in PCOS, and our findings in this study provide a novel therapeutic option for the treatment of PCOS by activating BAT with rutin. Copyright © 2017 Elsevier Inc. All rights reserved.

Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis.

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Tupone, Domenico; Madden, Christopher J; Morrison, Shaun F

2014-01-01

From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis.

Subcutaneous inguinal white adipose tissue is responsive to, but dispensable for, the metabolic health benefits of exercise.

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Peppler, Willem T; Townsend, Logan K; Knuth, Carly M; Foster, Michelle T; Wright, David C

2018-01-01

Exercise training has robust effects on subcutaneous inguinal white adipose tissue (iWAT), characterized by a shift to a brown adipose tissue (BAT)-like phenotype. Consistent with this, transplantation of exercise-trained iWAT into sedentary rodents activates thermogenesis and improves glucose homeostasis, suggesting that iWAT metabolism may contribute to the beneficial effects of exercise. However, it is yet to be determined if adaptations in iWAT are necessary for the beneficial systemic effects of exercise. To test this, male C57BL/6 mice were provided access to voluntary wheel running (VWR) or remained as a cage control (SED) for 11 nights after iWAT removal via lipectomy (LIPX) or SHAM surgery. We found that SHAM and LIPX mice with access to VWR ran similar distances and had comparable reductions in body mass, increased food intake, and increased respiratory exchange ratio (RER). Further, VWR improved indexes of glucose homeostasis and insulin tolerance in both SHAM and LIPX mice. The lack of effect of LIPX in the response to VWR was not explained by compensatory increases in markers of mitochondrial biogenesis and thermogenesis in skeletal muscle, epididymal white adipose tissue, or interscapular brown adipose tissue. Together, these data demonstrate that mice with and without iWAT have comparable adaptations to VWR, suggesting that iWAT may be dispensable for the metabolic health benefits of exercise.

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

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So Hun Kim

2016-01-01

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.

Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

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Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

2011-01-01

Research highlights: → Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. → Irbesartan decreased white adipose tissue weight without affecting body weight. → DNA-binding for PPARγ was increased in white adipose tissue in vivo by irbesartan. → Irbesartan increased adipocyte number in white adipose tissue. → Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPARγ agonistic action of an AT 1 receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPARγ in white adipose tissue and the DNA-binding activity of PPARγ in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPARγ and improved adipose tissue dysfunction including insulin resistance.

Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans.

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Blondin, Denis P; Frisch, Frédérique; Phoenix, Serge; Guérin, Brigitte; Turcotte, Éric E; Haman, François; Richard, Denis; Carpentier, André C

2017-02-07

Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11 C-acetate and 18 F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight loss and brown adipose tissue reduction in rat model of sleep apnea

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de Oliveira Patricia G

2008-07-01

Full Text Available Abstract Background - Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS, but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT of Wistar rats. Methods Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle. Results Body weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001. The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054. Conclusion Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT.

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

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Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M; Cisu, Theodore I; Chee, Melissa J; Nguyen, Ngoc L; Zarebidaki, Eleen; Adams, Andrew C; Kharitonenkov, Alexei; Flier, Jeffrey S; Bartness, Timothy J; Maratos-Flier, Eleftheria

2015-07-01

Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.

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Steculorum, Sophie M; Ruud, Johan; Karakasilioti, Ismene; Backes, Heiko; Engström Ruud, Linda; Timper, Katharina; Hess, Martin E; Tsaousidou, Eva; Mauer, Jan; Vogt, Merly C; Paeger, Lars; Bremser, Stephan; Klein, Andreas C; Morgan, Donald A; Frommolt, Peter; Brinkkötter, Paul T; Hammerschmidt, Philipp; Benzing, Thomas; Rahmouni, Kamal; Wunderlich, F Thomas; Kloppenburg, Peter; Brüning, Jens C

2016-03-24

Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanical homeostasis regulating adipose tissue volume

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Svedman Paul

2007-09-01

Full Text Available Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

HIV Persistence in Adipose Tissue Reservoirs.

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Couturier, Jacob; Lewis, Dorothy E

2018-02-01

The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

Regulation of glycolysis in brown adipocytes by HIF-1α

DEFF Research Database (Denmark)

Basse, Astrid L; Isidor, Marie S; Winther, Sally

2017-01-01

Brown adipose tissue takes up large amounts of glucose during cold exposure in mice and humans. Here we report an induction of glucose transporter 1 expression and increased expression of several glycolytic enzymes in brown adipose tissue from cold-exposed mice. Accordingly, these genes were also...... with glucose as the only exogenously added fuel. These data suggest that HIF-1α-dependent regulation of glycolysis is necessary for maximum glucose metabolism in brown adipocytes....

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

Science.gov (United States)

Gao, Mingming; Ma, Yongjie; Liu, Dexi

2015-01-01

High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

Temporal relation between temperature change and FDG uptake in brown adipose tissue

International Nuclear Information System (INIS)

Kim, SunHee; Krynyckyi, Borys R.; Machac, Josef; Kim, Chun K.

2008-01-01

It has been reported that the prevalence of 18 F fluorodeoxyglucose (FDG) uptake in brown adipose tissue (BAT) is related to outdoor temperature, i.e., more frequent during the colder periods of the year. The purpose of this study was to assess the temporal relationship between BAT FDG uptake and temperature. We correlated the prevalence of BAT with average temperatures (divided into five temperature ranges) of seven different durations. One thousand four hundred ninety-five consecutive FDG Positron emission tomography (PET) studies in 1,159 patients (566 male and 593 female, mean age = 60.4 years) were retrospectively reviewed. FDG uptake with distinct patterns compatible with BAT was identified by a consensus of two readers. The local daily average temperature from January 2000 to November 2003 (beginning 60 days before the date of first PET scan) were obtained, and 2-, 3-, 7-, 14-, 30-, and 60-day average temperatures before the date of a PET study were calculated. The prevalence of BAT FDG uptake was correlated with these various average temperatures. The daily, 2-day, 3-day, and 7-day average temperature had an inverse relation with the prevalence of BAT, i.e., the lower the temperature, the higher prevalence of BAT. When the temperature was averaged over 14 days or longer, this inverse relationship between the temperature and the prevalence of BAT was no longer preserved. Our data suggest that increased FDG uptake in BAT occurs more often as an acute response to cold weather (1-7 days) rather than to prolonged periods of average cold weather. (orig.)

Innate immunity orchestrates adipose tissue homeostasis.

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Lin, Yi-Wei; Wei, Li-Na

2017-06-23

Obesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.

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Marcondes, Rodrigo R; Maliqueo, Manuel; Fornes, Romina; Benrick, Anna; Hu, Min; Ivarsson, Niklas; Carlström, Mattias; Cushman, Samuel W; Stenkula, Karin G; Maciel, Gustavo A R; Stener-Victorin, Elisabet

2017-06-15

Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

The Adipose Tissue in Farm Animals

DEFF Research Database (Denmark)

Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura

2014-01-01

and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance...... in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal...... and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in farm animal adipose tissue proteomics, mainly in cattle and pigs, but also in poultry, i.e. chicken and in farmed fish. Proteomics...

Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis

Science.gov (United States)

Tupone, Domenico; Madden, Christopher J.; Morrison, Shaun F.

2014-01-01

From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis. PMID:24570653

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

Energy Technology Data Exchange (ETDEWEB)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

Is epicardial adipose tissue, assessed by echocardiography, a reliable method for visceral adipose tissue prediction?

Science.gov (United States)

Silaghi, Alina Cristina; Poantă, Laura; Valea, Ana; Pais, Raluca; Silaghi, Horatiu

2011-03-01

Epicardial adipose tissue is an ectopic fat storage at the heart surface in direct contact with the coronary arteries. It is considered a metabolically active tissue, being a local source of pro-inflammatory factors that contribute to the pathogenesis of coronary artery disease. The AIM of our study was to establish correlations between echocardiographic assessment of epicardial adipose tissue and anthropometric and ultrasound measurements of the central and peripheral fat depots. The study was conducted on 22 patients with or without coronaropathy. Epicardial adipose tissue was measured using Aloka Prosound α 10 machine with a 3.5-7.5 MHz variable-frequency transducer and subcutaneous and visceral fat with Esaote Megas GPX machine and 3.5-7.5 MHz variable frequency transducer. Epicardial adipose tissue measured by echocardiography is correlated with waist circumference (p < 0.05), visceral adipose tissue thickness measured by ultrasonography (US) and is not correlated with body mass index (p = 0.315), hip and thigh circumference or subcutaneous fat thickness measured by US. Our study confirms that US assessment of epicardial fat correlates with anthropometric and US measurements of the central fat, representing an indirect but reliable marker of the visceral fat.

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

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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

Adipose Tissue Biology: An Update Review

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Anna Meiliana

2009-12-01

Full Text Available BACKGROUND: Obesity is a major health problem in most countries in the world today. It increases the risk of diabetes, heart disease, fatty liver and some form of cancer. Adipose tissue biology is currently one of the “hot” areas of biomedical science, as fundamental for the development of novel therapeutics for obesity and its related disorders.CONTENT: Adipose tissue consist predominantly of adipocytes, adipose-derived stromal cells (ASCs, vascular endothelial cells, pericytes, fibroblast, macrophages, and extracellular matrix. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissue to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. Obesity causes adipose tissue dysfunction and results in obesity-related disorders. SUMMARY: It is now clear that adipose tissue is a complex and highly active metabolic and endocrine organ. Undestanding the molecular mechanisms underlying obesity and its associated disease cluster is also of great significance as the need for new and more effective therapeutic strategies is more urgent than ever.  KEYWORDS: obesity, adipocyte, adipose, tissue, adipogenesis, angiogenesis, lipid droplet, lipolysis, plasticity, dysfunction.

Advances in Adipose-Derived Stem Cells Isolation, Characterization, and Application in Regenerative Tissue Engineering

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Umesh D. Wankhade

2016-01-01

Full Text Available Obesity is a complex, multifactorial disease that has been extensively researched in recent times. Obesity is characterized by excess deposition of adipose tissue in response to surplus energy. Despite the negative connotations of adipose tissue (AT, it serves as a critical endocrine organ. Adipose tissue is a source of several adipokines and cytokines which have been deemed important for both normal metabolic function and disease formation. The discoveries of metabolically active brown AT in adult humans and adipose tissue derived stem cells (ADSC have been key findings in the past decade with potential therapeutic implications. ADSCs represent an enticing pool of multipotent adult stem cells because of their noncontroversial nature, relative abundance, ease of isolation, and expandability. A decade and a half since the discovery of ADSCs, the scientific community is still working to uncover their therapeutic potential in a wide range of diseases. In this review, we provide an overview of the recent developments in the field of ADSCs and examine their potential use in transplantation and cell-based therapies for the regeneration of diseased organs and systems. We also hope to provide perspective on how to best utilize this readily available, powerful pool of stem cells in the future.

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

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Mingming Gao

Full Text Available High-fat diet (HFD has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota.

Science.gov (United States)

Li, Guolin; Xie, Cen; Lu, Siyu; Nichols, Robert G; Tian, Yuan; Li, Licen; Patel, Daxeshkumar; Ma, Yinyan; Brocker, Chad N; Yan, Tingting; Krausz, Kristopher W; Xiang, Rong; Gavrilova, Oksana; Patterson, Andrew D; Gonzalez, Frank J

2017-10-03

While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. Published by Elsevier Inc.

Thioesterase superfamily member 1 suppresses cold thermogenesis by limiting the oxidation of lipid droplet-derived fatty acids in brown adipose tissue

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Kosuke Okada

2016-05-01

Full Text Available Objective: Non-shivering thermogenesis in brown adipose tissue (BAT plays a central role in energy homeostasis. Thioesterase superfamily member 1 (Them1, a BAT-enriched long chain fatty acyl-CoA thioesterase, is upregulated by cold and downregulated by warm ambient temperatures. Them1−/− mice exhibit increased energy expenditure and resistance to diet-induced obesity and diabetes, but the mechanistic contribution of Them1 to the regulation of cold thermogenesis remains unknown. Methods: Them1−/− and Them1+/+ mice were subjected to continuous metabolic monitoring to quantify the effects of ambient temperatures ranging from thermoneutrality (30 °C to cold (4 °C on energy expenditure, core body temperature, physical activity and food intake. The effects of Them1 expression on O2 consumption rates, thermogenic gene expression and lipolytic protein activation were determined ex vivo in BAT and in primary brown adipocytes. Results: Them1 suppressed thermogenesis in mice even in the setting of ongoing cold exposure. Without affecting thermogenic gene transcription, Them1 reduced O2 consumption rates in both isolated BAT and primary brown adipocytes. This was attributable to decreased mitochondrial oxidation of endogenous but not exogenous fatty acids. Conclusions: These results show that Them1 may act as a break on uncontrolled heat production and limit the extent of energy expenditure. Pharmacologic inhibition of Them1 could provide a targeted strategy for the management of metabolic disorders via activation of brown fat. Keywords: Energy expenditure, Fatty acyl-CoA, Acyl-CoA thioesterase, Mitochondria, Obesity

WJD 5th Anniversary Special Issues（1）: Insulin Benefits of healthy adipose tissue in the treatment of diabetes

Institute of Scientific and Technical Information of China (English)

Subhadra; C; Gunawardana

2014-01-01

achieve glucose homeostasis with endogenously-generated adipokines through transplantation or regeneration of healthy adipose tissue.Our recent studies on mouse models show that type 1 diabetes can be reversed without insulin through subcutaneous transplantation of embryonic brown adipose tissue,which leads to replenishment of recipients’white adipose tissue;increase of a number of beneficial adipokines;and fast and long-lasting euglycemia.Insulin-independent glucose homeostasis is established through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue.Transplantation of healthy white adipose tissue is reported to alleviate type 2 diabetes in rodent models on several occasions,and increasing the content of endogenous brown adipose tissue is known to combat obesity and type 2 diabetes in both humans and animal models.While the underlying mechanisms are not fully documented,the beneficial effects of healthy adipose tissue in improving metabolism are increasingly reported,and are worthy of attention as a powerful tool in combating metabolic disease.

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

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Joan Villarroya

Full Text Available Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT and brown (BAT adipose tissues in thymidine kinase 2 (Tk2 H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues.

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

Science.gov (United States)

Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

2011-01-01

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. © 2011 Villarroya et al.

Responsiveness to Thyroid Hormone and to Ambient Temperature Underlies Differences Between Brown Adipose Tissue and Skeletal Muscle Thermogenesis in a Mouse Model of Diet-Induced Obesity

Science.gov (United States)

Ueta, Cintia B.; Olivares, Emerson L.

2011-01-01

Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroid hormone in the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but not brown adipose tissue thermogenic programs, without affecting daily EE. Only at thermoneutrality (30 C) did hypothyroid mice exhibit slower rate of EE, indicating a metabolic response to hypothyroidism that depends on ambient temperature. A byproduct of this mechanism is that at room temperature (22 C), hypothyroid mice are protected against diet-induced obesity, i.e. only at thermoneutrality did hypothyroid mice become obese when placed on a high-fat diet (HFD). This is in contrast to euthyroid controls, which on a HFD gained more body weight and fat at any temperature while activating the brown adipose tissue and accelerating daily EE but not the skeletal muscle thermogenic program. In the liver of euthyroid controls, HFD caused an approximately 5-fold increase in triglyceride content and expression of key metabolic genes, whereas acclimatization to 30 C cut triglyceride content by half and normalized gene expression. However, in hypothyroid mice, HFD-induced changes in liver persisted at 30 C, resulting in marked liver steatosis. Acclimatization to thermoneutrality dramatically improves glucose homeostasis, but this was not affected by hypothyroidism. In conclusion, hypothyroid mice are metabolically sensitive to environmental temperature, constituting a mechanism that defines resistance to diet-induced obesity and hepatic lipid metabolism. PMID:21771890

Phenylalanine kinetics in human adipose tissue.

OpenAIRE

Coppack, S W; Persson, M; Miles, J M

1996-01-01

Very little is known about the regulation of protein metabolism in adipose tissue. In this study systemic, adipose tissue, and forearm phenylalanine kinetics were determined in healthy postabsorptive volunteers before and during a 2-h glucose infusion (7 mg.kg-1.min-1). [3H]Phenylalanine was infused and blood was sampled from a radial artery, a subcutaneous abdominal vein, and a deep forearm vein. Adipose tissue and forearm blood flow were measured with 133Xe and plethysmography, respectively...

Efficient Isolation of Cardiac Stem Cells from Brown Adipose

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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.

Hot heads & cool bodies: The conundrums of human brown adipose tissue (BAT) activity research.

Science.gov (United States)

Bahler, Lonneke; Holleman, Frits; Booij, Jan; Hoekstra, Joost B; Verberne, Hein J

2017-05-01

Brown adipose tissue is able to increase energy expenditure by converting glucose and fatty acids into heat. Therefore, BAT is able to increase energy expenditure and could thereby facilitate weight loss or at least weight maintenance. Since cold is a strong activator of BAT, most prospective research is performed during cold to activate BAT. In current research, there are roughly two methods of cooling. Cooling by lowering ambient air temperature, which uses a fixed temperature for all subjects and personalized cooling, which uses cooling blankets or vests with temperatures that can be adjusted to the individual set point of shivering. These methods might trigger mechanistically different cold responses and hence result in a different BAT activation. This hypothesis is underlined by two studies with the same research question (difference in BAT activity between Caucasians and South Asians) one study found no differences in BAT activity whereas the other did found differences in BAT activity. Since most characteristics (e.g. age, BMI) were similar in the two studies, the best explanation for the differences in outcomes is the use of different cooling protocols. One of the reasons for differences in outcomes might be the sensory input from the facial skin, which might be important for the activation of BAT. In this review we will elaborate on the differences between the two cooling protocols used to activate BAT. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting.

Science.gov (United States)

Hatting, Maximilian; Rines, Amy K; Luo, Chi; Tabata, Mitsuhisa; Sharabi, Kfir; Hall, Jessica A; Verdeguer, Francisco; Trautwein, Christian; Puigserver, Pere

2017-02-07

A promising approach to treating obesity is to increase diet-induced thermogenesis in brown adipose tissue (BAT), but the regulation of this process remains unclear. Here we find that CDC-like kinase 2 (CLK2) is expressed in BAT and upregulated upon refeeding. Mice lacking CLK2 in adipose tissue exhibit exacerbated obesity and decreased energy expenditure during high-fat diet intermittent fasting. Additionally, tissue oxygen consumption and protein levels of UCP1 are reduced in CLK2-deficient BAT. Phosphorylation of CREB, a transcriptional activator of UCP1, is markedly decreased in BAT cells lacking CLK2 due to enhanced CREB dephosphorylation. Mechanistically, CREB dephosphorylation is rescued by the inhibition of PP2A, a phosphatase that targets CREB. Our results suggest that CLK2 is a regulatory component of diet-induced thermogenesis in BAT through increased CREB-dependent expression of UCP1. Copyright © 2017 Elsevier Inc. All rights reserved.

Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with [1-14C]2-deoxyglucose

International Nuclear Information System (INIS)

Cooney, G.J.; Astbury, L.D.; Williams, P.F.; Caterson, I.D.

1987-01-01

The dose-response characteristics of several glucose-utilizing tissues (brain, heart, white adipose tissue, brown adipose tissue, and quadriceps muscle) to a single injection of insulin have been compared in control mice and mice made obese with a single injection of gold thioglucose (GTG). Tissue content of [1- 14 C]2-deoxyglucose 6-phosphate and blood disappearance rate of [1- 14 C]2-deoxyglucose (2-DG) were measured at nine different insulin doses and used to calculate rates of 2-DG uptake and phosphorylation in tissues from control and obese mice. The insulin sensitivity of tissues reflected in the ED50 of insulin response varied widely, and brown adipose tissue was the most insulin-sensitive tissue studied. In GTG-obese mice, heart, quadriceps, and brown adipose tissue were insulin resistant (demonstrated by increased ED50), whereas in white adipose tissue, 2-DG phosphorylation was more sensitive to insulin. Brain 2-DG phosphorylation was insulin independent in control and obese animals. The largest decrease in insulin sensitivity in GTG-obese mice was observed in brown adipose tissue. The loss of diet-induced thermogenesis in brown adipose tissue as a result of the hypothalamic lesion in GTG-obese mice could be a major cause of insulin resistance in brown adipose tissue. Because brown adipose tissue can make a major contribution to whole-body glucose utilization, insulin resistance in this tissue may have a significant effect on whole-animal glucose homeostasis in GTG-obese mice

Noncanonical Wnt signaling promotes obesity-induced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion.

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Fuster, José J; Zuriaga, María A; Ngo, Doan Thi-Minh; Farb, Melissa G; Aprahamian, Tamar; Yamaguchi, Terry P; Gokce, Noyan; Walsh, Kenneth

2015-04-01

Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Concentration of rat brown adipose tissue uncoupling protein may not be correlated with 3H-GDP binding

International Nuclear Information System (INIS)

Henningfield, M.F.; Swick, A.G.; Swick, R.W.

1986-01-01

Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial 3 H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 27 0 C although 3 H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although 3 H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria

Review Analysis of the Association between the Prevalence of Activated Brown Adipose Tissue and Outdoor Temperature

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Yung-Cheng Huang

2012-01-01

Full Text Available Brown adipose tissue (BAT is important for regulating body weight. Environmental temperature influences BAT activation. Activated BAT is identifiable using F18-fluorodeoxyglucose positron emission tomography/computed tomography (F18-FDG PET/CT. F18-FDG PET/CT scans done between June 2005 and May 2009 in our institution in tropical southern Taiwan and BAT studies from PubMed (2002–2011 were reviewed, and the average outdoor temperatures during the study periods were obtained. A simple linear regression was used to analyze the association between the prevalence of activated BAT (P and the average outdoor temperature (T. The review analysis for 9 BAT studies (n=16,765 showed a significant negative correlation (r=-0.741, P=0.022 between the prevalence of activated BAT and the average outdoor temperature. The equation of the regression line is P(%=6.99−0.20×T  (C∘. The prevalence of activated BAT decreased by 1% for each 5C∘ increase in average outdoor temperature. In a neutral ambient temperature, the prevalence of activated BAT is low and especially rare in the tropics. There is a significant linear negative correlation between the prevalence of activated BAT and the average outdoor temperature.

Injectable biomaterials for adipose tissue engineering

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Young, D A; Christman, K L

2012-01-01

Adipose tissue engineering has recently gained significant attention from materials scientists as a result of the exponential growth of soft tissue filler procedures being performed within the clinic. While several injectable materials are currently being marketed for filling subcutaneous voids, they often face limited longevity due to rapid resorption. Their inability to encourage natural adipose formation or ingrowth necessitates repeated injections for a prolonged effect and thus classifies them as temporary fillers. As a result, a significant need for injectable materials that not only act as fillers but also promote in vivo adipogenesis is beginning to be realized. This paper will discuss the advantages and disadvantages of commercially available soft tissue fillers. It will then summarize the current state of research using injectable synthetic materials, biopolymers and extracellular matrix-derived materials for adipose tissue engineering. Furthermore, the successful attributes observed across each of these materials will be outlined along with a discussion of the current difficulties and future directions for adipose tissue engineering. (paper)

PHYSIOLOGICAL ACTIVITY OF THE BROWN ADIPOSE TISSUE.

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Studies were performed to clarify the influence of various factors which might be involved in vascular regulation. Topical application of lidocain ...and treatment with reserpine effectively blocked, while denervation of brown fat, syrosingopine and atropine were ineffective to prevent the blood flow

Loss of ADAMTS5 enhances brown adipose tissue mass and promotes browning of white adipose tissue via CREB signaling

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Dries Bauters

2017-07-01

Conclusions: These data indicate that ADAMTS5 plays a functional role in development of BAT and browning of WAT. Hence, selective targeting of ADAMTS5 could provide a novel therapeutic strategy for treatment/prevention of obesity and metabolic diseases.

Activation of classical brown adipocytes in the adult human perirenal depot is highly correlated with PRDM16-EHMT1 complex expression.

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Gaku Nagano

Full Text Available Brown fat generates heat to protect against cold and obesity. Adrenergic stimulation activates the thermogenic program of brown adipocytes. Although the bioactivity of brown adipose tissue in adult humans had been assumed to very low, several studies using positron emission tomography-computed tomography (PET-CT have detected bioactive brown adipose tissue in adult humans under cold exposure. In this study, we collected adipose tissues obtained from the perirenal regions of adult patients with pheochromocytoma (PHEO or non-functioning adrenal tumors (NF. We demonstrated that perirenal brown adipocytes were activated in adult patients with PHEO. These cells had the molecular characteristics of classical brown fat rather than those of beige/brite fat. Expression of brown adipose tissue markers such as uncoupling protein 1 (UCP1 and cell death-inducing DFFA-like effector A (CIDEA was highly correlated with the amounts of PRD1-BF-1-RIZ1 homologous domain-containing protein-16 (PRDM16 - euchromatic histone-lysine N-methyltransferase 1 (EHMT1 complex, the key transcriptional switch for brown fat development. These results provide novel insights into the reconstruction of human brown adipocytes and their therapeutic application against obesity and its complications such as type 2 diabetes.

Adipose tissue-derived stem cells in oral mucosa tissue engineering ...

African Journals Online (AJOL)

Jane

2011-10-10

Oct 10, 2011 ... stem cells (ADSCs) may play an important role in this field. In this research ..... Adipose tissue is derived from embryonic mesodermal precursors and .... Clonogenic multipotent stem cells in human adipose tissue differentiate ...

Deletion of Nhlh2 results in a defective torpor response and reduced Beta adrenergic receptor expression in adipose tissue.

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Umesh D Wankhade

2010-08-01

Full Text Available Mice with a targeted deletion of the basic helix-loop-helix transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2, display adult-onset obesity with significant increases in their fat depots, abnormal responses to cold exposure, and reduced spontaneous physical activity levels. These phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2 knockout (N2KO mouse a useful model to study the role of central nervous system (CNS control on peripheral tissue such as adipose tissue.Differences in body temperature and serum analysis of leptin were performed in fasted and ad lib fed wild-type (WT and N2KO mice. Histological analysis of white (WAT and brown adipose tissue (BAT was performed. Gene and protein level expression of inflammatory and metabolic markers were compared between the two genotypes.We report significant differences in serum leptin levels and body temperature in N2KO mice compared with WT mice exposed to a 24-hour fast, suggestive of a defect in both white (WAT and brown adipose tissue (BAT function. As compared to WT mice, N2KO mice showed increased serum IL-6 protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of mRNA for several macrophage markers, including expression of macrophage specific protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the mutant animals. The mRNAs for beta3-adrenergic receptors (beta3-AR, beta2-AR and uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice compared with WT mice.These studies implicate Nhlh2 in the central control of WAT and BAT function, with lack of Nhlh2 leading to adipose inflammation and altered gene expression, impaired leptin response to fasting, all suggestive of a deficient torpor response in mutant animals.

Increased in vivo glucose utilization in 30-day-old obese Zucker rat: Role of white adipose tissue

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Krief, S.; Bazin, R.; Dupuy, F.; Lavau, M.

1988-01-01

In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3- 3 H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia. In obese compared with lean rats, tissue glucose uptake was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart in proximal intestine, and in total muscular mass of limbs. The data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake

Tribbles 3 inhibits brown adipocyte differentiation and function by suppressing insulin signaling

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Jeong, Ha-Won; Choi, Ran Hee; McClellan, Jamie L. [Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, SC 29208 (United States); Piroli, Gerardo G.; Frizzell, Norma [Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Tseng, Yu-Hua; Goodyear, Laurie J. [Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215 (United States); Koh, Ho-Jin, E-mail: kohh@mailbox.sc.edu [Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, SC 29208 (United States)

2016-02-19

Recent studies have demonstrated that adult humans have substantial amounts of functioning brown adipose tissue (BAT). Since BAT has been implicated as an anti-obese and anti-diabetic tissue, it is important to understand the signaling molecules that regulate BAT function. There has been a link between insulin signaling and BAT metabolism as deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function. Tribbles 3 (TRB3) is a pseudo kinase that has been shown to regulate metabolism and insulin signaling in multiple tissues but the role of TRB3 in BAT has not been studied. In this study, we found that TRB3 expression was present in BAT and overexpression of TRB3 in brown preadipocytes impaired differentiation and decreased expression of BAT markers. Furthermore, TRB3 overexpression resulted in significantly lower oxygen consumption rates for basal and proton leakage, indicating decreased BAT activity. Based on previous studies showing that deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function, we assessed insulin signaling in brown preadipocytes and BAT in vivo. Overexpression of TRB3 in cells impaired insulin-stimulated IRS1 and Akt phosphorylation, whereas TRB3KO mice displayed improved IRS1 and Akt phosphorylation. Finally, deletion of IRS1 abolished the function of TRB3 to regulate BAT differentiation and metabolism. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function. - Highlights: • TRB3 is expressed in brown adipose tissue and its expression is increased during differentiation. • Overexpression of TRB3 inhibits differentiation and its activity. • Overexpression of TRB3 in brown preadipocytes inhibits insulin signaling. • TRB3KO mice displays improved insulin signaling in brown adipose tissue. • Insulin signaling is required for the effects of TRB3 to regulate brown adipose tissue differentiation and

Tribbles 3 inhibits brown adipocyte differentiation and function by suppressing insulin signaling

International Nuclear Information System (INIS)

Jeong, Ha-Won; Choi, Ran Hee; McClellan, Jamie L.; Piroli, Gerardo G.; Frizzell, Norma; Tseng, Yu-Hua; Goodyear, Laurie J.; Koh, Ho-Jin

2016-01-01

Recent studies have demonstrated that adult humans have substantial amounts of functioning brown adipose tissue (BAT). Since BAT has been implicated as an anti-obese and anti-diabetic tissue, it is important to understand the signaling molecules that regulate BAT function. There has been a link between insulin signaling and BAT metabolism as deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function. Tribbles 3 (TRB3) is a pseudo kinase that has been shown to regulate metabolism and insulin signaling in multiple tissues but the role of TRB3 in BAT has not been studied. In this study, we found that TRB3 expression was present in BAT and overexpression of TRB3 in brown preadipocytes impaired differentiation and decreased expression of BAT markers. Furthermore, TRB3 overexpression resulted in significantly lower oxygen consumption rates for basal and proton leakage, indicating decreased BAT activity. Based on previous studies showing that deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function, we assessed insulin signaling in brown preadipocytes and BAT in vivo. Overexpression of TRB3 in cells impaired insulin-stimulated IRS1 and Akt phosphorylation, whereas TRB3KO mice displayed improved IRS1 and Akt phosphorylation. Finally, deletion of IRS1 abolished the function of TRB3 to regulate BAT differentiation and metabolism. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function. - Highlights: • TRB3 is expressed in brown adipose tissue and its expression is increased during differentiation. • Overexpression of TRB3 inhibits differentiation and its activity. • Overexpression of TRB3 in brown preadipocytes inhibits insulin signaling. • TRB3KO mice displays improved insulin signaling in brown adipose tissue. • Insulin signaling is required for the effects of TRB3 to regulate brown adipose tissue differentiation and

Intrinsic circannual regulation of brown adipose tissue form and function in tune with hibernation.

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Hindle, Allyson G; Martin, Sandra L

2014-02-01

Winter hibernators repeatedly cycle between cold torpor and rewarming supported by nonshivering thermogenesis in brown adipose tissue (BAT). In contrast, summer animals are homeotherms, undergoing reproduction, growth, and fattening. This life history confers variability to BAT recruitment and activity. To address the components underlying prewinter enhancement and winter activation, we interrogated the BAT proteome in 13-lined ground squirrels among three summer and five winter states. We also examined mixed physiology in fall and spring individuals to test for ambient temperature and seasonal effects, as well as the timing of seasonal transitions. BAT form and function differ circannually in these animals, as evidenced by morphology and proteome dynamics. This intrinsic pattern distinguished homeothermic groups and early vs. late winter hibernators. Homeothermic variation derived from postemergence delay in growth and substrate biosynthesis. The heterothermic proteome varied less despite extreme winter physiological shifts and was optimized to exploit lipids by enhanced fatty acid binding, β-oxidation, and mitochondrial protein translocation. Surprisingly, ambient temperature did not affect the BAT proteome during transition seasons; rather, the pronounced summer-winter shift preceded environmental changes and phenotypic progression. During fall transition, differential regulation of two fatty acid binding proteins provides further evidence of recruitment and separates proteomic preparation from successful hibernation. Abundance of FABP4 correlates with torpor bout length throughout the year, clarifying its potential function in hibernation. Metabolically active BAT is a target for treating human obesity and metabolic disorders. Understanding the hibernator's extreme and seasonally distinct recruitment and activation control strategies offers untapped potential to identify novel, therapeutically relevant regulatory pathways.

Adipose tissue as an endocrine organ.

Science.gov (United States)

McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

2014-02-01

Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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Jo, Dong Hyun; Park, Sung Wook; Cho, Chang Sik; Powner, Michael B; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

2015-01-01

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.

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

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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.

Alpha-1 adrenoceptors in brown adipose tissue of lean and ob/ob mice

International Nuclear Information System (INIS)

Behrens-Zaror, G.; Himms-Hagen, J.

1986-01-01

Obese (ob/ob) mice have a low capacity to increase thyroxine 5'-deiodinase (T4 5'-D) in brown adipose tissue (BAT) when exposed to cold. This effect is mediated by alpha-1 (A-1) adrenoceptors. The authors objective was to find out whether BAT of the ob/ob mouse has normal A-1 receptors. Saturation analysis of binding of [3H]-WB4101 at 0.05 nM to 10 μM to crude membrane preparations (100,000 g pellets from Polytron homogenates) using the LIGAND program of Munson and Rodbard, showed two populations of binding sites in BAT of lean (+/+, 11-15 wk old) mice. Acute exposure (12 h, 14 0 C) or acclimation to cold (3 wk, 14 0 C) did not alter affinity or concentration of sites. Displacement with yohimbine and prazosin indicated binding of WB4101 to A-1 receptors. Very young (5 wk) lean (+/.) and obese mice had similar affinity constants (lean 0.13 +/- 0.043 and 34.2 +/- 14.9; obese, 0.12 +/- 0.028 and 20.9 +/- 5.48 nM) and concentrations (lean 22.4 +/- 3.8 and 647 +/- 137; obese, 28.6 +/- 4.6 and 547 +/- 105 fmol/mg protein) of sites. Old (1 yr) mice had high affinity sites similar to those in younger animals (KD lean 0.19 +/- 0.028, obese, 0.25 +/- 0.075; Bmax lean, 60.2 +/- 12.1; obese, 63.1 +/- 13.5 fmol/mg protein). The authors conclude that the ob/ob mouse has normal high affinity A-1 receptors in BAT. Anomalous properties of low affinity binding in old ob/ob mice could not be characterized because of high nonspecific binding. BAT of the ob/ob mouse does not lack A-1 receptors but may have a post-receptor alteration in the A-1 adrenoceptor-mediated response

Cold exposure rapidly induces virtual saturation of brown adipose tissue nuclear T3 receptors

International Nuclear Information System (INIS)

Bianco, A.C.; Silva, J.E.

1988-01-01

Cold exposure induces a rapid increase in uncoupling protein (UCP) concentration in the brown adipose tissue (BAT) of euthyroid, but not hypothyroid, rats. To normalize this response with exogenous 3,5,3'-triiodothyronine (T 3 ), it is necessary to cause systemic hyperthyroidism. In contrast, the same result can be obtained with just replacement doses of thyroxine (T 4 ) and, in euthyroid rats, the normal response of UCP to cold occurs without hyperthyroid plasma T 3 levels. Consequently, the authors explored the possibility that the cold-induced activation of the type II 5'-deiodinase resulted in high levels of nuclear T 3 receptor occupancy in euthyroid rats. Studies were performed with pulse injections of tracer T 3 or T 4 in rats exposed to 4 degree C for different lengths of time (1 h-3 wk). Within 4 h of cold exposure, they observed a significant increase in the nuclear [ 125 I]T 3 derived from the tracer [ 125 I]T 4 injections (T 3 [T 4 ]) and a significant reduction in the nuclear [ 125 I]T 3 derived from [ 125 I]T 3 injections (T 3 [T 3 ]). The number of BAT nuclear T 3 receptors did not increase for up to 3 wk of observation at 4 degree C. The mass of nuclear-bound T 3 was calculated from the nuclear tracer [ 125 I]T 3 [T 3 ] and [ 125 I]T 3 [T 4 ] at equilibrium and the specific activity of serum T 3 and T 4 , respectively. By 4 h after the initiation of the cold exposure, the receptors were >95% occupied and remained so for the 3 weeks of observation. They conclude that the simultaneous activation of the deiodinase with adrenergic BAT stimulation serves the purpose of nearly saturating the nuclear T 3 receptors. This makes possible the realization of the full thermogenic potential of the tissue without causing systemic hyperthyroidism

Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models. Evaluation of insulin and β3-adrenergic receptor agonist effects by 18F-FDG

International Nuclear Information System (INIS)

Ishino, Seigo; Sugita, Taku; Kondo, Yusuke

2017-01-01

One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals. A radiotracer for glucose, 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316, 243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. 18 F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography. In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin

Cellular origins of cold-induced brown adipocytes in adult mice.

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Lee, Yun-Hee; Petkova, Anelia P; Konkar, Anish A; Granneman, James G

2015-01-01

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 increase proliferation in inguinal white adipose tissue (ingWAT), the percentage of BAs, defined as multilocular adipocytes that express uncoupling protein 1, rose from undetectable to 30% of total adipocytes. To trace the origins of cold-induced BAs, we genetically tagged PDGFRα(+) cells and adipocytes prior to cold exposure, using Pdgfra-Cre recombinase estrogen receptor T2 fusion protein (CreER(T2)) and adiponectin-CreER(T2), respectively. In iBAT, cold stress triggered the proliferation and differentiation of PDGFRα(+) cells into BAs. In contrast, all newly observed BAs in ingWAT (5207 out of 5207) were derived from unilocular adipocytes tagged by adiponectin-CreER(T2)-mediated recombination. Surgical denervation of iBAT reduced cold-induced brown adipogenesis by >85%, whereas infusion of norepinephrine (NE) mimicked the effects of cold in warm-adapted mice. NE-induced de novo brown adipogenesis in iBAT was eliminated in mice lacking β1-adrenergic receptors. These observations identify a novel tissue niche for brown adipogenesis in iBAT and further define depot-specific mechanisms of BA recruitment. © FASEB.

Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue

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Diana Vargas

2017-01-01

Full Text Available Adipose tissue can affect the metabolic control of the cardiovascular system, and its anatomic location can affect the vascular function differently. In this study, biochemical and phenotypical characteristics of adipose tissue from periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were obtained from areas surrounding the ascending aorta and sternotomy incision, respectively. Adipose tissues were collected from patients undergoing myocardial revascularization or mitral valve replacement surgery. Morphological studies with hematoxylin/eosin and immunohistochemical assay were performed in situ to quantify adipokine expression. To analyze adipogenic capacity, adipokine expression, and the levels of thermogenic proteins, adipocyte precursor cells were isolated from periaortic and subcutaneous adipose tissues and induced to differentiation. The precursors of adipocytes from the periaortic tissue accumulated less triglycerides than those from the subcutaneous tissue after differentiation and were smaller than those from subcutaneous adipose tissue. The levels of proteins involved in thermogenesis and energy expenditure increased significantly in periaortic adipose tissue. Additionally, the expression levels of adipokines that affect carbohydrate metabolism, such as FGF21, increased significantly in mature adipocytes induced from periaortic adipose tissue. These results demonstrate that precursors of periaortic adipose tissue in humans may affect cardiovascular events and might serve as a target for preventing vascular diseases.

Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene

International Nuclear Information System (INIS)

Miura, Shinji; Tsunoda, Nobuyo; Ikeda, Shinobu; Kai, Yuko; Cooke, David W.; Lane, M. Daniel; Ezaki, Osamu

2004-01-01

Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT

Subcutaneous adipose tissue classification

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A. Sbarbati

2010-11-01

Full Text Available The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT, structural WAT (sWAT and fibrous WAT (fWAT. dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical. In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for

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 ...

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.

Science.gov (United States)

Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Chen, Chan; Chao, Wei; Panagia, Marcello; Sosnovik, David E; Puppala, Dheeraj; Armoundas, Antonis A; Hindle, Allyson; Bloch, Kenneth D; Buys, Emmanuel S; Scherrer-Crosbie, Marielle

2015-07-01

Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thyroid hormones induce browning of white fat

Science.gov (United States)

Martínez-Sánchez, Noelia; Moreno-Navarrete, José M; Contreras, Cristina; Rial-Pensado, Eva; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos

2016-01-01

The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3′,5,5′ tetraiodothyroxyne (T4)-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3′,5-triiodothyronine (T3) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T4. Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance. PMID:27913573

Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

DEFF Research Database (Denmark)

Tobin, L; Simonsen, L; Bülow, J

2010-01-01

The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain......-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P

Endurance training blocks uncoupling protein 1 up-regulation in brown adipose tissue while increasing uncoupling protein 3 in the muscle tissue of rats fed with a high-sugar diet.

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de Queiroz, Karina Barbosa; Rodovalho, Gisele Vieira; Guimarães, Juliana Bohnen; de Lima, Daniel Carvalho; Coimbra, Cândido Celso; Evangelista, Elísio Alberto; Guerra-Sá, Renata

2012-09-01

The mitochondrial uncoupling proteins (UCPs) of interscapular brown adipose tissue (iBAT) and of muscles play important roles in energy balance. For instance, the expression of UCP1 and UCP3 are modulated by free fatty acid gradients induced by high-sugar diets and acute exercise that is dependent on sympathetic stimulation. However, the effects of endurance training in animals fed with high-sugar diets are unknown. This study aims to evaluate the long-term effects of diet and exercise on UCP1 and UCP3 levels and energy balance efficiency. Rats fed with standard or high-sugar (HSD) diets were simultaneously subjected to running training over an 8-week period. After the training period, the rats were decapitated, and the iBAT and gastrocnemius muscle tissues were removed for evaluation of the β₃-receptor, Ucp1, and Ucp3 mRNA and protein expression, which were analyzed by quantitative reverse transcriptase polymerase chain reaction and Western blot, respectively. Groups fed with an HSD displayed a higher adiposity index and iBAT weight (P < .05), whereas exhibited an up-regulation of Ucp1 mRNA and protein levels (P < .05). Training increased β₃-receptor mRNA in iBAT and reduced the Ucp3 mRNA in muscle tissues. In association with an HSD, training restored the increasing β₃-receptor mRNA and greatly up-regulated the levels of Ucp3 mRNA. Therefore, training blocked the HSD-induced up-regulation of UCP1 expression in iBAT, whereas it up-regulated the expression of Ucp3 mRNA in muscle. These results suggest that training enhances the relationship between Ucp1/Ucp3 mRNA levels, which could result in higher energy efficiency, but not when HSD-induced elevated sympathetic activity is maintained. Copyright © 2012. Published by Elsevier Inc.

Brown adipose tissue in young adults who were born preterm or small for gestational age.

Science.gov (United States)

Kistner, Anna; Rydén, Henric; Anderstam, Björn; Hellström, Ann; Skorpil, Mikael

2018-06-27

Brown adipose tissue (BAT) is present and functions to dissipate energy as heat in young adults and can be assessed using magnetic resonance imaging (MRI) to estimate the voxel fat fraction, i.e. proton density fat fraction (PDFF). It is hypothesized that subjects born preterm or small for gestational age (SGA) may exhibit disrupted BAT formation coupled to metabolic factors. Our purpose was to assess the presence of BAT in young adults born extremely preterm or SGA in comparison with controls. We studied 30 healthy subjects (median age, 21 years): 10 born extremely preterm, 10 full term but SGA and 10 full term with a normal birth weight (controls). We utilized an MRI technique combining multiple scans to enable smaller echo spacing and an advanced fat-water separation method applying graph cuts to estimate B0 inhomogeneity. We measured supraclavicular/cervical PDFF, R2*, fat volume, insulin-like growth factor 1, glucagon, thyroid stimulating hormone and the BAT-associated hormones fibroblast growth factor 21 and irisin. The groups did not significantly differ in supraclavicular/cervical PDFF, R2*, fat volume or hormone levels. The mean supraclavicular/cervical PDFF was equivalent between the groups (range 75-77%). Young adults born extremely preterm or SGA show BAT development similar to those born full term at a normal birth weight. Thus, the increased risk of cardiovascular and metabolic disorders in these groups is not due to the absence of BAT, although our results do not exclude possible BAT involvement in this scenario. Larger studies are needed to understand these relationships.

Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

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Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

2010-04-09

Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

Adenovirus 36 DNA in human adipose tissue.

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Ponterio, E; Cangemi, R; Mariani, S; Casella, G; De Cesare, A; Trovato, F M; Garozzo, A; Gnessi, L

2015-12-01

Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.

Neutron organ dose and the influence of adipose tissue

Science.gov (United States)

Simpkins, Robert Wayne

Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

Science.gov (United States)

Nohara, Kazunari; Waraich, Rizwana S; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S; Karsenty, Gérard; Burcelin, Rémy; Mauvais-Jarvis, Franck

2013-06-15

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

The Prevalence and Characteristics of Brown Adipose Tissue in an 18F-FDG PET Study of Koreans

International Nuclear Information System (INIS)

Park, Joon Yeun; Lim, Jung Sub; Park, Eun Young; Cho, A Ra; Kim, Byeong Il; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

2010-01-01

The object of this study was to evaluate the prevalence and characteristics of brown adipose tissue (BAT) in Korean subjects using 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET). Six thousand and five consecutive 18 F-FDG PET/CT scans of 5,115 patients (3,007 females and 2,108 males, mean age 53.5 years) were retrospectively reviewed. We characterized the nature of BAT, such as tis location, and we assessed the influence of sex, age, body mass index (BMI), and temperature on BAT. The prevalence of BAT in Koreans in a single 18 F-FDG PET/CT scan in average conditions was 1.07%. The BAT detection rate was higher in females than males (1.32% vs 0.73%), and also with younger age (7.94% vs 0.73%), and lower BMI (BMI with BAT, 21.1 vs BMI without BAT, 23.15) and cold outdoor temperature (1.65% vs 0.49%). The most frequent location of BAT was the supraclavicular area (left, 0.91%; right, 0.88%) and ventral neck area (left, 0.62%; right, 0.63%). Conclusions The characteristics of BAT in Koreans are not different from those described for Caucasians. However, the low prevalence of BAT in our study might be related to some scan condition like ambient temperature, but further study is needed.

Aging and Adipose Tissue: Potential Interventions for Diabetes and Regenerative Medicine

Science.gov (United States)

Palmer, Allyson K.; Kirkland, James L.

2016-01-01

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies. PMID:26924669

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

BACKGROUND: Brown adipocytes are specialised in dissipating energy through adaptive thermogenesis, whereas white adipocytes are specialised in energy storage. These essentially opposite functions are possible for two reasons relating to mitochondria, namely expression of uncoupling protein 1 (UCP1...... and brown fat, brown adipose tissue fractions and in selected adipose tissues during cold exposure. We find a massive induction of the majority of such genes during brown adipocyte differentiation and recruitment, e.g. of the mitochondrial transcription factors A (Tfam) and B2 (Tfb2m), whereas only a subset...

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit.

Science.gov (United States)

Li, Zhuang; Yi, Chun-Xia; Katiraei, Saeed; Kooijman, Sander; Zhou, Enchen; Chung, Chih Kit; Gao, Yuanqing; van den Heuvel, José K; Meijer, Onno C; Berbée, Jimmy F P; Heijink, Marieke; Giera, Martin; Willems van Dijk, Ko; Groen, Albert K; Rensen, Patrick C N; Wang, Yanan

2017-11-03

Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate. Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice. Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT. Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Contact with existing adipose tissue is inductive for adipogenesis in matrigel.

LENUS (Irish Health Repository)

Kelly, John L

2006-07-01

The effect of adipose tissue on inductive adipogenesis within Matrigel (BD Biosciences) was assessed by using a murine chamber model containing a vascular pedicle. Three-chamber configurations that varied in the access to an adipose tissue source were used, including sealed- and open-chamber groups that had no access and limited access, respectively, to the surrounding adipose tissue, and a sealed-chamber group in which adipose tissue was placed as an autograft. All groups showed neovascularization, but varied in the amount of adipogenesis seen in direct relation to their access to preexisting adipose tissue: open chambers showed strong adipogenesis, whereas the sealed chambers had little or no adipose tissue; adipogenesis was restored in the autograft chamber group that contained 2- to 5-mg fat autografts. These showed significantly more adipogenesis than the sealed chambers with no autograft ( p < 0.01). Autografts with 1mg of fat were capable of producing adipogenesis but did so less consistently than the larger autografts. These findings have important implications for adipose tissue engineering strategies and for understanding de novo production of adipose tissue.

Diet-induced changes in Ucp1 expression in bovine adipose tissues.

Science.gov (United States)

Asano, Hiroki; Yamada, Tomoya; Hashimoto, Osamu; Umemoto, Takenao; Sato, Ryo; Ohwatari, Shiori; Kanamori, Yohei; Terachi, Tomohiro; Funaba, Masayuki; Matsui, Tohru

2013-04-01

Brown adipocytes, which regulate non-shivering thermogenesis, have been believed to exist in a limited number of mammalian species, and only under limited physiological conditions. Recent discoveries indicate that adult humans possess a significant number of functional brown adipocytes. This study explores the regulatory emergence of brown adipocytes in white adipose tissue (WAT) depots of fattening cattle. RT-PCR analyses indicated significant expression of Ucp1, a brown adipocyte-specific gene, in the WAT of 31-month-old Japanese Black steers. Immunohistochemical analysis revealed that Ucp1-positive small adipocytes were dispersed in the subcutaneous WAT. Next, we examined expression level of Ucp1 and other brown adipocyte-selective genes such as Pgc1α, Cidea, Dio2, Cox1, Cox7a1 and Cox8b in WAT of 30-month-old steers fed either diet with low protein/energy content (roughage diet) or that with high protein/energy content (concentrate diet) for 20months. Ucp1 expression in the subcutaneous WAT was significantly higher in the concentrate diet group than in the roughage diet group. Furthermore, the higher Ucp1 expression levels were limited to the subcutaneous WAT, and no differences between groups were detected in the mesenteric, perirenal, intermuscular or intramuscular WAT. Expression of Dio2, Cox1 and Cox8b was higher in the subcutaneous WAT but not in the mesenteric WAT of the concentrate diet group. Furthermore, expression of Prdm16, a positive regulator of differentiation toward brown adipocyte-lineage cells, and expression of leptin, a molecule that enhances activity of brown adipocytes, were significantly higher in the subcutaneous WAT of the concentrate diet group. This study demonstrates the presence of brown adipocytes in WAT depots of fattening cattle, and suggests the diet-related modulation of expression of genes predominantly expressed in brown adipocytes. Copyright © 2013 Elsevier Inc. All rights reserved.

Non-invasive Assessments of Adipose Tissue Metabolism In Vitro.

Science.gov (United States)

Abbott, Rosalyn D; Borowsky, Francis E; Quinn, Kyle P; Bernstein, David L; Georgakoudi, Irene; Kaplan, David L

2016-03-01

Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with non-invasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored.

Growth hormone and adipose tissue: beyond the adipocyte.

Science.gov (United States)

Berryman, Darlene E; List, Edward O; Sackmann-Sala, Lucila; Lubbers, Ellen; Munn, Rachel; Kopchick, John J

2011-06-01

The last two decades have seen resurgence in research focused on adipose tissue. In part, the enhanced interest stems from an alarming increase in obesity rates worldwide. However, an understanding that this once simple tissue is significantly more intricate and interactive than previously realized has fostered additional attention. While few would argue that growth hormone (GH) radically alters fat mass, newer findings revealing the complexity of adipose tissue requires that GH's influence on this tissue be reexamined. Therefore, the objective of this review is to describe the more recent understanding of adipose tissue and to summarize our current knowledge of how GH may influence and contribute to these newer complexities of this tissue with special focus on the available data from mice with altered GH action. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome.

Science.gov (United States)

Madani, Zohra; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J; Ait Yahia, Dalila

2012-02-01

The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective

Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

DEFF Research Database (Denmark)

Sun, Kai; Park, Jiyoung; Gupta, Olga T

2014-01-01

to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the 'unhealthy' adipose tissue milieu, triggering...

Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

Directory of Open Access Journals (Sweden)

Liyuan Chen

2018-03-01

Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Andrew A. Bremer

2013-01-01

Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

Adipose tissue macrophages: going off track during obesity

NARCIS (Netherlands)

Boutens, L.; Stienstra, R.

2016-01-01

Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

Does bariatric surgery improve adipose tissue function?

Science.gov (United States)

Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

2017-01-01

Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

Automatic Segmentation of Abdominal Adipose Tissue in MRI

DEFF Research Database (Denmark)

Mosbech, Thomas Hammershaimb; Pilgaard, Kasper; Vaag, Allan

2011-01-01

of intensity in-homogeneities. This effect is estimated by a thin plate spline extended to fit two classes of automatically sampled intensity points in 3D. Adipose tissue pixels are labelled with fuzzy c-means clustering and locally determined thresholds. The visceral and subcutaneous adipose tissue...

Food restriction attenuates oxidative stress in brown adipose tissue of striped hamsters acclimated to a warm temperature.

Science.gov (United States)

Zhang, Ji-Ying; Zhao, Xiao-Ya; Wang, Gui-Ying; Wang, Chun-Ming; Zhao, Zhi-Jun

2016-05-01

It has been suggested that the up-regulation of uncoupling proteins (UCPs) decreases reactive oxygen species (ROS) production, in which case there should be a negative relationship between UCPs expression and ROS levels. In this study, the effects of temperature and food restriction on ROS levels and metabolic rate, UCP1 mRNA expression and antioxidant levels were examined in the brown adipose tissue (BAT) of the striped hamsters (Cricetulus barabensis). The metabolic rate and food intake of hamsters which had been restricted to 80% of ad libitum food intake, and acclimated to a warm temperature (30°C), decreased significantly compared to a control group. Hydrogen peroxide (H2O2) levels were 42.9% lower in food restricted hamsters than in the control. Malonadialdehyde (MDA) levels of hamsters acclimated to 30°C that were fed ad libitum were significantly higher than those of the control group, but 60.1% lower than hamsters that had been acclimated to the same temperature but subject to food restriction. There were significantly positive correlations between H2O2 and, MDA levels, catalase activity, and total antioxidant capacity. Cytochrome c oxidase activity and UCP1 mRNA expression significantly decreased in food restricted hamsters compared to the control. These results suggest that warmer temperatures increase oxidative stress in BAT by causing the down-regulation of UCP1 expression and decreased antioxidant activity, but food restriction may attenuate the effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation secondary to catecholamine-secreting pheochromocytoma?

Science.gov (United States)

Joshi, Prathamesh Vijay; Lele, Vikram Ramchandra

2012-05-01

Fused positron emission tomography-computed tomography (PET/CT) technology has enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential source of false-positive interpretations for PET. The typical locations of BAT include neck, supraclavicular area, mediastinum, and paravertebral intercostal spaces. Examples of atypical locations for BAT include posterior neck, left paratracheal area, axillae, perirenal area, and retrocrural area. We report PET/CT findings in a young male patient with malignant retroperitoneal extra-adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple locations including mesenteric BAT. We also propose catecholamine-secreting pheochromocytoma as a possible cause of BAT activation in our case.

Milk Fat Globule Membrane Attenuates High-Fat Diet-Induced Obesity by Inhibiting Adipogenesis and Increasing Uncoupling Protein 1 Expression in White Adipose Tissue of Mice

Directory of Open Access Journals (Sweden)

Tiange Li

2018-03-01

Full Text Available Milk fat globule membrane (MFGM, a protein-lipid complex surrounding the fat globules in milk, has many health benefits. The aim of the current study was to investigate whether MFGM could prevent obesity through inhibiting adipogenesis and promoting brown remodeling of white adipose tissue (WAT in mice fed with high-fat diet. C57BL/6 mice were fed a normal diet (ND, high-fat diet (HFD, HFD plus MFGM at 100 mg/kg BW, 200 mg/kg BW or 400 mg/kg BW for 8 weeks. Results showed that MFGM suppressed body weight gain induced by HFD, reduced white adipose tissue (WAT mass accompanied with the decrease in adipocyte sizes. MFGM was found to have partially improved serum lipid profiles, as well as to have suppressed HFD-induced adipogenesis as shown by reduced expression of peroxisome proliferators-activator receptor-γ (PPARγ, CCAAT/enhancer-binding protein-α (C/EBPα and sterol regulatory element-binding protein-1c (SREBP-1c. MFGM also markedly increased the phosphorylation of AMP-activated protein kinase (AMPK and acetyl-CoA carboxylase (ACC, showing activation of AMPK pathway. Moreover, MFGM promoted browning of inguinal WAT by upregulation the protein expression of uncoupling protein 1 (UCP1 in HFD mice. Taken together, these findings provide evidence that MFGM may protect against diet-induced adiposity by suppressing adipogenesis and promoting brown-like transformation in WAT.

Divergent responses to thermogenic stimuli in BAT and subcutaneous adipose tissue from interleukin 18 and interleukin 18 receptor 1-deficient mice.

Science.gov (United States)

Pazos, Patricia; Lima, Luis; Tovar, Sulay; González-Touceda, David; Diéguez, Carlos; García, María C

2015-12-10

Brown and beige adipocytes recruitment in brown (BAT) or white adipose tissue, mainly in the inguinal fat pad (iWAT), meet the need for temperature adaptation in cold-exposure conditions and protect against obesity in face of hypercaloric diets. Using interleukin18 (Il18) and Il18 receptor 1- knockout (Il18r1-KO) mice, this study aimed to investigate the role of IL18 signaling in BAT and iWAT activation and thermogenesis under both stimuli. Il18-KO, extremely dietary obesity-prone as previously described, failed to develop diet-induced thermogenesis as assessed by BAT and iWAT Ucp1 mRNA levels. Overweight when fed standard chow but not HFD, HFD-fed Il18r1-KO mice exhibited increased iWAT Ucp1 gene expression. Energy expenditure was reduced in pre-obese Il18r1-KO mice and restored upon HFD-challenge. Cold exposure lead to similar results; Il18r1-KO mice were protected against acute body temperature drop, displaying a more brown-like structure, alternative macrophage activation and thermogenic gene expression in iWAT than WT controls. Opposite effects were observed in Il18-KO mice. Thus, Il18 and Il18r1 genetic ablation disparate effects on energy homeostasis are likely mediated by divergent BAT responses to thermogenic stimuli as well as iWAT browning. These results suggest that a more complex receptor-signaling system mediates the IL18 adipose-tissue specific effects in energy expenditure.

Brown Adipose Tissue Can Be Activated or Inhibited within an Hour before 18F-FDG Injection: A Preliminary Study with MicroPET

Directory of Open Access Journals (Sweden)

Chenxi Wu

2011-01-01

Full Text Available Brown adipose tissue (BAT is emerging as a potential target for treating human obesity. It has been indicated that BAT is rich in innervations of sympathetic nerve control. Using 18F-FDG microPET imaging, this study aims at evaluating how factors related to sympathetic activation/inhibition changed BAT metabolism of mice. BAT 18F-FDG uptake were semiquantitatively evaluated in different groups of mice under temperature (cold or warm stimulus or pharmacological interventions (norepinephrine, epinephrine, isoprenaline, or propranolol and were compared with the corresponding controls. It was found that BAT activation can be stimulated by cold exposure (P=1.96×10−4, norepinephrine (P=.002, or both (P=2.19×10−6 within an hour before 18F-FDG injection and can also be alleviated by warming up (P=.001 or propranolol lavage (P=.027. This preliminary study indicated that BAT function could be evaluated by 18F-FDG PET imaging through short-term interventions, which paved the way for further investigation of the relationship between human obesity and BAT dysfunction.

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

Science.gov (United States)

LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

2016-02-01

The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

Human adipose-derived stem cells: definition, isolation, tissue-engineering applications.

Science.gov (United States)

Nae, S; Bordeianu, I; Stăncioiu, A T; Antohi, N

2013-01-01

Recent researches have demonstrated that the most effective repair system of the body is represented by stem cells - unspecialized cells, capable of self-renewal through successive mitoses, which have also the ability to transform into different cell types through differentiation. The discovery of adult stem cells represented an important step in regenerative medicine because they no longer raises ethical or legal issues and are more accessible. Only in 2002, stem cells isolated from adipose tissue were described as multipotent stem cells. Adipose tissue stem cells benefits in tissue engineering and regenerative medicine are numerous. Development of adipose tissue engineering techniques offers a great potential in surpassing the existing limits faced by the classical approaches used in plastic and reconstructive surgery. Adipose tissue engineering clinical applications are wide and varied, including reconstructive, corrective and cosmetic procedures. Nowadays, adipose tissue engineering is a fast developing field, both in terms of fundamental researches and medical applications, addressing issues related to current clinical pathology or trauma management of soft tissue injuries in different body locations.

Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty.

Science.gov (United States)

Stout, Michael B; Justice, Jamie N; Nicklas, Barbara J; Kirkland, James L

2017-01-01

Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation

Science.gov (United States)

Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J.; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) γ agonist. Hence, we hypothesized that F4/80hi and F4/80lo ATM differentially express PPAR γ. This study phenotypically and functionally characterizes F4/80hi and F4/80lo ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80lo and F4/80hi ATM by quantitative real-time RT-PCR. We show that while F4/80lo macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80lo and F4/80hi ATM. Moreover, accumulation of F4/80hi ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80hi ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-α, MCP-1, and IL-10 than F4/80lo ATM. Gene expression analyses of the sorted populations revealed that only the F4/80lo population produced IL-4, whereas the F4/80hi ATM expressed greater amounts of PPAR γ, δ, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR γ in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR γ is differentially expressed in F4/80hi versus F4/80low ATM subsets and its deficiency favors a predominance of M1 markers in WAT. PMID:19423085

PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation.

Science.gov (United States)

Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT.

Effects of 3,5-diiodo-L-thyronine on browning of white adipose tissue%3,5-二碘-L-甲状腺素对白色脂肪棕色化的作用

Institute of Scientific and Technical Information of China (English)

柯孟婷; 孙家忠; 李扬

2016-01-01

目的 探究3,5-二碘-L-甲状腺素(T2)诱导白色脂肪棕色化的作用.方法 3T3-LI脂肪前体细胞诱导分化并用油红O染色进行鉴定;细胞分化过程中予不同浓度梯度(1 nmol/L、10 nmol/L、100 nmol/L)的T2处理,待细胞分化成熟后,分别用实时荧光定量PCR、Western印迹检测解耦联蛋白-1(UCP-1)表达水平的变化;仅予高浓度(100 nmol/L) T2处理,Western印迹法检测其他棕色脂肪功能性基因,包括诱导细胞死亡DNA片段化因子α样效应因子A(CIDEA)、过氧化物酶体增殖物活化受体γ协同刺激因子-1α(PGC-1α)蛋白表达变化.结果 3T3-L1脂肪前体细胞呈成纤维细胞样形态,胞浆中无脂滴;诱导分化成熟后光镜下油红O染色可见细胞内大量环状脂滴.在细胞分化过程中予不同浓度T2干预后,分化成熟的脂肪细胞上UCP-1 mRNA水平均有升高(t=3.97、11.77、17.7,P均＜0.05),蛋白表达水平也均有改变(t=13.31、14.55、23.62,P均＜0.05),且在高浓度(100nmoL/L)下最明显.在高浓度T2(100 nmol/L)干预下,成熟脂肪细胞的棕色脂肪其他功能性基因蛋白CIDEA、PGC-1α水平表达增加(t=15.92、17.36,P均＜0.05).结论 T2可诱导由3T3-L1脂肪前体细胞分化而来的成熟白色脂肪细胞表达棕色脂肪功能性基因.%Objective To explore the effects of 3,5-diiodo-L-thyronine(T2) on browning of white adipose tissue.Methods Differentiation of 3T3-L1 adipose precursor cells were induced and identified by oil red O staining.During the differentiation process,3T3-L1 were treated by different concentrations of T2 (1 nmol/L,10 nmol/L,100 nmol/L).After the maturation of 3T3-L1,the level of uncoupling protein-1 (UCP-1) mRNA and protein were detected by RT-PCR and Western blotting,respectively.Specific proteins of brown adipose tissue including cell death-inducing DNA fragmentation factor alpha like effector A (CIDEA) and peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1 α) were

Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance

DEFF Research Database (Denmark)

Grünberg, John R; Hoffmann, Jenny M; Hedjazifar, Shahram

2017-01-01

remained insulin sensitive, had increased glucose uptake by adipose cells and skeletal muscle in vivo and ex vivo, increased GLUT4, increased ChREBP and markers of adipose tissue lipogenesis. Serum levels of the novel fatty acid esters of hydroxy fatty acids (FAHFAs) were increased and transplantation...

Adipose tissue and skeletal muscle blood flow during mental stress

Energy Technology Data Exchange (ETDEWEB)

Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

1989-01-01

Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

Adipose tissue and skeletal muscle blood flow during mental stress

International Nuclear Information System (INIS)

Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

1989-01-01

Mental stress [a modified Stroop color word conflict test (CWT)] increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation

Gene Expression Signature in Adipose Tissue of Acromegaly Patients

Science.gov (United States)

Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

2015-01-01

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

miRNAs in Human Subcutaneous Adipose Tissue

DEFF Research Database (Denmark)

Kristensen, Malene M.; Davidsen, Peter K.; Vigelso, Andreas

2017-01-01

Objective Obesity is central in the development of insulin resistance. However, the underlying mechanisms still need elucidation. Dysregulated microRNAs (miRNAs; post-transcriptional regulators) in adipose tissue may present an important link. Methods The miRNA expression in subcutaneous adipose ...

Insulin action in adipose tissue and muscle in hypothyroidism.

Science.gov (United States)

Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia; Boutati, Eleni; Maratou, Eirini; Panagiotakos, Demosthenes B; Koukkou, Efi; Tzanela, Marinela; Thalassinos, Nikos; Raptis, Sotirios A

2006-12-01

Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited. To investigate this, a meal was given to 11 hypothyroid (HO; aged 45 +/- 3 yr) and 10 euthyroid subjects (EU; aged 42 +/- 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V)glucose(BF), lipoprotein lipase as (A-V)Triglycerides(BF), and lipolysis as [(V-A)glycerol(BF)]-lipoprotein lipase. The HO group had higher glucose and insulin levels than the EU group (P hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.

Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation.

Science.gov (United States)

Titos, Esther; Clària, Joan

2013-12-01

Chronic low-grade inflammation in adipose tissue has been recognized as a key step in the development of obesity-associated complications. In obesity, the accumulation of infiltrating macrophages in adipose tissue and their phenotypic switch to M1-type dysregulate inflammatory adipokine production leading to obesity-linked insulin resistance. Resolvins are potent anti-inflammatory and pro-resolving mediators endogenously generated from omega-3 fatty acids that act as "stop-signals" of the inflammatory response promoting the resolution of inflammation. Recently, a deficit in the production of these endogenous anti-inflammatory signals has been demonstrated in obese adipose tissue. The restoration of their levels by either exogenous administration of these mediators or feeding omega-3-enriched diets, improves the inflammatory status of adipose tissue and ameliorates metabolic dysfunction. Here, we review the current knowledge on the role of these endogenous autacoids in the resolution of adipose tissue inflammation with special emphasis on their functional actions on macrophages. Copyright © 2013 Elsevier Inc. All rights reserved.

Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks.

NARCIS (Netherlands)

De Goede, P.; Sen, Satish; Oosterman, Johanneke E; Kalsbeek, A.

2018-01-01

The effects of feeding behavior and diet composition,as well as their possible interactions,on daily (clock) gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue(WAT), but hardly in other metabolic tissues such as skeletal muscle (SM) and

Evidence for the ectopic synthesis of melanin in human adipose tissue.

Science.gov (United States)

Randhawa, Manpreet; Huff, Tom; Valencia, Julio C; Younossi, Zobair; Chandhoke, Vikas; Hearing, Vincent J; Baranova, Ancha

2009-03-01

Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes, in retinal pigment epithelium (RPE) cells, in the inner ear, and in the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes. In the current study, we confirmed the expression of melanogenesis-related mRNAs and proteins in human adipose tissue using real-time polymerase chain reaction and immunohistochemical staining. TYR mRNA signals were also detected by in situ hybridization in visceral adipocytes. The presence of melanin in human adipose tissue was revealed both by Fontana-Masson staining and by permanganate degradation of melanin coupled with liquid chromatography/ultraviolet/mass spectrometry determination of the pyrrole-2,3,5-tricarboxylic acid (PTCA) derivative of melanin. We also compared melanogenic activities in adipose tissues and in other human tissues using the L-[U-(14)C] tyrosine assay. A marked heterogeneity in the melanogenic activities of individual adipose tissue extracts was noted. We hypothesize that the ectopic synthesis of melanin in obese adipose may serve as a compensatory mechanism that uses its anti-inflammatory and its oxidative damage-absorbing properties. In conclusion, our study demonstrates for the first time that the melanin biosynthesis pathway is functional in adipose tissue.

Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat

Directory of Open Access Journals (Sweden)

Lu Yao

2017-07-01

Full Text Available Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a β-adrenergic agonist. Deletion of SIRT6 in adipose tissue impairs the thermogenic function of brown adipocytes, causing a morphological “whitening” of brown fat, reduced oxygen (O2 consumption, obesity, decreased core body temperature, and cold sensitivity. Fat SIRT6-deleted mice exhibit increased blood glucose levels, severe insulin resistance, and hepatic steatosis. Moreover, SIRT6 deficiency inhibits the browning of white adipose tissue (WAT following cold exposure or β3-agonist treatment. Depletion of SIRT6 expression in brown adipocytes reduces expression of thermogenic genes, causing a reduction in cellular respiration. Conversely, SIRT6 overexpression in primary fat cells stimulates the thermogenic program. Mechanistically, SIRT6 interacts with and promotes phospho-ATF2 binding to the PGC-1α gene promoter to activate its expression. The present study reveals a critical role for SIRT6 in regulating thermogenesis of fat.

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: ALL.Adp.10.AllAg.Adipose_Tissue [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Adp.10.AllAg.Adipose_Tissue hg19 All antigens Adipocyte Adipose Tissue SRX13473...2 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Adp.10.AllAg.Adipose_Tissue.bed ...

File list: ALL.Adp.05.AllAg.Adipose_Tissue [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Adp.05.AllAg.Adipose_Tissue hg19 All antigens Adipocyte Adipose Tissue SRX13473...2 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Adp.05.AllAg.Adipose_Tissue.bed ...

Protein Kinase A Regulatory Subunits in Human Adipose Tissue

Science.gov (United States)

Mantovani, Giovanna; Bondioni, Sara; Alberti, Luisella; Gilardini, Luisa; Invitti, Cecilia; Corbetta, Sabrina; Zappa, Marco A.; Ferrero, Stefano; Lania, Andrea G.; Bosari, Silvano; Beck-Peccoz, Paolo; Spada, Anna

2009-01-01

OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS—The expression of the different PKA regulatory subunits was evaluated by immunohistochemistry, Western blot, and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS—Expression techniques showed that R2B was the most abundant regulatory protein, both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly lower in both subcutaneous and visceral adipose tissues from obese than nonobese patients and negatively correlated with BMI, waist circumference, insulin levels, and homeostasis model assessment of insulin resistance. Moreover, both basal and stimulated PKA activity and glycerol release were significantly lower in visceral adipose tissue from obese patients then nonobese subjects. CONCLUSIONS—Our results first indicate that, in human adipose tissue, there are important BMI-related differences in R2B expression and PKA activation, which might be included among the multiple determinants involved in the different lipolytic response to β-adrenergic activation in obesity. PMID:19095761

A Low-Protein, High-Carbohydrate Diet Stimulates Thermogenesis in the Brown Adipose Tissue of Rats via ATF-2.

Science.gov (United States)

de França, Suélem A; dos Santos, Maísa P; Przygodda, Franciele; Garófalo, Maria Antonieta R; Kettelhut, Isis C; Magalhães, Diego A; Bezerra, Kalinne S; Colodel, Edson M; Flouris, Andreas D; Andrade, Cláudia M B; Kawashita, Nair H

2016-03-01

The aim of this study was to evaluate thermogenesis in the interscapular brown adipose tissue (IBAT) of rats submitted to low-protein, high-carbohydrate (LPHC) diet and the involvement of adrenergic stimulation in this process. Male rats (~100 g) were submitted to LPHC (6%-protein; 74%-carbohydrate) or control (C; 17%-protein; 63%-carbohydrate) isocaloric diets for 15 days. The IBAT temperature was evaluated in the rats before and after the administration of noradrenaline (NA) (20 µg 100 g b w(-1) min(-1)). The expression levels of uncoupling protein 1 (UCP1) and other proteins involved in the regulation of UCP1 expression were determined by Western blot (Student's t test, P ≤ 0.05). The LPHC diet promoted a 1.1 °C increase in the basal temperature of IBAT when compared with the basal temperature in the IBAT of the C group. NA administration promoted a 0.3 °C increase in basal temperature in the IBAT of the C rats and a 0.5 °C increase in the IBAT of the LPHC group. The level of UCP1 increased 60% in the IBAT of LPHC-fed rats, and among the proteins involved in its expression, such as β3-AR and α1-AR, there was a 40% increase in the levels of p38-MAPK and a 30% decrease in CREB when compared to the C rats. The higher sympathetic flux to IBAT, which is a consequence of the administration of the LPHC diet to rats, activates thermogenesis and increases the expression of UCP1 in the tissue. Our results suggest that the increase in UCP1 content may occur via p38 MAPK and ATF2.

Critical illness induces alternative activation of M2 macrophages in adipose tissue.

Science.gov (United States)

Langouche, Lies; Marques, Mirna B; Ingels, Catherine; Gunst, Jan; Derde, Sarah; Vander Perre, Sarah; D'Hoore, André; Van den Berghe, Greet

2011-01-01

We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels. Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

Science.gov (United States)

Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

2013-01-01

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

Epicardial adipose tissue in endocrine and metabolic diseases.

Science.gov (United States)

Iacobellis, Gianluca

2014-05-01

Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

Epicardial Adipose Tissue Thickness in Patients With Subclinical Hypothyroidism and the Relationship Thereof With Visceral Adipose Tissue Thickness.

Science.gov (United States)

Arpaci, Dilek; Gurkan Tocoglu, Aysel; Yilmaz, Sabiye; Korkmaz, Sumeyye; Ergenc, Hasan; Gunduz, Huseyin; Keser, Nurgul; Tamer, Ali

2016-03-01

Subclinical hypothyroidism (SH) is associated with cardiovascular metabolic syndromes, especially dislipidemia and abdominal obesity. Visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) have the same ontogenic origin and produce many proinflammatory and proatherogenic cytokines. We evaluated EAT and VAAT thickness in patients with SH. Forty-one patients with SH and 35 controls were included in the study. Demographical and anthropometric features of both patients and controls were recorded. Thyroid and metabolic parameters were measured. EAT was measured using 2D-transthoracic echocardiography. The age and gender distributions were similar in the two groups (P = 0.998 and P = 0.121, respectively). Body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC), the WC/HC ratio, and the thicknesses of VAAT and abdominal subcutaneous adipose tissue were higher in the case group than the control group (all P values 0.05). We found no difference between the two groups in fasting plasma glucose (FPG) level (P = 0.780), but the levels of LDL-C and TG differed significantly (P = 0.002 and P = 0.026, respectively). The serum TSH level was higher and the FT4 level was lower in the case than the control group (both P values <0.01). Increased abdominal adipose tissue thickness in patients with SH is associated with atherosclerosis. To detemine the risk of atherosclerosis in such patients, EAT measurements are valuable; such assessment is simple to perform.

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering.

Science.gov (United States)

Qi, Dianjun; Wu, Shaohua; Kuss, Mitchell A; Shi, Wen; Chung, Soonkyu; Deegan, Paul T; Kamenskiy, Alexey; He, Yini; Duan, Bin

2018-05-26

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and the addition of PEG-4A improved the robustness and mechanical properties. The cryogels supported human adipose progenitor cell (HWA) and adipose derived mesenchymal stromal cell adhesion, proliferation, and adipogenic differentiation and maturation, regardless of the addition of PEG-4A. The HWA laden cryogels facilitated the co-culture of human umbilical vein endothelial cells (HUVEC) and capillary-like network formation, which in return also promoted adipogenesis. We further combined cryogels with 3D bioprinting to generate handleable adipose constructs with clinically relevant size. 3D bioprinting enabled the deposition of multiple bioinks onto the cryogels. The bioprinted flap-like constructs had an integrated structure without delamination and supported vascularization. Adipose tissue engineering is promising for reconstruction of soft tissue defects, and also challenging for restoring and maintaining soft tissue volume and shape, and achieving vascularization and integration. In this study, we fabricated cryogels with mechanical robustness, injectability, and stretchability by using cryopolymerization. The cryogels promoted cell adhesion, proliferation, and adipogenic

Maternal nutritional manipulations program adipose tissue dysfunction in offspring

Directory of Open Access Journals (Sweden)

Simon eLecoutre

2015-05-01

Full Text Available Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates. Maternal nutritional manipulations reprogram offspring’s adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations.

CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

NARCIS (Netherlands)

Park, Jong-Gil; Xu, Xu; Cho, Sungyun; Hur, Kyu Yeon; Lee, Myung-Shik; Kersten, Sander; Lee, Ann-Hwee

2016-01-01

Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG

Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*

OpenAIRE

Herman, Mark A.; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

2010-01-01

Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent obse...

Adipose tissue transcriptome changes during obesity development in female dogs.

Science.gov (United States)

Grant, Ryan W; Vester Boler, Brittany M; Ridge, Tonya K; Graves, Thomas K; Swanson, Kelly S

2011-03-29

During the development of obesity, adipose tissue undergoes major expansion and remodeling, but the biological processes involved in this transition are not well understood. The objective of this study was to analyze global gene expression profiles of adipose tissue in dogs, fed a high-fat diet, during the transition from a lean to obese phenotype. Nine female beagles (4.09 ± 0.64 yr; 8.48 ± 0.35 kg) were randomized to ad libitum feeding or body weight maintenance. Subcutaneous adipose tissue biopsy, blood, and dual x-ray absorptiometry measurements were collected at 0, 4, 8, 12, and 24 wk of feeding. Serum was analyzed for glucose, insulin, fructosamine, triglycerides, free fatty acids, adiponectin, and leptin. Formalin-fixed adipose tissue was used for determination of adipocyte size. Adipose RNA samples were hybridized to Affymetrix Canine 2.0 microarrays. Statistical analysis, using repeated-measures ANOVA, showed ad libitum feeding increased (P obesity development.

Generating an Engineered Adipose Tissue Flap Using an External Suspension Device.

Science.gov (United States)

Wan, Jinlin; Dong, Ziqing; Lei, Chen; Lu, Feng

2016-07-01

The tissue-engineering chamber technique can generate large volumes of adipose tissue, which provides a potential solution for the complex reconstruction of large soft-tissue defects. However, major drawbacks of this technique are the foreign-body reaction and the volume limitation imposed by the chamber. In this study, the authors developed a novel tissue-engineering method using a specially designed external suspension device that generates an optimized volume of adipose flap and avoids the implantation of foreign material. The rabbits were processed using two different tissue-engineering methods, the external suspension device technique and the traditional tissue-engineering chamber technique. The adipose flaps generated by the external suspension device had a normal adipose tissue structure that was as good as that generated by the traditional tissue-engineering chamber, but the flap volume was much larger. The final volume of the engineered adipose flap grew between weeks 0 and 36 from 5.1 ml to 30.7 ml in the traditional tissue-engineering chamber group and to 80.5 ml in the external suspension device group. During the generation process, there were no marked differences between the two methods in terms of structural and cellular changes of the flap, except that the flaps in the traditional tissue-engineering chamber group had a thicker capsule at the early stage. In addition, the enlarged flaps generated by the external suspension device could be reshaped into specific shapes by the implant chamber. This minimally invasive external suspension device technique can generate large-volume adipose flaps. Combined with a reshaping method, this technique should facilitate clinical application of adipose tissue engineering.

Impact of Growth Hormone on Regulation of Adipose Tissue.

Science.gov (United States)

Troike, Katie M; Henry, Brooke E; Jensen, Elizabeth A; Young, Jonathan A; List, Edward O; Kopchick, John J; Berryman, Darlene E

2017-06-18

Increasing prevalence of obesity and obesity-related conditions worldwide has necessitated a more thorough understanding of adipose tissue (AT) and expanded the scope of research in this field. AT is now understood to be far more complex and dynamic than previously thought, which has also fueled research to reevaluate how hormones, such as growth hormone (GH), alter the tissue. In this review, we will introduce properties of AT important for understanding how GH alters the tissue, such as anatomical location of depots and adipokine output. We will provide an overview of GH structure and function and define several human conditions and cognate mouse lines with extremes in GH action that have helped shape our understanding of GH and AT. A detailed discussion of the GH/AT relationship will be included that addresses adipokine production, immune cell populations, lipid metabolism, senescence, differentiation, and fibrosis, as well as brown AT and beiging of white AT. A brief overview of how GH levels are altered in an obese state, and the efficacy of GH as a therapeutic option to manage obesity will be given. As we will reveal, the effects of GH on AT are numerous, dynamic and depot-dependent. © 2017 American Physiological Society. Compr Physiol 7:819-840, 2017. Copyright © 2017 John Wiley & Sons, Inc.

Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis.

Science.gov (United States)

Sidossis, Labros; Kajimura, Shingo

2015-02-01

Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, plays an important role in the regulation of energy balance. Two types of thermogenic adipocytes with distinct developmental and anatomical features exist in rodents and humans: classical brown adipocytes and beige (also referred to as brite) adipocytes. While classical brown adipocytes are located mainly in dedicated BAT depots of rodents and infants, beige adipocytes sporadically reside with white adipocytes and emerge in response to certain environmental cues, such as chronic cold exposure, a process often referred to as "browning" of white adipose tissue. Recent studies indicate the existence of beige adipocytes in adult humans, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, including type 2 diabetes. This Review aims to cover recent progress in our understanding of the anatomical, developmental, and functional characteristics of brown and beige adipocytes and discuss emerging questions, with a special emphasis on adult human BAT.

Regular aerobic exercise correlates with reduced anxiety and incresed levels of irisin in brain and white adipose tissue.

Science.gov (United States)

Uysal, Nazan; Yuksel, Oguz; Kizildag, Servet; Yuce, Zeynep; Gumus, Hikmet; Karakilic, Aslı; Guvendi, Guven; Koc, Basar; Kandis, Sevim; Ates, Mehmet

2018-05-29

We have recently shown that regular voluntary aerobic exercised rats have low levels of anxiety. Irisin is an exercise-induced myokine that is produced by many tissues; and the role it plays in anxiolytic behavior is unknown. In this study we aimed to investigate the correlation between anxiety like behavior and irisin levels following regular voluntary aerobic exercise in male mice. We've have shown that anxiety levels decreased in exercised mice, while irisin levels increased in the brain, brown adipose tissue, white adipose tissue, kidney, and pancreas tissues. No significant difference of irisin levels in the liver, muscle and serum were detected in the exercise group, when compared to controls. In addition, there was a strong positive correlation between brain irisin levels and activity in middle area of open field test and in the open arms of elevated plus maze test; both which are indicators of low anxiety levels. Our results suggest that decrease in anxiolytic behavior due to regular voluntary exercise may be associated with locally produced brain irisin. White adipose tissue irisin levels also correlated very strongly with low anxiety. However, no serum irisin increase was detected, ruling out the possibility of increased peripheral irisin levels affecting the brain via the bloodstream. Further research is necessary to explain the mechanisms of which peripheral and central irisin effects anxiety and the brain region affected. Copyright © 2018 Elsevier B.V. All rights reserved.

Prolactin suppresses malonyl-CoA concentration in human adipose tissue

DEFF Research Database (Denmark)

Nilsson, L. A.; Roepstorff, Carsten; Kiens, Bente

2009-01-01

Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however......, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77......+/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue...

Responses of the insulin signaling pathways in the brown adipose tissue of rats following cold exposure.

Science.gov (United States)

Wang, Xiaofei; Wahl, Richard

2014-01-01

The insulin signaling pathway is critical for the control of blood glucose levels. Brown adipose tissue (BAT) has also been implicated as important in glucose homeostasis. The effect of short-term cold exposure on this pathway in BAT has not been explored. We evaluated the effect of 4 hours of cold exposure on the insulin pathway in the BAT of rats. Whole genomic microarray chips were used to examine the transcripts of the pathway in BAT of rats exposed to 4°C and 22°C for 4 hours. The 4 most significantly altered pathways following 4 hours of cold exposure were the insulin signaling pathway, protein kinase A, PI3K/AKT and ERK/MAPK signaling. The insulin signaling pathway was the most affected. In the documented 142 genes of the insulin pathway, 42 transcripts (29.6%) responded significantly to this cold exposure with the least false discovery rate (Benjamini-Hochberg Multiple Testing: -log10 (p-value)  = 7.18). Twenty-seven genes (64%) were up-regulated, including the insulin receptor (Insr), insulin substrates 1 and 2 (Irs1 and Irs2). Fifteen transcripts (36%) were down-regulated. Multiple transcripts of the primary target and secondary effector targets for the insulin signaling were also up-regulated, including those for carbohydrate metabolism. Using western blotting, we demonstrated that the cold induced higher Irs2, Irs1, and Akt-p protein levels in the BAT than in the BAT of controls maintained at room temperature, and higher Akt-p protein level in the muscle. this study demonstrated that 4 hours of cold exposure stimulated the insulin signaling pathway in the BAT and muscle of overnight fasted rats. This raises the possibility that acute cold stimulation may have potential to improve glucose clearance and insulin sensitivity.

Polychlorinated naphthalenes in human adipose tissue from New York, USA

International Nuclear Information System (INIS)

Kunisue, Tatsuya; Johnson-Restrepo, Boris; Hilker, David R.; Aldous, Kenneth M.; Kannan, Kurunthachalam

2009-01-01

Polychlorinated naphthalenes (PCNs) are persistent, bioaccumulative, and toxic contaminants. Prior to this study, the occurrence of PCNs in human adipose tissues from the USA has not been analyzed. Here, we have measured concentrations of PCNs in human adipose tissue samples collected in New York City during 2003-2005. Concentrations of PCNs were in the range of 61-2500 pg/g lipid wt. in males and 21-910 pg/g lipid wt. in females. PCN congeners 52/60 (1,2,3,5,7/1,2,4,6,7) and 66/67 (1,2,3,4,6,7/1,2,3,5,6,7) were predominant, collectively accounting for 66% of the total PCN concentrations. Concentrations of PCNs in human adipose tissues were 2-3 orders of magnitude lower than the previously reported concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Concentrations of PCNs were not correlated with PCB concentrations. The contribution of PCNs to dioxin-like toxic equivalents (TEQs) in human adipose tissues was estimated to be <1% of the polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F)-TEQs. - Polychlorinated naphthalenes have been measured in human adipose tissues from the USA for the first time

Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue

NARCIS (Netherlands)

Gallagher, D.; Kuznia, P.; Heshka, S.; Albu, J.; Heymsfield, S.B.; Goodpaster, B.H.; Visser, M.; Harris, T.B.

2005-01-01

BACKGROUND: The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. OBJECTIVE: The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and

File list: His.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Unc.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Unc.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: His.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: His.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Unc.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: His.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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Biomarkers of Habitual Fish Intake in Adipose-Tissue

DEFF Research Database (Denmark)

Marckmann, P.; Lassen, Anne Dahl; Haraldsdottir, H.

1995-01-01

The association between habitual fish and marine n-3 polyunsaturated fatty acid (PUFA) intake, and the fatty acid composition of subcutaneous fat was studied in 24 healthy young volunteers. Habitual dietary intakes were estimated from three 7-d weighed food records made at months 0, 5, and 8...... of the 8-mo study period. The adipose tissue fatty acid composition of each individual was determined by gas chromatography as the mean of two gluteal biopsies, obtained in the first and the last month of the study. The daily consumption of fish and of marine n-3 PUFAs in absolute terms (g....../d) was significantly associated with adipose tissue docosahexaenoic acid content (DHA; r = 0.55 and 0.58, respectively, P acid contents. Our study indicates that the adipose tissue DHA content is the biomarker of choice for the assessment of long...

File list: Pol.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Adp.50.AllAg.Adipose_Tissue,_White hg19 RNA polymerase Adipocyte Adipose Tissue..., White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.50.AllAg.Adipose_Tissue,_White.bed ...

File list: Pol.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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File list: Pol.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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Initial Assessment of β3-Adrenoceptor-Activated Brown Adipose Tissue in Streptozotocin-Induced Type 1 Diabetes Rodent Model Using [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

Directory of Open Access Journals (Sweden)

Aparna Baranwal

2015-12-01

Full Text Available Metabolic activity of brown adipose tissue (BAT is activated by β3-adrenoceptor agonists and norepinephrine transporter (NET blockers and is measurable using [18F]fluorodeoxyglucose ([18F]FDG positron emission tomography/computed tomography (PET/CT in rats. Using the streptozotocin (STZ-treated rat model of type 1 diabetes mellitus (T1DM, we investigated BAT activity in this rat model under fasting and nonfasting conditions using [18F]FDG PET/CT. Drugs that enhance BAT activity may have a potential for therapeutic development in lowering blood sugar in insulin-resistant diabetes. Rats were rendered diabetic by administration of STZand confirmed by glucose measures. [18F]FDG was injected in the rats (fasted or nonfasted pretreated with either saline or β3-adrenoceptor agonist CL316,243 or the NET blocker atomoxetine for PET/CT scans. [18F]FDG metabolic activity was computed as standard uptake values (SUVs in interscapular brown adipose tissue (IBAT and compared across the different drug treatment conditions. Blood glucose levels > 500 mg/dL were established for the STZ-treated diabetic rats. Under fasting conditions, average uptake of [18F]FDG in the IBAT of STZ-treated diabetic rats was approximately 70% lower compared to that of normal rats. Both CL316,243 and atomoxetine activated IBAT in normal rats had an SUV > 5, whereas activation in STZ-treated rats was significantly lower. The agonist CL316,243 activated IBAT up to threefold compared to saline in the fasted STZ-treated rat. In the nonfasted rat, the IBAT activation was up by twofold by CL316243. Atomoxetine had a greater effect on lowering blood sugar levels compared to CL316,243 in the nonfasted rats. A significant reduction in metabolic activity was observed in the STZ-treated diabetic rodent model. Increased IBAT activity in the STZ-treated diabetic rat under nonfasted conditions using the β3-adrenoceptor agonist CL316,243 suggests a potential role of BAT in modulating blood sugar

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Adipose tissue content and distribution in children and adolescents with bronchial asthma.

Science.gov (United States)

Umławska, Wioleta

2015-02-01

The excess of adipose tissue and the pattern of adipose tissue distribution in the body seem to play an important role in the complicated dependencies between obesity and risk of developing asthma. The aim of the present study was to determine nutritional status in children and adolescents with bronchial asthma with special emphasis on adipose tissue distribution evaluated on the basis of skin-fold thicknesses, and to determine the relationships between patterns of adipose tissue distribution and the course of the disease. Anthropometric data on height, weight, circumferences and skin-fold thicknesses were extracted from the medical histories of 261 children diagnosed with asthma bronchitis. Values for children with asthma were compared to Polish national growth reference charts. Distribution of subcutaneous adipose tissue was evaluated using principal components analysis (PCA). Multivariate linear regression analyses tested the effect of three factors on subcutaneous adipose tissue distribution: type of asthma, the severity of the disease and the duration of the disease. Mean body height in the children examined in this study was lower than in their healthy peers. Mean BMI and skin-fold thicknesses were significantly higher and lean body mass was lower in the study group. Excess body fat was noted, especially in girls. Adipose tissue was preferentially deposited in the trunk in girls with severe asthma, as well as in those who had been suffering from asthma for a longer time. The type of asthma, atopic or non-atopic, had no observable effect on subcutaneous adipose tissue distribution in children examined. The data suggest that long-treated subjects and those with severe bronchial asthma accumulate more adipose tissue on the trunk. It is important to regularly monitor nutritional status in children with asthma, especially in those receiving high doses of systemic or inhaled glucocorticosteroids, and long-term treatment as well. Copyright © 2014 Elsevier Ltd. All

Myocardial regeneration potential of adipose tissue-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

2010-10-22

Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

Myocardial regeneration potential of adipose tissue-derived stem cells

International Nuclear Information System (INIS)

Bai, Xiaowen; Alt, Eckhard

2010-01-01

Research highlights: → Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. → For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. → This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying

File list: NoD.Adp.50.AllAg.Adipose_Tissue [Chip-atlas[Archive

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High intensity interval training improves liver and adipose tissue insulin sensitivity

Science.gov (United States)

Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

White adipose tissue: Getting nervous

NARCIS (Netherlands)

Fliers, E.; Kreier, F.; Voshol, P. J.; Havekes, L. M.; Sauerwein, H. P.; Kalsbeek, A.; Buijs, R. M.; Romijn, J. A.

2003-01-01

Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative

Degradation of brown adipocyte purine nucleotides regulates uncoupling protein 1 activity

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Tobias Fromme

2018-02-01

Full Text Available Objective: Non-shivering thermogenesis in mammalian brown adipose tissue depends on thermogenic uncoupling protein 1. Its activity is triggered by free fatty acids while purine nucleotides mediate inhibition. During activation, it is thought that free fatty acids overcome purine-mediated inhibition. We measured the cellular concentration and the release of purine nucleotide metabolites to uncover a possible role of purine nucleotide degradation in uncoupling protein 1 activation. Methods: With mass spectrometry, purine nucleotide metabolites were quantified in cellular homogenates and supernatants of cultured primary brown adipocytes. We also determined oxygen consumption in response to a β-adrenergic agonist. Results: Upon adrenergic activation, brown adipocytes decreased the intracellular concentration of inhibitory nucleotides (ATP, ADP, GTP and GDP and released the respective degradation products. At the same time, an increase in cellular calcium occurred. None of these phenomena occurred in white adipocytes or myotubes. The brown adipocyte expression of enzymes implicated in purine metabolic remodeling is altered upon cold exposure. Pharmacological and genetic interference of purine metabolism altered uncoupling protein 1 mediated uncoupled respiration. Conclusion: Adrenergic stimulation of brown adipocytes lowers the intracellular concentration of purine nucleotides, thereby contributing to uncoupling protein 1 activation. Keywords: Purine nucleotides, Uncoupling protein 1, Brown adipose tissue, Non-shivering thermogenesis, HILIC-MS/MS, Guanosine monophosphate reductase

Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism.

Science.gov (United States)

Alfadda, Assim A; Sallam, Reem M; Chishti, Muhammad Azhar; Moustafa, Amr S; Fatma, Sumbul; Alomaim, Waleed S; Al-Naami, Mohammed Y; Bassas, Abdulelah F; Chrousos, George P; Jo, Hyunsun

2012-06-01

Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.

The role of the brown adipose tissue in β3-adrenergic receptor activation-induced sleep, metabolic and feeding responses.

Science.gov (United States)

Szentirmai, Éva; Kapás, Levente

2017-04-19

Brown adipose tissue (BAT) is regulated by the sympathetic nervous system via β3-adrenergic receptors (β3-AR). Here we tested the hypothesis that pharmacological stimulation of β3-ARs leads to increased sleep in mice and if this change is BAT dependent. In wild-type (WT) animals, administration of CL-316,243, a selective β3-AR agonist, induced significant increases in non-rapid-eye movement sleep (NREMS) lasting for 4-10 h. Simultaneously, electroencephalographic slow-wave activity (SWA) was significantly decreased and body temperature was increased with a delay of 5-6 h. In uncoupling protein 1 (UCP-1) knockout mice, the middle and highest doses of the β3-AR agonist increased sleep and suppressed SWA, however, these effects were significantly attenuated and shorter-lasting as compared to WT animals. To determine if somnogenic signals arising from BAT in response to β3-AR stimulation are mediated by the sensory afferents of BAT, we tested the effects of CL-316,243 in mice with the chemical deafferentation of the intra-scapular BAT pads. Sleep responses to CL-316,243 were attenuated by ~50% in intra-BAT capsaicin-treated mice. Present findings indicate that the activation of BAT via β3-AR leads to increased sleep in mice and that this effect is dependent on the presence of UCP-1 protein and sleep responses require the intact sensory innervation of BAT.

Intrinsic regulation of blood flow in adipose tissue

DEFF Research Database (Denmark)

Henriksen, O; Nielsen, Steen Levin; Paaske, W

1976-01-01

Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated...... subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue...... vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (autoregulation), venous...

Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.

Science.gov (United States)

Park, Ye Seul; Uddin, Md Jamal; Piao, Lingjuan; Hwang, Inah; Lee, Jung Hwa; Ha, Hunjoo

2016-01-01

Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.

Novel GLP-1 Analog Supaglutide Reduces HFD-Induced Obesity Associated with Increased Ucp-1 in White Adipose Tissue in Mice

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Yun Wan

2017-05-01

Full Text Available GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice. Mice were fed with high-fat diet (HFD for 6 months to induce obesity and then subjected to supaglutide treatment (300 μg/kg, bi-weekly for 4 weeks, and placebo as control. Metabolic conditions were monitored and energy expenditure was assessed by indirect calorimetry (CLAMS. Cold tolerance test was performed to evaluate brown-adipose tissue (BAT activities in response to cold challenge. Glucose tolerance and insulin resistance were evaluated by intraperitoneal glucose tolerance test and insulin tolerance tests. Liver and adipose tissues were collected for histology analysis. Expression of uncoupling protein 1(Ucp1 in adipose tissues was evaluated by Western blotting. We found that supaglutide treatment reduced body weight, which was associated with reduced food intake. Compared to the placebo control, supaglutide treatment improved lipid profile, i.e., significantly decreased circulating total cholesterol levels, declined serum triglyceride, and free fatty acid levels. Importantly, the intervention significantly reduced fatty liver, decreased liver triglyceride content, and concomitantly ameliorated liver injury exemplified by declined hepatic alanine aminotransferase (ALT and aspartic transaminase (AST content. Remarkably, supaglutide reduced hepatic lipid accumulation and altered morphometry in favor of small adipocytes in fat. This is consistent with the observation that

Regulation of Brown and White Adipocyte Transcriptome by the Transcriptional Coactivator NT-PGC-1α.

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Jihyun Kim

Full Text Available The β3-adrenergic receptor (AR signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β3-AR signaling highly induces the expression of transcriptional coactivator PGC-1α and its splice variant N-terminal (NT-PGC-1α, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of transcription factors. We previously reported that NT-PGC-1α is able to increase mitochondrial number and activity in cultured brown adipocytes by promoting the expression of mitochondrial and thermogenic genes. In the present study, we performed genome-wide profiling of NT-PGC-1α-responsive genes in brown adipocytes to identify genes potentially regulated by NT-PGC-1α. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, canonical pathway analysis of NT-PGC-1α-responsive genes identified several metabolic pathways including glycolysis and fatty acid synthesis. In order to validate the identified genes in vivo, we utilized the FL-PGC-1α-/- mouse that is deficient in full-length PGC-1α (FL-PGC-1α but expresses a slightly shorter and functionally equivalent form of NT-PGC-1α (NT-PGC-1α254. The β3-AR-induced increase of NT-PGC-1α254 in FL-PGC-1α-/- brown and white adipose tissue was closely associated with elevated expression of genes involved in thermogenesis, mitochondrial oxidative metabolism, glycolysis and fatty acid synthesis. Increased adipose tissue thermogenesis by β3-AR activation resulted in attenuation of adipose tissue expansion in FL-PGC-1α-/- adipose tissue under the high-fat diet condition. Together, the data strengthen our previous findings that NT-PGC-1�

Developmental programming, adiposity, and reproduction in ruminants.

Science.gov (United States)

Symonds, M E; Dellschaft, N; Pope, M; Birtwistle, M; Alagal, R; Keisler, D; Budge, H

2016-07-01

Although sheep have been widely adopted as an animal model for examining the timing of nutritional interventions through pregnancy on the short- and long-term outcomes, only modest programming effects have been seen. This is due in part to the mismatch in numbers of twins and singletons between study groups as well as unequal numbers of males and females. Placental growth differs between singleton and twin pregnancies which can result in different body composition in the offspring. One tissue that is especially affected is adipose tissue which in the sheep fetus is primarily located around the kidneys and heart plus the sternal/neck region. Its main role is the rapid generation of heat due to activation of the brown adipose tissue-specific uncoupling protein 1 at birth. The fetal adipose tissue response to suboptimal maternal food intake at defined stages of development differs between the perirenal abdominal and pericardial depots, with the latter being more sensitive. Fetal adipose tissue growth may be mediated in part by changes in leptin status of the mother which are paralleled in the fetus. Then, over the first month of life plasma leptin is higher in females than males despite similar adiposity, when fat is the fastest growing tissue with the sternal/neck depot retaining uncoupling protein 1, whereas other depots do not. Future studies should take into account the respective effects of fetal number and sex to provide more detailed insights into the mechanisms by which adipose and related tissues can be programmed in utero. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of training state on fasting-induced regulation of adipose tissue metabolism in humans

DEFF Research Database (Denmark)

Bertholdt, Lærke; Gudiksen, Anders; Stankiewicz, Tomasz

2018-01-01

Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study was to investig......Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study...... was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue. Untrained (VO2max 55ml......RNA content were higher in trained subjects than untrained subjects. In addition, trained subjects had higher adipose tissue hormone sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein content as well as higher plasma free fatty acids concentration than untrained subjects during...

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

Science.gov (United States)

Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

2017-12-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

Cell supermarket: Adipose tissue as a source of stem cells

Science.gov (United States)

Adipose tissue is derived from numerous sources, and in recent years has been shown to provide numerous cells from what seemingly was a population of homogeneous adipocytes. Considering the types of cells that adipose tissue-derived cells may form, these cells may be useful in a variety of clinical ...

Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

Directory of Open Access Journals (Sweden)

Kamila Wojciechowicz

Full Text Available The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16 the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis, under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

File list: ALL.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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From the Cover: Adipose tissue mass can be regulated through the vasculature

Science.gov (United States)

Rupnick, Maria A.; Panigrahy, Dipak; Zhang, Chen-Yu; Dallabrida, Susan M.; Lowell, Bradford B.; Langer, Robert; Judah Folkman, M.

2002-08-01

Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.

Adipose stem cells for bone tissue repair

OpenAIRE

Ciuffi, Simone; Zonefrati, Roberto; Brandi, Maria Luisa

2017-01-01

Adipose-derived stem/stromal cells (ASCs), together with adipocytes, vascular endothelial cells, and vascular smooth muscle cells, are contained in fat tissue. ASCs, like the human bone marrow stromal/stem cells (BMSCs), can differentiate into several lineages (adipose cells, fibroblast, chondrocytes, osteoblasts, neuronal cells, endothelial cells, myocytes, and cardiomyocytes). They have also been shown to be immunoprivileged, and genetically stable in long-term cultures. Nevertheless, unlik...

Adipose tissue macrophages impair preadipocyte differentiation in humans.

Directory of Open Access Journals (Sweden)

Li Fen Liu

Full Text Available The physiologic mechanisms underlying the relationship between obesity and insulin resistance are not fully understood. Impaired adipocyte differentiation and localized inflammation characterize adipose tissue from obese, insulin-resistant humans. The directionality of this relationship is not known, however. The aim of the current study was to investigate whether adipose tissue inflammation is causally-related to impaired adipocyte differentiation.Abdominal subcutaneous(SAT and visceral(VAT adipose tissue was obtained from 20 human participants undergoing bariatric surgery. Preadipocytes were isolated, and cultured in the presence or absence of CD14+ macrophages obtained from the same adipose tissue sample. Adipocyte differentiation was quantified after 14 days via immunofluorescence, Oil-Red O, and adipogenic gene expression. Cytokine secretion by mature adipocytes cultured with or without CD14+macrophages was quantified.Adipocyte differentiation was significantly lower in VAT than SAT by all measures (p<0.001. With macrophage removal, SAT preadipocyte differentiation increased significantly as measured by immunofluorescence and gene expression, whereas VAT preadipocyte differentiation was unchanged. Adipocyte-secreted proinflammatory cytokines were higher and adiponectin lower in media from VAT vs SAT: macrophage removal reduced inflammatory cytokine and increased adiponectin secretion from both SAT and VAT adipocytes. Differentiation of preadipocytes from SAT but not VAT correlated inversely with systemic insulin resistance.The current results reveal that proinflammatory immune cells in human SAT are causally-related to impaired preadipocyte differentiation, which in turn is associated with systemic insulin resistance. In VAT, preadipocyte differentiation is poor even in the absence of tissue macrophages, pointing to inherent differences in fat storage potential between the two depots.

Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure

NARCIS (Netherlands)

Oedayrajsingh-Varma, M. J.; van Ham, S. M.; Knippenberg, M.; Helder, M. N.; Klein-Nulend, J.; Schouten, T. E.; Ritt, M. J. P. F.; van Milligen, F. J.

2006-01-01

Adipose tissue contains a stromal vascular fraction that can be easily isolated and provides a rich source of adipose tissue-derived mesenchymal stem cells (ASC). These ASC are a potential source of cells for tissue engineering. We studied whether the yield and growth characteristics of ASC were

Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

DEFF Research Database (Denmark)

Ahlqvist, Emma; Osmark, Peter; Kuulasmaa, Tiina

2013-01-01

Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis...... and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher...... for transmembrane activity. Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue...

Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

Science.gov (United States)

Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

2017-09-01

Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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The relationship between bone mineral density and adipose tissue of postmenopausal women

Energy Technology Data Exchange (ETDEWEB)

Kim, Sun Hwa [Dept. of Radiology, HwaMyeong Iisin christian Hospital, Busan (Korea, Republic of); Kim, Jung Hoon [Dept. of Radiological Science, Catholic University of Pusan, Busan (Korea, Republic of); Im, In Chul [Dept. of Radiological Science, Dong Eui University, Busan (Korea, Republic of)

2017-06-15

Postmenopausal women are at increased risk for osteoporosis and obesity due to changes in hormones. The relationship between osteoporosis and body weight is known, and its relation with body fat mass is discussed. The purpose of this study was to evaluate the bone mineral density(BMD) changes of epicardial adipose tissue(EAT) and abdominal subcutaneous fat. The subjects of this study were 160 postmenopausal women who underwent BMD and echocardiography. The thickness of the epicardial adipose tissue was measured in three sections and the BMD were meassured according to the diagnostic criteria. The results of this study that age increase the risk of osteoporosis increases, and as the weight and BMI decrease, the risk of osteoporosis increases(p<0.05). The relationship between changes in bone mineral density and adipose tissue in postmenopausal women, increased epicardial adipose tissue was negatively correlated with the bone mineral density(p<0.05). conversely, increased abdominal subcutaneous fat thickness was positively correlated with bone mineral density(p<0.05). In other words, the effect of bone mineral density on the location of adipose tissue was different. If Echocardiography is used to periodically examine changes in the thickness of the epicardial adipose tissue, it may be prevented before proceeding to osteoporosis.

Inhibition of myostatin in mice improves insulin sensitivity via irisin-mediated cross talk between muscle and adipose tissues.

Science.gov (United States)

Dong, Jiangling; Dong, Yanjun; Dong, Yanlan; Chen, Fang; Mitch, William E; Zhang, Liping

2016-03-01

In mice, a high-fat diet (HFD) induces obesity, insulin resistance and myostatin production. We tested whether inhibition of myostatin in mice can reverse these HFD-induced abnormalities. C57BL/6 mice were fed a HFD for 16 weeks including the final 4 weeks some mice were treated with an anti-myostatin peptibody. Body composition, the respiratory exchange ratio plus glucose and insulin tolerance tests were examined. Myostatin knock down in C2C12 cells was performed using small hairpin RNA lentivirus. Adipose tissue-derived stem cells were cultured to measure their responses to conditioned media from C2C12 cells lacking myostatin, or to recombinant myostatin or irisin. Isolated peritoneal macrophages were treated with myostatin or irisin to determine whether myostatin or irisin induce inflammatory mechanisms. In HFD-fed mice, peptibody treatment stimulated muscle growth and improved insulin resistance. The improved glucose and insulin tolerances were confirmed when we found increased muscle expression of p-Akt and the glucose transporter, Glut4. In HFD-fed mice, the peptibody suppressed macrophage infiltration and the expression of proinflammatory cytokines in both the muscle and adipocytes. Inhibition of myostatin caused the conversion of white (WAT) to brown adipose tissue, whereas stimulating fatty acid oxidation and increasing energy expenditure. The related mechanism is a muscle-to-fat cross talk mediated by irisin. Myostatin inhibition increased peroxisome proliferator-activated receptor gamma, coactivator 1α expression and irisin production in the muscle. Irisin then stimulated WAT browning. Irisin also suppresses inflammation and stimulates macrophage polarization from M1 to M2 types. These results uncover a metabolic pathway from an increase in myostatin that suppresses irisin leading to the activation of inflammatory cytokines and insulin resistance. Thus, myostatin is a potential therapeutic target to treat insulin resistance of type II diabetes as well

High intensity interval training improves liver and adipose tissue insulin sensitivity

Directory of Open Access Journals (Sweden)

Katarina Marcinko

2015-12-01

Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction

Directory of Open Access Journals (Sweden)

Marco Calogero Amato

2014-01-01

Full Text Available The Visceral Adiposity Index (VAI has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk.

In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

Science.gov (United States)

Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

2013-04-01

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

DEFF Research Database (Denmark)

Arngrim, Nanna Bjørkbom; Simonsen, L; Holst, J J

2013-01-01

The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

Relationship between reflection spectra of breast adipose tissue with histologic grade

Science.gov (United States)

Muñoz Morales, Aarón; Vázquez Y Montiel, Sergio; Reigosa, Aldo

2011-08-01

Optical spectroscopy allows the characterization, recognition and differentiation of subcutaneous tissues healthy and no-healthy, to facilitate the diagnosis or early detection for breast cancer are studied white adipose tissue by the subcutaneous region with the help of the diffuse reflection spectroscopy in the visible areas (400 to 700 nm) of electromagnetic spectrum for them using a spectrometer portable of integrating sphere, Hunter lab Model Mini-Scan. The problem to be solved for cancer detection by optical techniques is to find the solution to the inverse problem of scattering of radiation in tissue where it is necessary to solve the equation of energy transfer. us through the trigonometric interpolation and by the data adjustment by least squares using Fourier series expansion to parameterize the spectral response curves of each sample of breast adipose tissue then correlated with histological grades established by the optical biopsy for each one of the samples, allowing use this technique to the study of anomalies in White Adipose Tissue Breast, changes are evident in the spectral response for Breast Adipose Tissue carcinogens with respect to healthy tissues and for the different histological grades.

Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

DEFF Research Database (Denmark)

Mulla, N A; Simonsen, L; Bülow, J

2000-01-01

, a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease......One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...... metabolism during a 3 h post-exercise period. Six subjects were studied twice. In one experiment, they exercised for 90 min at 40% of maximal O2 consumption (VO2,max) and in the other experiment they exercised at 60% VO2,max for 60 min. For both experiments, catheters were inserted in an artery...

Determination of the tissue-to-blood partition coefficient for 131iodo-antipyrine in human subcutaneous adipose tissue

DEFF Research Database (Denmark)

Jelnes, R; Astrup, A

1985-01-01

131Iodo-antipyrine (131I-AP) is commonly used for blood flow measurements in adipose tissue. These estimations have been based on the assumption of the tissue-to-blood partition coefficient being 1 ml g-1. No exact determination of the tissue-to-blood partition coefficient for 131I-AP in adipose...... tissue has been carried out. In the present study a partition coefficient of 1.12 +/- 0.06 (mean +/- S.D.) for 131I-AP in adipose tissue has been determined based on the partition coefficient for 131I-AP between lipid-saline (1.24 ml g-1), red blood cells-plasma (0.64 ml g-1), protein-saline (0.19 ml g-1...

Effect of luminescence transport through adipose tissue on measurement of tissue temperature by using ZnCdS nanothermometers

Science.gov (United States)

Volkova, Elena K.; Yanina, Irina Yu.; Sagaydachnaya, Elena; Konyukhova, Julia G.; Kochubey, Vyacheslav I.; Tuchin, Valery V.

2018-02-01

The spectra of luminescence of ZnCdS nanoparticles (ZnCdS NPs) were measured and analyzed in a wide temperature range: from room to human body and further to a hyperthermic temperature resulting in tissue morphology change. The results show that the signal of luminescence of ZnCdS NPs placed within the tissue is reasonably good sensitive to temperature change and accompanied by phase transitions of lipid structures of adipose tissue. It is shown that the presence of a phase transition in adipose tissue upon its heating (polymorphic transformations of lipids) leads to a nonmonotonic temperature dependence of the intensity of luminescence for the nanoparticles introduced into adipose tissue. This is due to a change in the light scattering by the tissue. The light scattering of adipose tissue greatly distorts the results of temperature measurements. The application of these nanoparticles is possible for temperature measurements in very thin or weakly scattering samples.

Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue.

Science.gov (United States)

Koban, Michael; Swinson, Kevin L

2005-07-01

A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.

A role for TLR10 in obesity and adipose tissue morphology

NARCIS (Netherlands)

Boutens, Lily; Mirea, Andreea Manuela; Munckhof, van den Inge; Doppenberg-Oosting, Marije; Jaeger, Martin; Hijmans, Anneke; Netea, Mihai G.; Joosten, Leo A.B.; Stienstra, Rinke

2018-01-01

Toll like receptors (TLRs) are expressed in adipose tissue and promote adipose tissue inflammation during obesity. Recently, anti-inflammatory properties have been attributed to TLR10 in myeloid cells, the only member of the TLR family with inhibitory activity. In order to assess whether

Biology and function of adipose tissue macrophages, dendritic cells and B cells.

Science.gov (United States)

Ivanov, Stoyan; Merlin, Johanna; Lee, Man Kit Sam; Murphy, Andrew J; Guinamard, Rodolphe R

2018-04-01

The increasing incidence of obesity and its socio-economical impact is a global health issue due to its associated co-morbidities, namely diabetes and cardiovascular disease [1-5]. Obesity is characterized by an increase in adipose tissue, which promotes the recruitment of immune cells resulting in low-grade inflammation and dysfunctional metabolism. Macrophages are the most abundant immune cells in the adipose tissue of mice and humans. The adipose tissue also contains other myeloid cells (dendritic cells (DC) and neutrophils) and to a lesser extent lymphocyte populations, including T cells, B cells, Natural Killer (NK) and Natural Killer T (NKT) cells. While the majority of studies have linked adipose tissue macrophages (ATM) to the development of low-grade inflammation and co-morbidities associated with obesity, emerging evidence suggests for a role of other immune cells within the adipose tissue that may act in part by supporting macrophage homeostasis. In this review, we summarize the current knowledge of the functions ATMs, DCs and B cells possess during steady-state and obesity. Copyright © 2018 Elsevier B.V. All rights reserved.

Diurnal gene expression of lipolytic natriuretic peptide receptors in white adipose tissue

DEFF Research Database (Denmark)

Smith, Julie; Fahrenkrug, Jan; Jørgensen, Henrik L

2015-01-01

Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart, but the tem......Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart......, but the temporal expression profile of their cognate receptors has not been examined in white adipose tissue. We therefore collected peri-renal white adipose tissue and serum from WT mice. Tissue mRNA contents of NPRs - NPR-A and NPR-C, the clock genes Per1 and Bmal1, and transcripts involved in lipid metabolism...... in serum peaked in the active dark period (P=0.003). In conclusion, NPR-A and NPR-C gene expression is associated with the expression of clock genes in white adipose tissue. The reciprocal expression may thus contribute to regulate lipolysis and energy homeostasis in a diurnal manner....

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

Science.gov (United States)

Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Adipose tissue Fatty Acid patterns and changes in antrhropometry

DEFF Research Database (Denmark)

Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

2011-01-01

Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...... in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate...... the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WCBMI), adjusting for confounders. Results 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men...

Feast and famine: Adipose tissue adaptations for healthy aging.

Science.gov (United States)

Lettieri Barbato, Daniele; Aquilano, Katia

2016-07-01

Proper adipose tissue function controls energy balance with favourable effects on metabolic health and longevity. The molecular and metabolic asset of adipose tissue quickly and dynamically readapts in response to nutrient fluctuations. Once delivered into cells, nutrients are managed by mitochondria that represent a key bioenergetics node. A persistent nutrient overload generates mitochondrial exhaustion and uncontrolled reactive oxygen species ((mt)ROS) production. In adipocytes, metabolic/molecular reorganization is triggered culminating in the acquirement of a hypertrophic and hypersecretory phenotype that accelerates aging. Conversely, dietary regimens such as caloric restriction or time-controlled fasting endorse mitochondrial functionality and (mt)ROS-mediated signalling, thus promoting geroprotection. In this perspective view, we argued some important molecular and metabolic aspects related to adipocyte response to nutrient stress. Finally we delineated hypothetical routes by which molecularly and metabolically readapted adipose tissue promotes healthy aging. Copyright © 2016 Elsevier B.V. All rights reserved.

Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications.

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Kargi, Atil Y; Iacobellis, Gianluca

2014-01-01

Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or "adipokines" have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of "cross talk" between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

Directory of Open Access Journals (Sweden)

Atil Y. Kargi

2014-01-01

Full Text Available Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or “adipokines” have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of “cross talk” between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

Disconnect Between Adipose Tissue Inflammation and Cardiometabolic Dysfunction in Ossabaw Pigs

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Vieira-Potter, Victoria J.; Lee, Sewon; Bayless, David S.; Scroggins, Rebecca J.; Welly, Rebecca J.; Fleming, Nicholas J.; Smith, Thomas N.; Meers, Grace M.; Hill, Michael A.; Rector, R. Scott; Padilla, Jaume

2015-01-01

Objective The Ossabaw pig is emerging as an attractive model of human cardiometabolic disease due to its size and susceptibility to atherosclerosis, among other characteristics. Here we investigated the relationship between adipose tissue inflammation and metabolic dysfunction in this model. Methods Young female Ossabaw pigs were fed a western-style high-fat diet (HFD) (n=4) or control low-fat diet (LFD) (n=4) for a period of 9 months and compared for cardiometabolic outcomes and adipose tissue inflammation. Results The HFD-fed “OBESE” pigs were 2.5 times heavier (p<0.001) than LFD-fed “LEAN” pigs and developed severe obesity. HFD-feeding caused pronounced dyslipidemia, hypertension, insulin resistance (systemic and adipose) as well as induction of inflammatory genes, impairments in vasomotor reactivity to insulin and atherosclerosis in the coronary arteries. Remarkably, visceral, subcutaneous and perivascular adipose tissue inflammation (via FACS analysis and RT-PCR) was not increased in OBESE pigs, nor were circulating inflammatory cytokines. Conclusions These findings reveal a disconnect between adipose tissue inflammation and cardiometabolic dysfunction induced by western diet feeding in the Ossabaw pig model. PMID:26524201

Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice

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Hesselbarth, Nico; Pettinelli, Chiara; Gericke, Martin; Berger, Claudia; Kunath, Anne; Stumvoll, Michael; Blüher, Matthias; Klöting, Nora

2015-01-01

Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA 1c , triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA 1c , triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition

Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan.

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Sun, Lijuan; Camps, Stefan G; Goh, Hui Jen; Govindharajulu, Priya; Schaefferkoetter, Joshua D; Townsend, David W; Verma, Sanjay K; Velan, S Sendhil; Sun, Lei; Sze, Siu Kwan; Lim, Su Chi; Boehm, Bernhard Otto; Henry, Christiani Jeyakumar; Leow, Melvin Khee-Shing

2018-01-01

Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). We compared capsinoids and cold exposure on BAT activation and whole-body EE. Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or ≤2 h of cold exposure (∼14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442. © 2018 American Society for Nutrition. All rights reserved.

Tissue/blood partition coefficients for xenon in various adipose tissue depots in man

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Bülow, J; Jelnes, Rolf; Astrup, A

1987-01-01

Tissue/blood partition coefficients (lambda) for xenon were calculated for subcutaneous adipose tissue from the abdominal wall and the thigh, and for the perirenal adipose tissue after chemical analysis of the tissues for lipid, water and protein content. The lambda in the perirenal tissue...... was found to correlate linearly to the relative body weight (RBW) in per cent with the regression equation lambda = 0.045 . RBW + 0.99. The subcutaneous lambda on the abdomen correlated linearly to the local skinfold thickness (SFT) with the equation lambda = 0.22 SFT + 2.99. Similarly lambda on the thigh...... correlated to SFT with the equation lambda = 0.20 . SFT + 4.63. It is concluded that the previously accepted lambda value of 10 is generally too high in perirenal as well as in subcutaneous tissue. Thus, by application of the present regression equations, it is possible to obtain more exact estimates...

Transcription regulator TRIP-Br2 mediates ER stress-induced brown adipocytes dysfunction.

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Qiang, Guifen; Whang Kong, Hyerim; Gil, Victoria; Liew, Chong Wee

2017-01-09

In contrast to white adipose tissue, brown adipose tissue (BAT) is known to play critical roles for both basal and inducible energy expenditure. Obesity is associated with reduction of BAT function; however, it is not well understood how obesity promotes BAT dysfunction, especially at the molecular level. Here we show that the transcription regulator TRIP-Br2 mediates ER stress-induced inhibition of lipolysis and thermogenesis in BAT. Using in vitro, ex vivo, and in vivo approaches, we demonstrate that obesity-induced inflammation upregulates brown adipocytes TRIP-Br2 expression via the ER stress pathway and amelioration of ER stress in mice completely abolishes high fat diet-induced upregulation of TRIP-Br2 in BAT. We find that increased TRIP-Br2 significantly inhibits brown adipocytes thermogenesis. Finally, we show that ablation of TRIP-Br2 ameliorates ER stress-induced inhibition on lipolysis, fatty acid oxidation, oxidative metabolism, and thermogenesis in brown adipocytes. Taken together, our current study demonstrates a role for TRIP-Br2 in ER stress-induced BAT dysfunction, and inhibiting TRIP-Br2 could be a potential approach for counteracting obesity-induced BAT dysfunction.

Pituitary adenoma with adipose tissue: A new metaplastic variant.

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Caporalini, Chiara; Buccoliero, Anna Maria; Pansini, Luigi; Moscardi, Selene; Novelli, Luca; Baroni, Gianna; Bordi, Lorenzo; Ammannati, Franco; Taddei, Gian Luigi

2017-08-01

Pituitary adenomas are benign tumors representing approximately 15-20% of intracranial neoplasms. There have been few reports of metaplastic osseous transformation and about 60 cases of neuronal metaplasia in pituitary adenoma but adipose metaplasia has not been previously described in the English literature. Here we report a case of pituitary adenoma with metaplastic adipose tissue in a 58-year-old male patient. Histologically this case fulfilled the criteria of a non-functioning pituitary adenoma, and moreover a central area of adipose tissue, made by mature adipocytes, and many tumor cells, containing fat droplet were evident. Lipomatous transformation of tumor cells in the CNS has been previously observed but, to the best of our knowledge, our case is the first pituitary adenoma with such change. The histogenesis of the adipose element in pituitary adenoma is not well understood, and could be a result of a metaplastic change or divergent differentiation from a common progenitor cell. © 2017 Japanese Society of Neuropathology.

Apolipoprotein CIII overexpression exacerbates diet-induced obesity due to adipose tissue higher exogenous lipid uptake and retention and lower lipolysis rates.

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Raposo, Helena F; Paiva, Adriene A; Kato, Larissa S; de Oliveira, Helena C F

2015-01-01

Hypertriglyceridemia is a common type of dyslipidemia found in obesity. However, it is not established whether primary hyperlipidemia can predispose to obesity. Evidences have suggested that proteins primarily related to plasma lipoprotein transport, such as apolipoprotein (apo) CIII and E, may significantly affect the process of body fat accumulation. We have previously observed an increased adiposity in response to a high fat diet (HFD) in mice overexpressing apoCIII. Here, we examined the potential mechanisms involved in this exacerbated response of apoCIII mice to the HFD. We measured body energy balance, tissue capacity to store exogenous lipids, lipogenesis and lipolysis rates in non-transgenic and apoCIII overexpressing mice fed a HFD during two months. Food intake, fat excretion and whole body CO2 production were similar in both groups. However, the adipose tissue mass (45 %) and leptin plasma levels (2-fold) were significantly greater in apoCIII mice. Lipogenesis rates were similar, while exogenous lipid retention was increased in perigonadal (2-fold) and brown adipose tissues (40 %) of apoCIII mice. In addition, adipocyte basal lipolysis (55 %) and in vivo lipolysis index (30 %) were significantly decreased in apoCIII mice. A fat tolerance test evidenced delayed plasma triglyceride clearance and greater transient availability of non-esterified fatty acids (NEFA) during the post-prandial state in the apoCIII mice plasma. Thus, apoCIII overexpression resulted in increased NEFA availability to adipose uptake and decreased adipocyte lipolysis, favoring lipid enlargement of adipose depots. We propose that plasma apoCIII levels represent a new risk factor for diet-induced obesity.

Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue

DEFF Research Database (Denmark)

Stallknecht, B; Simonsen, L; Bülow, J

1995-01-01

glycerol concentrations (Tr: 129 +/- 36 microM; Sed: 119 +/- 56) did not differ between groups. It is concluded that in intact subcutaneous adipose tissue epinephrine-stimulated blood flow is enhanced, whereas lipolytic sensitivity to epinephrine is the same in trained compared with untrained subjects.......Trained humans (Tr) have a higher fat oxidation during submaximal physical work than sedentary humans (Sed). To investigate whether this reflects a higher adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six...... sedentary young men. Glycerol was measured in arterial blood, and intercellular glycerol concentrations in abdominal subcutaneous adipose tissue were measured by microdialysis. Adipose tissue blood flow was measured by 133Xe-washout technique. From these measurements adipose tissue lipolysis was calculated...

Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS).

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Borruel, Susana; Fernández-Durán, Elena; Alpañés, Macarena; Martí, David; Alvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2013-03-01

Sexual dimorphism suggests a role for androgens in body fat distribution. Women with polycystic ovary syndrome (PCOS), a mainly androgen excess disorder, often present with abdominal obesity and visceral adiposity. We hypothesized that women with PCOS have a masculinized body fat distribution favoring the deposition of fat in visceral and organ-specific adipose tissue depots. This was a case-control study. The study was conducted at an academic hospital. Women with PCOS (n = 55), women without androgen excess (n = 25), and men (n = 26) presenting with similar body mass index participated in the study. There were no interventions. Ultrasound measurements of adipose tissue depots including sc (minimum and maximum), preperitoneal, ip, mesenteric, epicardial, and perirenal fat thickness were obtained and total body fat mass was estimated using a body fat monitor. Men and patients with PCOS had increased amounts of total body fat compared with control women. Men had increased thickness of intraabdominal adipose tissue depots compared with the control women, with the women with PCOS showing intermediate values that were also higher than those of control women in the case of ip and mesenteric fat thickness and was close to reaching statistical significance in the case of epicardial fat thickness. Women with PCOS also showed increased minimum sc fat thickness compared with the control women. Obesity increased the thickness of all of the adipose tissue depots in the 3 groups of subjects. Women with PCOS have higher global adiposity and increased amounts of visceral adipose tissue compared with control women, especially in the ip and mesenteric depots.

Substance for thermoluminescent dosimetry of photon radiation in adipose tissue

International Nuclear Information System (INIS)

Kalmykov, L.Z.; Kandel', T.G.

1983-01-01

Substance composition for thermoluminescent photon dosimetry in adipose tissue is proposed which makes it possible to simplify dosimetric measurements and to improve their accuracy. The substance consists of powder-like thermoluminophor Li 2 B 4 O 7 (0.03%Mn) 48-52 mass % and bistriethylammonium dodecahydrododecaborane - 48-52 mass %. The above substance is equivalent in respect to dosimetry to adipose tissue within the 10 keV - 10 MeV energy range

Low-protein, high-carbohydrate diet increases glucose uptake and fatty acid synthesis in brown adipose tissue of rats.

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Aparecida de França, Suélem; Pavani Dos Santos, Maísa; Nunes Queiroz da Costa, Roger Vinícius; Froelich, Mendalli; Buzelle, Samyra Lopes; Chaves, Valéria Ernestânia; Giordani, Morenna Alana; Pereira, Mayara Peron; Colodel, Edson Moleta; Marlise Balbinotti Andrade, Cláudia; Kawashita, Nair Honda

2014-04-01

The aim of this study was to evaluate glucose uptake and the contribution of glucose to fatty acid (FA) synthesis and the glycerol-3-phosphate (G3P) of triacylglycerol synthesis by interscapular brown adipose tissue (IBAT) of low-protein, high-carbohydrate (LPHC) diet-fed rats. LPHC (6% protein; 74% carbohydrate) or control (17% protein; 63% carbohydrate) diets were administered to rats (∼ 100 g) for 15 d. Total FA and G3P synthesis and the synthesis of FA and G3P from glucose were evaluated in vivo by (3)H2O and (14)C-glucose. Sympathetic neural contribution for FA synthesis was evaluated by comparing the synthesis in denervated (7 d before) IBAT with that of the contralateral innervated side. The insulin signaling and β3 adrenergic receptor (β3-AR) contents, as well as others, were determined by Western blot (Student's t test or analysis of variance; P ≤ 0.05). Total FA synthesis in IBAT was 133% higher in the LPHC group and was reduced 85% and 70% by denervation for the LPHC and control groups, respectively. Glucose uptake was 3.5-fold higher in the IBAT of LPHC rats than in that of the control rats, and the contribution of glucose to the total FA synthesis increased by 12% in control rats compared with 18% in LPHC rats. The LPHC diet increased the G3P generation from glucose by 270% and the insulin receptor content and the p-AKT insulin stimulation in IBAT by 120% and reduced the β3-AR content by 50%. The LPHC diet stimulated glucose uptake, both the total rates and the rates derived from glucose-dependent FA and G3P synthesis, by increasing the insulin sensitivity and the sympathetic flux, despite a reduction in the β3-AR content. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of Maternal Melatonin Suppression on Amount and Functionality of Brown Adipose Tissue (BAT) in the Newborn Sheep.

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Seron-Ferre, Maria; Reynolds, Henry; Mendez, Natalia Andrea; Mondaca, Mauricio; Valenzuela, Francisco; Ebensperger, Renato; Valenzuela, Guillermo J; Herrera, Emilio A; Llanos, Anibal J; Torres-Farfan, Claudia

2014-01-01

In human and sheep newborns, brown adipose tissue (BAT) accrued during fetal development is used for newborn thermogenesis. Here, we explored the role of maternal melatonin during gestation on the amount and functionality of BAT in the neonate. We studied BAT from six lambs gestated by ewes exposed to constant light from 63% gestation until delivery to suppress melatonin (LL), six lambs gestated by ewes exposed to LL but receiving daily oral melatonin (12 mg at 1700 h, LL + Mel) and another six control lambs gestated by ewes maintained in 12 h light:12 h dark (LD). Lambs were instrumented at 2 days of age. At 4-6 days of age, they were exposed to 24°C (thermal neutrality conditions) for 1 h, 4°C for 1 h, and 24°C for 1 h. Afterward, lambs were euthanized and BAT was dissected for mRNA measurement, histology, and ex vivo experiments. LL newborns had lower central BAT and skin temperature under thermal neutrality and at 4°C, and higher plasma norepinephrine concentration than LD newborns. In response to 4°C, they had a pronounced decrease in skin temperature and did not increase plasma glycerol. BAT weight in LL newborns was about half of that of LD newborns. Ex vivo, BAT from LL newborns showed increased basal lipolysis and did not respond to NE. In addition, expression of adipogenic/thermogenic genes (UCP1, ADBR3, PPARγ, PPARα, PGC1α, C/EBPβ, and perilipin) and of the clock genes Bmal1, Clock, and Per2 was increased. Remarkably, the effects observed in LL newborns were absent in LL + Mel newborns. Thus, our results support that maternal melatonin during gestation is important in determining amount and normal functionality of BAT in the neonate.

Human brown adipose tissue [15O]O2 PET imaging in the presence and absence of cold stimulus

International Nuclear Information System (INIS)

Din, Mueez U; Raiko, Juho; Saari, Teemu; Tolvanen, Tuula; Oikonen, Vesa; Teuho, Jarmo; Sipilae, Hannu T.; Savisto, Nina; Nuutila, Pirjo; Virtanen, Kirsi A.; Kudomi, Nobu; Parkkola, Riitta

2016-01-01

Brown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [ 15 O]O 2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE. Seven healthy study subjects were studied at two different scanning sessions, (1) at room temperature (RT) and (2) with acute cold exposure. Radiotracers [ 15 O]O 2 , [ 15 O]H 2 O, and [ 18 F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold. BAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2-47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus. Our study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake. (orig.)

Impact of maternal melatonin suppression on amount and functionality of brown adipose tissue (BAT in the newborn sheep.

Directory of Open Access Journals (Sweden)

Maria eSeron-Ferre

2015-01-01

Full Text Available In human and sheep newborns, brown adipose tissue (BAT accrued during fetal development is used for newborn thermogenesis. Here we explored the role of maternal melatonin during gestation on the amount and functionality of BAT in the neonate. We studied BAT from 6 lambs gestated by ewes exposed to constant light from 63% gestation until delivery to suppress melatonin (LL, 6 lambs gestated by ewes exposed to LL but receiving daily oral melatonin (12mg at 1700 hrs, LL+Mel and another 6 control lambs gestated by ewes maintained in 12h light:12h dark (LD. Lambs were in-strumented at 2 days of age. At 4-6 days of age, they were exposed to 24ºC (thermal neutrality condi-tions for 1 hr, 4ºC for 1 hr and 24ºC for 1 hr. Afterward, lambs were euthanized and BAT was dissected for mRNA measurement, histology and ex vivo experiments. LL newborns had lower central BAT and skin temperature under thermal neutrality and at 4°C, and higher plasma norepinephrine concentration than LD newborns. In response to 4°C, they had a pronounced decrease in skin temperature and did not increase plasma glycerol. BAT weight in LL newborns was about half of that of LD newborns. Ex vivo, BAT from LL newborns showed increased basal lipolysis and did not respond to NE. In addition, expression of adipogenic/thermogenic genes (UCP1, ADBR3, PPARγ, PPARα, PGC1α, C/EBPβ, and perilipin and of the clock genes Bmal1, Clock and Per2 was increased. Remarkably, the effects observed in LL newborns were absent in LL+Mel newborns. Thus, our results support that maternal melatonin during gestation is important in determining amount and normal functionality of BAT in the neonate.

Seasonal variation in the effect of constant ambient temperature of 24 C in reducing FDG uptake by brown adipose tissue in children