scholarly journals SUN-590 27-Hydroxycholesterol Triggers the Whitening of Brown Adipose Tissue

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Arvand Asghari ◽  
Linh Bui ◽  
Robert Stephen ◽  
Michihisa Umetani
Keyword(s):  
Estrogen Receptor ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Vehicle Control ◽  
The Body ◽  
Wild Type ◽  
Brown Adipose

Abstract 27-Hydroxycholesterol (27HC) is the most abundant oxysterol in circulation and metabolized by a P450 enzyme CYP7B1. Its levels closely correspond to those of cholesterol in the body. In addition, previously it was found that 27HC is an endogenous selective estrogen receptor modulator (SERM), which links cholesterol metabolism to estrogen receptor actions (1). Brown adipose tissue (BAT) is the primary source of energy expenditure and energy homeostasis, as well as body temperature maintenance. While previously it was believed that BAT activity is limited to neonates and young children, it is now recognized that BAT is also active in adult humans and its function is impaired by metabolic diseases such as obesity. BAT is also a secretory organ and produces brown adipokines, although the exact function of BAT and adipokines from this tissue in obesity has not been completely understood. Recently, it was reported that 27HC plays an important role in obesity and augments body weight gain in response to a high fat, high cholesterol (HFHC) diet by increasing pre-adipocyte population in the white adipose tissue. 27HC mimics the effects by HFHC diet-feeding on white adipose tissue, such as promoting the inflammation and macrophage infiltration (2). In this study, we explored the effect of 27HC on BAT morphology and function. First, we compared the morphology of BAT from wild-type mice and Cyp7b1-/- mice that have elevated levels of 27HC using H&E staining. Interestingly, brown adipocytes from Cyp7b1-/- mice were larger in cell size than those from wild-type mice, and the cells were mostly unilocular compared to the multilocular cells from wild-type mice, indicating the transition toward a “whitening” phenotype. Next, We treated mice fed a normal chow or a HFHC diet with 27HC or vehicle control for 8 weeks to examine the direct effect by 27HC on BAT. Similar to the phenotype in Cyp7b1-/-mice, 27HC increased the “whitening” of BAT regardless of the diet. We also determined the gene expression of brown adipocyte markers such as UCP1, PGC1a, and DIO2, and found that 27HC significantly decreased the expression of the BAT markers regardless of the diet, confirming the “whitening” observed in the morphology. Moreover, the energy expenditure in mice treated with 27HC was decreased compared to the vehicle control on a HFHC diet, suggesting that 27HC also alters BAT function. These results show that 27HC causes the whitening of BAT, and shed light on the important role of 27HC in brown adipose tissue function. Future experiments will be warranted toward further understanding of the role of 27HC in BAT function. Reference:(1) Umetani, Michihisa, et al. Nature medicine 13.10 (2007): 1185. (2) Asghari, Arvand, et al. Endocrinology 160.10 (2019): 2485-2494.

scholarly journals CD47 differentially regulates white and brown fat function

Biology Open ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. bio056747
Author(s):  
Heather Norman-Burgdolf ◽  
Dong Li ◽  
Patrick Sullivan ◽  
Shuxia Wang
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Brown Fat ◽  
Chow Diet ◽  
Wild Type ◽  
Comparable Amount ◽  
Brown Adipose ◽  
Deficient Mice

ABSTRACTMechanisms that enhance energy expenditure are attractive therapeutic targets for obesity. Previously we have demonstrated that mice lacking cd47 are leaner, exhibit increased energy expenditure, and are protected against diet-induced obesity. In this study, we further defined the physiological role of cd47 deficiency in regulating mitochondrial function and energy expenditure in both white and brown adipose tissue. We observed that cd47 deficient mice (under normal chow diet) had comparable amount of white fat mass but reduced white adipocyte size as compared to wild-type mice. Subsequent ex vivo and in vitro studies suggest enhanced lipolysis, and not impaired lipogenesis or energy utilization, contributes to this phenotype. In contrast to white adipose tissue, there were no obvious morphological differences in brown adipose tissue between wild-type and knockout mice. However, mitochondria isolated from brown fat of cd47 deficient mice had significantly higher rates of free fatty acid-mediated uncoupling. This suggests that enhanced fuel availability via white adipose tissue lipolysis may perpetuate elevated brown adipose tissue energy expenditure and contributes to the lean phenotype observed in cd47 deficient mice.

scholarly journals Genome-Wide Identification and Characterization of Long Noncoding RNAs of Brown to White Adipose Tissue Transformation in Goats

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 904 ◽  
Author(s):  
Linjie Wang ◽  
Xin Yang ◽  
Yuehua Zhu ◽  
Siyuan Zhan ◽  
Zhe Chao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Unsaturated Fatty Acids ◽  
Uncoupling Protein ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Brown Adipose ◽  
Perirenal Fat

Long noncoding RNAs (lncRNAs) play an important role in the thermogenesis and energy storage of brown adipose tissue (BAT). However, knowledge of the cellular transition from BAT to white adipose tissue (WAT) and the potential role of lncRNAs in goat adipose tissue remains largely unknown. In this study, we analyzed the transformation from BAT to WAT using histological and uncoupling protein 1 (UCP1) gene analyses. Brown adipose tissue mainly existed within the goat perirenal fat at 1 day and there was obviously a transition from BAT to WAT from 1 day to 1 year. The RNA libraries constructed from the perirenal adipose tissues of 1 day, 30 days, and 1 year goats were sequenced. A total number of 21,232 lncRNAs from perirenal fat were identified, including 5393 intronic-lncRNAs and 3546 antisense-lncRNAs. Furthermore, a total of 548 differentially expressed lncRNAs were detected across three stages (fold change ≥ 2.0, false discovery rate (FDR) < 0.05), and six lncRNAs were validated by qPCR. Furthermore, trans analysis found lncRNAs that were transcribed close to 890 protein-coding genes. Additionally, a coexpression network suggested that 4519 lncRNAs and 5212 mRNAs were potentially in trans-regulatory relationships (r > 0.95 or r < −0.95). In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the targeted genes were involved in the biosynthesis of unsaturated fatty acids, fatty acid elongation and metabolism, the citrate cycle, oxidative phosphorylation, the mitochondrial respiratory chain complex, and AMP-activated protein kinase (AMPK) signaling pathways. The present study provides a comprehensive catalog of lncRNAs involved in the transformation from BAT to WAT and provides insight into understanding the role of lncRNAs in goat brown adipogenesis.

scholarly journals Chrysanthemum Leaf Ethanol Extract Prevents Obesity and Metabolic Disease in Diet-Induced Obese Mice via Lipid Mobilization in White Adipose Tissue

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1347 ◽  
Author(s):  
Ri Ryu ◽  
Eun-Young Kwon ◽  
Ji-Young Choi ◽  
Jong Cheol Shon ◽  
Kwang-Hyeon Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
Ethanol Extract ◽  
The Body ◽  
Obese Mice ◽  
Peripheral Tissues ◽  
Lipid Mobilization ◽  
Obesity And Diabetes ◽  
Brown Adipose

This study aimed to elucidate the molecular mechanism of Chrysanthemum morifolium Ramat. against obesity and diabetes, by comparing the transcriptional changes in epididymal white adipose tissue (eWAT) with those of the bioactive compound in C. morifolium, luteolin (LU). Male C57BL/6J mice were fed a normal diet, high-fat diet (HFD), and HFD supplemented with 1.5% w/w chrysanthemum leaf ethanol extract (CLE) for 16 weeks. Supplementation with CLE and LU significantly decreased the body weight gain and eWAT weight by stimulating mRNA expressions for thermogenesis and energy expenditure in eWAT via lipid mobilization, which may be linked to the attenuation of dyslipidemia. Furthermore, CLE and LU increased uncoupling protein-1 protein expression in brown adipose tissue, leading to energy expenditure. Of note, CLE and LU supplements enhanced the balance between lipid storage and mobilization in white adipose tissue (WAT), in turn, inhibiting adipocyte inflammation and lipotoxicity of peripheral tissues. Moreover, CLE and LU attenuated hepatic steatosis by suppressing hepatic lipogenesis, thereby ameliorating insulin resistance and dyslipidemia. Our data suggest that CLE helps inhibit obesity and its comorbidities via the complex interplay between liver and WAT in diet-induced obese mice.

scholarly journals Direct Delivery of Metformin to Subcutaneous White Adipose Tissue and Brown Adipose Tissue for Combating Obesity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1603-1603
Author(s):  
Mehrnaz Abbasi ◽  
Shu Wang
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Time Course ◽  
Direct Injection ◽  
Area Under The Curve ◽  
P Value ◽  
Brown Adipose ◽  
Direct Delivery

Abstract Objectives Obesity and its comorbidities are major public health problems worldwide. The transformation of white adipose tissue (WAT) to brown adipose tissue (BAT); browning of WAT, may serve as a promising strategy for combating obesity. Metformin is not only the first line of drug for type 2 diabetes but also has an anti-obesity potential. Emerging evidence suggests that metformin can reduce body weight and enhance energy expenditure via activating BAT or browning of WAT. However, metformin delivery to adipose tissue is limited due to the lack of adipocyte-specific surface markers. Thus, the direct injection might be an alternative. Methods ApoE3-Leiden.human cholesteryl ester transfer protein (E3L.CETP) mice (5 mice/group) were fed a high-fat diet (HFD) for 15 weeks. From week 10 to 15, mice were randomly divided into 3 groups as 1. Metformin inguinal WAT (IgWAT) injection, 2. Metformin delivery to interscapular BAT (IBAT) and 3. Saline IgWAT injection (HFD control). Mice received injections twice per week (40 mg/kg/week). Bodyweight (BW), body composition, food intake, energy expenditure and glucose tolerance test (GTT) were measured. Gene expression of beige or brown makers was analyzed using real time-PCR. Results Compared to HFD control mice, IgWAT- and IBAT-treated mice lost 2.16% and 1.9% more of their body fat, respectively (P-value &lt; 0.001). IgWAT- and IBAT-treated mice had 1.09- and 1.24-fold lower area under the curve calculated from the GTT time course than HFD control mice, respectively, but the differences were not statistically significant. The metabolic cage data indicated that both IgWAT- and IBAT-treated mice compared to HFD control mice had significantly decreased respiration exchange ratio (RER) (P &lt; 0.0001). IgWAT-treated mice had significantly lower IgWAT weight than the HFD control mice (P &lt; 0.05). IgWAT-treated compared to HFD control mice had 1.5-, 2-, 2.7- and 3-fold higher expression of UCP1, PRDM16, TMEM26 and Elovl3 in IgWAT, respectively. Conclusions This study demonstrated that local delivery of metformin to IgWAT and IBAT decreased BW and fat mass, which were associated with reduced RER and improved glucose homeostasis. Direct delivery of metformin to IgWAT and IBAT might be an efficient approach for combating obesity via inducing IgWAT browning and enhancing IBAT activity. Funding Sources NIH 1R15AT010395 and AHA 19AIREA34480011.

scholarly journals White, beige and brown adipose tissue: structure, function, specific features and possibility formation and divergence in pigs

2021 ◽  
pp. 10-18
Author(s):  
Irina Chernukha ◽  
Liliya Fedulova ◽  
Elena Kotenkova
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
The Body ◽  
Intermediate Form ◽  
Swine Industry ◽  
Brown Adipose ◽  
Beige Fat ◽  
White Fat ◽  
The Impact

Introduction. Traditionally, mammalian adipose tissue is divided into white (white adipose tissue – WAT) and brown (brown adipose tissue – BAT). While the functions of WAT are well known as the triglyceride depot, the role of BAT in mammalian physiology has been under close investigation. The first description of the role of BAT in maintaining thermogenesis dates back to 1961. This article offers a review of structural and functional specificity of white, beige and brown adipose tissue. Results and discussion. The differences and descriptions of adipocytes and their impact on the maintenance of the main functions of the mammalian body are described in this manuscript. In particular, thermogenesis, stress response, obesity, type II diabetes. In addition to WAT and BAT, an intermediate form was also detected in the body – beige fat (BeAT or Brite). The opposite opinions regarding the presence of three types of adipose tissue in the human and animal bodies are presented. Studies on the identification of uncoupling proteins 1 and 3 and their role in the transformation of white fat into beige/brown are considered. Basically, the data on the factors of endogenous and exogenous nature on their formation are given on the example of the human body. Conclusion. With an abundance of publications on the keywords: “white, brown fat”, these studies, in the overwhelming majority, are devoted to the role of these fats in the formation of human thermogenesis, the assessment of the impact on obesity. Pigs have also been suggested to lack functional BAT, which is a major cause of neonatal death in the swine industry, therefore the focus on investigating role of different types of adipose tissue in pigs seems very promising in order to understand whether there is a compensating mechanism of thermogenesis.

scholarly journals Insulin sensing by astrocytes is critical for normal thermogenesis and body temperature regulation

2020 ◽  
Vol 247 (1) ◽  
pp. 39-52
Author(s):  
Iyad H Manaserh ◽  
Emily Maly ◽  
Marziyeh Jahromi ◽  
Lakshmikanth Chikkamenahalli ◽  
Joshua Park ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Insulin Signaling ◽  
Insulin Receptors ◽  
Metabolic Dysregulation ◽  
Brown Adipose ◽  
Novel Target

The important role of astrocytes in the central control of energy balance and glucose homeostasis has recently been recognized. Changes in thermoregulation can lead to metabolic dysregulation, but the role of astrocytes in this process is not yet clear. Therefore, we generated mice congenitally lacking insulin receptors (Ir) in astrocytes (IrKOGFAP mice) to investigate the involvement of astrocyte insulin signaling. IrKOGFAP mice displayed significantly lower energy expenditure and a strikingly lower basal and fasting body temperature. When exposed to cold, however, they were able to mount a thermogenic response. IrKOGFAP mice displayed sex differences in metabolic function and thermogenesis that may contribute to the development of obesity and type II diabetes as early as 2 months of age. While brown adipose tissue exhibited higher adipocyte size in both sexes, more apoptosis was seen in IrKOGFAP males. Less innervation and lower BAR3 expression levels were also observed in IrKOGFAP brown adipose tissue. These effects have not been reported in models of astrocyte Ir deletion in adulthood. In contrast, body weight and glucose regulatory defects phenocopied such models. These findings identify a novel role for astrocyte insulin signaling in the development of normal body temperature control and sympathetic activation of BAT. Targeting insulin signaling in astrocytes has the potential to serve as a novel target for increasing energy expenditure.

scholarly journals Vibration Training Triggers Brown Adipocyte Relative Protein Expression in Rat White Adipose Tissue

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Sun ◽  
Ruixia Zeng ◽  
Ge Cao ◽  
Zhibang Song ◽  
Yibo Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Protein Level ◽  
The Body ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Vibration Training ◽  
Novel Strategy

Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear. In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks. We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group(n=6). Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 in BAT. Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 and inflammatory relative proteins, IL-6 and TNFα. Simultaneously, ATP content and PPARγprotein level in WAT became less in rats compared with nonvibration group. The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve.

scholarly journals Leptin: Is It Thermogenic?

2019 ◽  
Vol 41 (2) ◽  
pp. 232-260 ◽  
Author(s):  
Alexander W Fischer ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Sympathetic Nerve Activity ◽  
Leptin Receptor ◽  
The Body ◽  
Nerve Activity ◽  
Brown Adipose ◽  
Intact Organism

Abstract Animals that lack the hormone leptin become grossly obese, purportedly for 2 reasons: increased food intake and decreased energy expenditure (thermogenesis). This review examines the experimental evidence for the thermogenesis component. Analysis of the data available led us to conclude that the reports indicating hypometabolism in the leptin-deficient ob/ob mice (as well as in the leptin-receptor-deficient db/db mice and fa/fa rats) derive from a misleading calculation artefact resulting from expression of energy expenditure per gram of body weight and not per intact organism. Correspondingly, the body weight-reducing effects of leptin are not augmented by enhanced thermogenesis. Congruent with this, there is no evidence that the ob/ob mouse demonstrates atrophied brown adipose tissue or diminished levels of total UCP1 mRNA or protein when the ob mutation is studied on the inbred C57BL/6 mouse background, but a reduced sympathetic nerve activity is observed. On the outbred “Aston” mouse background, brown adipose tissue atrophy is seen, but whether this is of quantitative significance for the development of obesity has not been demonstrated. We conclude that leptin is not a thermogenic hormone. Rather, leptin has effects on body temperature regulation, by opposing torpor bouts and by shifting thermoregulatory thresholds. The central pathways behind these effects are largely unexplored.

Evidence against a Mediatory Role of Brown Adipose Tissue in the Calorigenic Response of Cold-Acclimated Rats to Noradrenaline

1974 ◽  
Vol 52 (6) ◽  
pp. 1051-1062 ◽  
Author(s):  
David O. Foster
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
The Body ◽  
Albino Rats ◽  
Interscapular Brown Adipose Tissue ◽  
Unique Role ◽  
Brown Adipose ◽  
Colonic Temperature ◽  
Vascular Connections

The calorigenic response to infused noradrenaline (NA) of barbital-anesthetized, cold-acclimated, adult, gnotobiotic, albino rats tested 1 h after removal of interscapular brown adipose tissue (I.B.A.T.) was 14% lower than before surgery and 15% lower than the response of either sham-operated or non-operated rats; but 4 days later, the response of rats without I.B.A.T. was not significantly different from that of the controls. In unanesthetized rats, response to NA was also unaffected by interruption of blood flow to I.B.A.T. 1–3 days before the measurements. Since these results do not conform with previous findings of 30–60% reductions in response to NA following removal of I.B.A.T. or interference with the tissue's vascular connections, they contradict the current hypothesis that the B.A.T. of cold-acclimated rodents has a unique role as a mediator of calorigenesis in other tissues.A supplementary feature of the study was the discovery of apparent thermolability in the process by which cold-acclimated rats respond calorigenically to NA. If, during infusion of NA, colonic temperature exceeded about 41.5 °C, an apparently critical degree of hyperthermia response to the hormone during a subsequent infusion was reduced. This reduction was linearly related to the previous maximum colonic temperature over the range 41.6–42.4 °C and amounted to approximately 70% at 42.4 °C. These results indicate the necessity for monitoring the body temperatures of animals during infusion of NA, particularly in experiments in which two or more tests of response to NA are done on the same animal. Since such temperature measurements were not reported in those studies that have suggested a mediatory role of B.A.T. in calorigenesis in rodents, it is not possible to resolve the discrepancies on this basis.

scholarly journals Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review

2021 ◽  
Vol 15 ◽  
Author(s):  
Lachlan Van Schaik ◽  
Christine Kettle ◽  
Rodney Green ◽  
Helen R. Irving ◽  
Joseph A. Rathner
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Energy Utilization ◽  
Therapeutic Effects ◽  
Exciting Field ◽  
Brown Adipose ◽  
The Impact

The impact of brown adipose tissue (BAT) metabolism on understanding energy balance in humans is a relatively new and exciting field of research. The pathogenesis of obesity can be largely explained by an imbalance between caloric intake and energy expenditure, but the underlying mechanisms are far more complex. Traditional non-selective sympathetic activators have been used to artificially elevate energy utilization, or suppress appetite, however undesirable side effects are apparent with the use of these pharmacological interventions. Understanding the role of BAT, in relation to human energy homeostasis has the potential to dramatically offset the energy imbalance associated with obesity. This review discusses paradoxical effects of caffeine on peripheral adenosine receptors and the possible role of adenosine in increasing metabolism is highlighted, with consideration to the potential of central rather than peripheral mechanisms for caffeine mediated BAT thermogenesis and energy expenditure. Research on the complex physiology of adipose tissue, the embryonic lineage and function of the different types of adipocytes is summarized. In addition, the effect of BAT on overall human metabolism and the extent of the associated increase in energy expenditure are discussed. The controversy surrounding the primary β-adrenoceptor involved in human BAT activation is examined, and suggestions as to the lack of translational findings from animal to human physiology and human in vitro to in vivo models are provided. This review compares and distinguishes human and rodent BAT effects, thus developing an understanding of human BAT thermogenesis to aid lifestyle interventions targeting obesity and metabolic syndrome. The focus of this review is on the effect of BAT thermogenesis on overall metabolism, and the potential therapeutic effects of caffeine in increasing metabolism via its effects on BAT.

Sign in / Sign up

Export Citation Format

Share Document