Role of sex hormones in modulation of brown adipose tissue activity

The recent demonstration that metabolically active brown adipose tissue (BAT) is present with a high prevalence in humans undoubtedly represents one of the major advancements in the field of metabolic research in the last few years. The increasing interest in BAT is justified by preclinical observations highlighting an important role of this tissue in energy dissipation and metabolic clearance of substrates from the blood. These findings imply that stimulation of BAT activity may represent a new therapeutic approach for obesity and associated comorbidities. However, before proposing BAT as a target organ for therapeutics in a clinical setting, many further notions about BAT function and modulation need to be explored. Keeping in mind the importance of sex dimorphism in energy metabolism control under physiological and pathological conditions, sex hormones may play a relevant role in the regulation of BAT activity in both males and females. Much of the evidence acquired in the past supports the concept of an important role for different sex hormones in BAT thermogenesis and indicates that this tissue mediates the ability of sex hormones to modulate energy balance. These findings make it plausible that a modified interaction between BAT and sex hormones may contribute to the development and the maintenance of obesity and associated metabolic complications.

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Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk

Frontiers in Endocrinology ◽

10.3389/fendo.2021.652444 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kasiphak Kaikaew ◽

Aldo Grefhorst ◽

Jenny A. Visser

Keyword(s):

Sex Differences ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Sex Hormones ◽

Energy Homeostasis ◽

Overweight And Obesity ◽

The Body ◽

Bat Activity ◽

Pathological Conditions ◽

Brown Adipose

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.

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Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1504239112 ◽

2015 ◽

Vol 112 (21) ◽

pp. 6748-6753 ◽

Cited By ~ 68

Author(s):

Sander Kooijman ◽

Rosa van den Berg ◽

Ashna Ramkisoensing ◽

Mariëtte R. Boon ◽

Eline N. Kuipers ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Intracellular Signaling ◽

Light Exposure ◽

Underlying Mechanism ◽

Circadian Rhythmicity ◽

Day Length ◽

Bat Activity ◽

Brown Adipose ◽

Brown Adipose Tissue Activity

Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity.

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Emerging evidence for the opposite role of circulating irisin levels and brown adipose tissue activity measured by infrared thermography in anthropometric and metabolic profile during childhood

Journal of Thermal Biology ◽

10.1016/j.jtherbio.2021.103010 ◽

2021 ◽

pp. 103010

Author(s):

Franciele De Meneck ◽

Livia Victorino de Souza ◽

Marcos Leal Brioschi ◽

Maria do Carmo Franco

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Infrared Thermography ◽

Metabolic Profile ◽

Brown Adipose ◽

Brown Adipose Tissue Activity

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Abstract 224: Biological Clock Strongly Regulates Brown Adipose Tissue Activity: Implications for Postprandial Triglyceride Metabolism

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.224 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Jimmy Berbée ◽

Rosa van den Berg ◽

Sander Kooijman ◽

Ashna Ramkisoensing ◽

Claudia P Coomans ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Diurnal Rhythm ◽

Biological Clock ◽

Day Length ◽

Time Points ◽

Bat Activity ◽

Brown Adipose ◽

Postprandial Triglyceride ◽

Brown Adipose Tissue Activity

Background: Brown adipose tissue (BAT) is an attractive anti-dyslipidemia target as it burns high amounts of triglycerides (TG) into heat. In humans, plasma TG levels display 24 h variation independent of food intake, indicating a strong regulation by the biological clock. We recently showed that prolonged day length decreases the uptake of TG by BAT. We now aimed to assess the 24 h rhythm of BAT activity, the effect of day length thereon, and the consequences for postprandial TG metabolism. Methods and Results: Male C57Bl/6J mice were exposed to short (8 h), regular (12 h), or long (16 h) days during 5 weeks. The rhythm of BAT was determined by its capacity to take up plasma TG-derived fatty acids (FA) at 6 time points during a 24 h period. Mice exposed to regular days displayed a remarkable diurnal pattern of TG-derived FA uptake from glycerol tri[ 3 H]oleate-labeled VLDL-like particles by BAT, but not by other tissues, reaching a peak [ 3 H]FA uptake at onset of dark. Short day length increased the amplitude of [ 3 H]FA uptake by 3-fold and advanced the peak of [ 3 H]FA uptake, again to onset of dark. Conversely, long day length delayed the peak to onset of dark. We next assessed whether BAT rhythmicity affects postprandial TG clearance in dyslipidemic APOE*3-Leiden.CETP mice. Mice were fed a western-type diet that were exposed to either a short (8 h) or long 16 h (long) days and gavaged with olive oil at several time points during the day. Irrespective of day length, postprandial TG excursion was virtually absent before the onset of dark (highest BAT activity) and high before onset of light (lowest BAT activity). Conclusion: Day length dictates a diurnal rhythm in TG-derived FA uptake capacity of BAT, thereby strongly determining postprandial TG metabolism. We propose that the diurnal variations in TG levels observed in humans may be explained by a diurnal rhythm in BAT activity.

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Novel role of cholesteryl ester transfer protein (CETP): attenuation of adiposity by enhancing lipolysis and brown adipose tissue activity

Metabolism ◽

10.1016/j.metabol.2020.154429 ◽

2021 ◽

Vol 114 ◽

pp. 154429

Author(s):

Helena F. Raposo ◽

Patricia Forsythe ◽

Bruno Chausse ◽

Júlia Z. Castelli ◽

Pedro M. Moraes-Vieira ◽

...

Keyword(s):

Adipose Tissue ◽

Cholesteryl Ester ◽

Brown Adipose Tissue ◽

Cholesteryl Ester Transfer Protein ◽

Transfer Protein ◽

Brown Adipose ◽

Brown Adipose Tissue Activity

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Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function

Journal of Biological Chemistry ◽

10.1074/jbc.m116.728188 ◽

2016 ◽

Vol 291 (33) ◽

pp. 17247-17257 ◽

Cited By ~ 43

Author(s):

Naresh C. Bal ◽

Santosh K. Maurya ◽

Sushant Singh ◽

Xander H. T. Wehrens ◽

Muthu Periasamy

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Skeletal Muscles ◽

Dominant Role ◽

Major Site ◽

Bat Activity ◽

Brown Adipose ◽

A Site

Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides brown adipose tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle-based NST. However, muscle-based NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum Ca2+ cycling and that its regulation by SLN can be the basis for muscle NST. Because of the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study, we investigated whether muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT, which constitutes ∼70% of total BAT) and exposed the mice to prolonged cold (4 °C) for 9 days. The iBAT-ablated mice were able to maintain optimal body temperature (∼35–37 °C) during the entire period of cold exposure. After 4 days in the cold, both sham controls and iBAT-ablated mice stopped shivering and resumed routine physical activity, indicating that they are cold-adapted. The iBAT-ablated mice showed higher oxygen consumption and decreased body weight and fat mass, suggesting an increased energy cost of cold adaptation. The skeletal muscles in these mice underwent extensive remodeling of both the sarcoplasmic reticulum and mitochondria, including alteration in the expression of key components of Ca2+ handling and mitochondrial metabolism. These changes, along with increased sarcolipin expression, provide evidence for the recruitment of NST in skeletal muscle. These studies collectively suggest that skeletal muscle becomes the major site of NST when BAT activity is minimized.

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Mulberry leaf polysaccharides ameliorate obesity through activation of brown adipose tissue and modulation of the gut microbiota in high-fat diet fed mice

Food & Function ◽

10.1039/d1fo02324a ◽

2022 ◽

Author(s):

Ruilin Li ◽

Zihan Xue ◽

Shuqin Li ◽

Jingna Zhou ◽

Junyu Liu ◽

...

Keyword(s):

Adipose Tissue ◽

Gut Microbiota ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Bat Activity ◽

Mulberry Leaf ◽

Brown Adipose ◽

Activity Induction

Mulberry leaf polysaccharides have anti-obesity effects, and their mechanism likely involves an integrated role of white adipose browning, BAT activity induction and gut microbiota modulation.

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Abstract P496: Exosomes From Brown Adipose Tissue Contain Cardiac Gene-regulatory Elements

Circulation Research ◽

10.1161/res.129.suppl_1.p496 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Vikram Shettigar ◽

Sarah Sturgill ◽

Benjamin Hu ◽

Lisa Baer ◽

Carmem Peres Valgas Da Silva ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Heart Function ◽

Regulatory Elements ◽

Bat Activity ◽

Beneficial Effects ◽

Brown Adipose ◽

Cardiac Gene

Exosomes, extracellular vesicles <150 nm, are vehicles for transporting information (i.e., cargo) allowing tissue to tissue communication. Depending on the cargo, exosomes can have beneficial or detrimental effects. Brown Adipose Tissue (BAT) is a thermogenic organ that modulates metabolism. BAT is also an endocrine organ affecting function of various distant tissue. We have recently shown that BAT is an important modulator of the healthy and diseased heart. Adipose tissue is a large source of circulating exosomes, but the effects of BAT and changing BAT activity on circulating exosome number and cargo are unknown. Identifying the role of BAT in modulating exosome number and cargo is important since the myocardium is highly responsive to exosomes. We used various known approaches that increase BAT activity (cold exposure, BATcold) or decrease BAT activity (BAT removal (BATless), obesity (HFD), aging (old)) and examined the number and content of circulating exosomes. Upon BAT activation via cold exposure, there was a large increase in circulating exosome numbers (see figure). All approaches that results in decreased BAT activity resulted in a decrease in circulating exosome numbers (see figure). We further examined the role of changing BAT activity on the content (i.e., cargo) of the exosomes, specifically focusing on miRNA. Interestingly, changing BAT activity resulted in large changes to the content of the exosomes, with some miRNA increasing levels and other miRNA decreasing levels. Some of these identified miRNA have been shown to exert beneficial effects on the heart and many miRNA having no defined effect on cardiac function. We believe that these BAT activated exosomes have the combination and proportion of circulatory miRNA necessary to enhance and maintain heart function. There is a great need for new strategies and approaches for treatment of cardiovascular disease (CVD). Our data suggest that a novel treatment strategy for CVD can be derived from BAT exosomes.

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Differential Role of Adipose Tissues in Obesity and Related Metabolic and Vascular Complications

International Journal of Endocrinology ◽

10.1155/2016/1216783 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 60

Author(s):

Almudena Gómez-Hernández ◽

Nuria Beneit ◽

Sabela Díaz-Castroverde ◽

Óscar Escribano

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Vascular Complications ◽

New Drugs ◽

Adipose Tissues ◽

Brown Adipose ◽

Brown Adipose Tissue Activity ◽

Atherosclerotic Process ◽

New Treatments

This review focuses on the contribution of white, brown, and perivascular adipose tissues to the pathophysiology of obesity and its associated metabolic and vascular complications. Weight gain in obesity generates excess of fat, usually visceral fat, and activates the inflammatory response in the adipocytes and then in other tissues such as liver. Therefore, low systemic inflammation responsible for insulin resistance contributes to atherosclerotic process. Furthermore, an inverse relationship between body mass index and brown adipose tissue activity has been described. For these reasons, in recent years, in order to combat obesity and its related complications, as a complement to conventional treatments, a new insight is focusing on the role of the thermogenic function of brown and perivascular adipose tissues as a promising therapy in humans. These lines of knowledge are focused on the design of new drugs, or other approaches, in order to increase the mass and/or activity of brown adipose tissue or the browning process of beige cells from white adipose tissue. These new treatments may contribute not only to reduce obesity but also to prevent highly prevalent complications such as type 2 diabetes and other vascular alterations, such as hypertension or atherosclerosis.

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