scholarly journals Adipose tissue browning in mice and humans

2019 ◽  
Vol 241 (3) ◽  
pp. R97-R109 ◽  
Author(s):  
Carsten T Herz ◽  
Florian W Kiefer
Keyword(s):  
Adipose Tissue ◽  
Therapeutic Implications ◽  
Obesity Epidemic ◽  
Fat Depots ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Metabolic Properties ◽  
Thermogenic Adipocytes ◽  
Tissue Browning

In the midst of an obesity epidemic, the promotion of brown adipose tissue (BAT) function and the browning of white adipose tissue (WAT) have emerged as promising therapeutic targets to increase energy expenditure and counteract weight gain. Despite the fact that the thermogenic potential of bone fide BAT in rodents is several orders of magnitudes higher than white fat containing brite/beige adipocytes, WAT browning represents a particularly intriguing concept in humans given the extreme amount of excess WAT in obese individuals. In addition, the clear distinction between classic brown and beige fat that has been proposed in mice does not exist in humans. In fact, studies of human BAT biopsies found controversial results suggesting both classic brown and beige characteristics. Irrespective of the true ‘color’, accumulating evidence suggests the induction of thermogenic adipocytes in human WAT depots in response to specific stimuli, highlighting that WAT browning may occur in both, mice and humans. These observations also emphasize the great plasticity of human fat depots and raise important questions about the metabolic properties of thermogenically active adipose tissue in humans and the potential therapeutic implications. We will first review the cellular and molecular aspects of selected adipose tissue browning concepts that have been identified in mouse models with emphasis on neuronal factors, the microbiome, immune cells and several hormones. We will also summarize the evidence for adipose tissue browning in humans including some experimental pharmacologic approaches.

scholarly journals Multifaceted Roles of Beige Fat in Energy Homeostasis Beyond UCP1

Endocrinology ◽  
2018 ◽  
Vol 159 (7) ◽  
pp. 2545-2553 ◽  
Author(s):  
Carlos Henrique Sponton ◽  
Shingo Kajimura
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Developmental Regulation ◽  
Brown Adipocytes ◽  
Adipose Tissue Depots ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Adipose Cells

Abstract Beige adipocytes are an inducible form of thermogenic adipose cells that emerge within the white adipose tissue in response to a variety of environmental stimuli, such as chronic cold acclimation. Similar to brown adipocytes that reside in brown adipose tissue depots, beige adipocytes are also thermogenic; however, beige adipocytes possess unique, distinguishing characteristics in their developmental regulation and biological function. This review highlights recent advances in our understanding of beige adipocytes, focusing on the diverse roles of beige fat in the regulation of energy homeostasis that are independent of the canonical thermogenic pathway via uncoupling protein 1.

scholarly journals Brown and Beige Fat: Therapeutic Potential in Obesity

2014 ◽  
Vol 6 (2) ◽  
pp. 65
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Therapeutic Effects ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Adipose Organ

BACKGROUND: The epidemic of obesity and type 2 diabetes presents a serious challenge to scientific and biomedical communities worldwide. There has been an upsurge of interest in the adipocyte coincident with the onset of the obesity epidemic and the realization that adipose tissue plays a major role in the regulation of metabolic function.CONTENT: Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible ‘brown-like’ adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.SUMMARY: The complexity of adipose tissue presents numerous challenges but also several opportunities for therapeutic intervention. There is persuasive evidence from animal models that enhancement of the function of brown adipocytes, beige adipocytes or both in humans could be very effective for treating type 2 diabetes and obesity. Moreover, there are now an extensive variety of factors and pathways that could potentially be targeted for therapeutic effects. In particular, the discoveries of circulating factors, such as irisin, fibroblast growth factor (FGF)21 and natriuretic peptides, that enhance brown and beige fat function in mice have garnered tremendous interest. Certainly, the next decade will see massive efforts to use beige and brown fat to ameliorate human metabolic disease.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, adipose organ, thermogenesis, energy expenditure

scholarly journals miR17-92 cluster drives white adipose tissue browning

2020 ◽  
Vol 65 (3) ◽  
pp. 97-107
Author(s):  
Yuanyuan Huang ◽  
Hanlin Zhang ◽  
Meng Dong ◽  
Lei Zhang ◽  
Jun Lin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Critical Role ◽  
Beneficial Effects ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
And Function ◽  
White Fat

White adipose tissue (WAT) browning may have beneficial effects for treating metabolic syndrome. miRNA are important regulators of the differentiation, development, and function of brown and beige adipocytes. Here, we found that the cold-inducible miRNA17-92 cluster is enriched in brown adipose tissue (BAT) compared with WAT. Overexpression of the miR17-92 cluster in C3H10T1/2 cells, a mouse mesenchymal stem cell line, enhanced the thermogenic capacity of adipocytes. Furthermore, we observed a significant reduction in adiposity in adipose tissue-specific miR17-92 cluster transgenic (TG) mice. This finding is partly explained by dramatic increases in white fat browning and energy expenditure. Interestingly, the miR17-92 cluster stimulated WAT browning without altering BAT activity in mice. In addition, when we removed the intrascapular BAT (iBAT), the TG mice could maintain their body temperature well under cold exposure. At the molecular level, we found that the miR17-92 cluster targets Rb1, a beige cell repressor in WAT. The present study reveals a critical role for the miR17-92 cluster in regulating WAT browning. These results may be helpful for better understanding the function of beige fat, which could compensate for the lack of BAT in humans, and may open new avenues for combatting metabolic syndrome.

scholarly journals Adipose tissue growth and development: the modulating role of ambient temperature

2021 ◽  
Vol 248 (1) ◽  
pp. R19-R28
Author(s):  
Michael E Symonds ◽  
Mark Pope ◽  
Ian Bloor ◽  
James Law ◽  
Reham Alagal ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ambient Temperature ◽  
Uncoupling Protein ◽  
Tissue Growth ◽  
Long Term Effects ◽  
Mitochondrial Uncoupling ◽  
Fat Depots ◽  
Brown Adipose ◽  
Beige Fat ◽  
And Function

Adipose tissue is usually laid down in small amounts in the foetus and is characterised as possessing small amounts of the brown adipose tissue-specific mitochondrial uncoupling protein (UCP)1. In adults, a primary factor determining the abundance and function of UCP1 is ambient temperature. Cold exposure causes activation and the rapid generation of heat through the free flow of protons across the mitochondria with no requirement to convert ADP to ATP. In rodents, housing at an ambient temperature below thermoneutrality promotes the appearance of beige like adipocytes. These arise as discrete regions of UCP1 containing cells in white fat depots. There is increasing evidence to show that to gain credible translational results on brown and beige fat function in rodent models that they should be housed at thermoneutrality. This not only reflects the type of environment in which humans spend a majority of their time, but is in accord with the rise of global temperature caused by industrialisation and the uncontrolled burning of fossil fuels. There is now good evidence in adult humans, that stimulating brown fat can improve glucose homeostasis which can be achieved either by nutritional or pharmacological interventions. The challenge, therefore, is to establish credible developmental models in animals maintained at thermoneutrality which will elucidate the true impact of nutrition. The primary focus should fall specifically on the components of breast milk and how these modulate long term effects on brown or beige fat development and function.

scholarly journals Developmental and functional heterogeneity of thermogenic adipose tissue

2020 ◽  
Author(s):  
Hai-Bin Ruan
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Functional Heterogeneity ◽  
Cellular Mechanisms ◽  
Obesity Epidemic ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Branched Chain ◽  
Global Health Challenge

Abstract The obesity epidemic continues to rise as a global health challenge. Thermogenic brown and beige adipocytes dissipate chemical energy as heat, providing an opportunity for developing new therapeutics for obesity and related metabolic diseases. Anatomically, brown adipose tissue is distributed as discrete depots, while beige adipocytes exist within certain depots of white adipose tissue. Developmentally, brown and beige adipocytes arise from multiple embryonic progenitor populations that are distinct and overlapping. Functionally, they respond to a plethora of stimuli to engage uncoupling protein 1-dependent and independent thermogenic programs, thus improving systemic glucose homeostasis, lipid metabolism, and the clearance of branched-chain amino acids. In this review, we highlight recent advances in our understanding of the molecular and cellular mechanisms that contribute to the developmental and functional heterogeneity of thermogenic adipose tissue.

scholarly journals Inducible Brown Adipose Tissue, or Beige Fat, Is Anabolic for the Skeleton

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2687-2701 ◽  
Author(s):  
Sima Rahman ◽  
Yalin Lu ◽  
Piotr J. Czernik ◽  
Clifford J. Rosen ◽  
Sven Enerback ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Integration Site ◽  
Osteoblastic Activity ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
High Bone

Abstract It is known that insulin resistance and type 2 diabetes mellitus are associated with increased fractures and that brown adipose tissue (BAT) counteracts many if not all of the symptoms associated with type 2 diabetes. By the use of FoxC2AD+/Tg mice, a well-established model for induction of BAT, or beige fat, we present data extending the beneficial action of beige fat to also include a positive effect on bone. FoxC2AD+/Tg mice are lean and insulin-sensitive and have high bone mass due to increased bone formation associated with high bone turnover. Inducible BAT is linked to activation of endosteal osteoblasts whereas osteocytes have decreased expression of the Sost transcript encoding sclerostin and elevated expression of Rankl. Conditioned media (CM) collected from forkhead box c2 (FOXC2)-induced beige adipocytes activated the osteoblast phenotype and increased levels of phospho-AKT and β-catenin in recipient cells. In osteocytes, the same media decreased Sost expression. Immunodepletion of CM with antibodies against wingless related MMTV integration site 10b (WNT10b) and insulin-like growth factor binding protein 2 (IGFBP2) resulted in the loss of pro-osteoblastic activity, and the loss of increase in the levels of phospho-AKT and β-catenin. Conversely, CM derived from cells overexpressing IGFBP2 or WNT10b restored osteoblastic activity in recipient cells. In conclusion, beige fat secretes endocrine/paracrine activity that is beneficial for the skeleton.

scholarly journals Adipose and skeletal muscle thermogenesis: studies from large animals

2018 ◽  
Vol 237 (3) ◽  
pp. R99-R115 ◽  
Author(s):  
John-Paul Fuller-Jackson ◽  
Belinda A Henry
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Heat Dissipation ◽  
Uncoupling Protein ◽  
Calcium Cycling ◽  
Fat Depots ◽  
Brown Adipose ◽  
Beige Adipocytes

The balance between energy intake and energy expenditure establishes and preserves a ‘set-point’ body weight. The latter is comprised of three major components including metabolic rate, physical activity and thermogenesis. Thermogenesis is defined as the cellular dissipation of energy via heat production. This process has been extensively characterised in brown adipose tissue (BAT), wherein uncoupling protein 1 (UCP1) creates a proton leak across the inner mitochondrial membrane, diverting protons away from ATP synthesis and resulting in heat dissipation. In beige adipocytes and skeletal muscle, thermogenesis can occur independent of UCP1. Beige adipocytes have been shown to produce heat via UCP1 as well as via both futile creatine and calcium cycling pathways. On the other hand, the UCP1 homologue UCP3 is abundant in skeletal muscle and post-prandial thermogenesis has been associated with UCP3 and the futile calcium cycling. This review will focus on the differential contributions of adipose tissue and skeletal muscle in determining total thermogenic output and energy expenditure in large mammals. Sheep and pigs do not have a circumscribed brown fat depot but rather possess white fat depots that contain brown and beige adipocytes interspersed amongst white adipose tissue. This is representative of humans, where brown, beige and white adipocytes have been identified in the neck and supraclavicular regions. This review will describe the mechanisms of thermogenesis in pigs and sheep and the relative roles of skeletal muscle and adipose tissue thermogenesis in controlling body weight in larger mammals.

scholarly journals Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Fernando Lizcano ◽  
Diana Vargas
Keyword(s):  
Adipose Tissue ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Beige Adipocyte ◽  
Fat Depots ◽  
Physiological Capacity ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes

All mammals own two main forms of fat. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat. Since adult humans possess significant amounts of active brown fat depots and their mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate itself from white adipocytes. Importantly, adult human brown adipocyte appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases. Because many epigenetic changes can affect beige adipocyte differentiation, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important for therapeutic strategies. In this review we discuss some recent observations arising from the great physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.

scholarly journals The significance of beige and brown fat in humans

2017 ◽  
Vol 6 (5) ◽  
pp. R70-R79 ◽  
Author(s):  
Florian W Kiefer
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Brown Fat ◽  
Therapeutic Concept ◽  
Bat Activity ◽  
Fat Depots ◽  
Brown Adipose ◽  
Beige Adipocytes

Promotion of brown adipose tissue (BAT) activity or browning of white adipose tissue has shown great potential as anti-obesity strategy in numerous preclinical models. The discovery of active BAT in humans and the recent advances in the understanding of human BAT biology and function have significantly propelled this field of research. Pharmacological stimulation of energy expenditure to counteract obesity has always been an intriguing therapeutic concept; with the identification of the specific molecular pathways of brown fat function, this idea has now become as realistic as ever. Two distinct strategies are currently being pursued; one is the activation of bone fide BAT, the other is the induction of BAT-like cells or beige adipocytes within white fat depots, a process called browning. Recent evidence suggests that both phenomena can occur in humans. Cold-induced promotion of BAT activity is strongly associated with enhanced thermogenesis and energy expenditure in humans and has beneficial effects on fat mass and glucose metabolism. Despite these encouraging results, a number of issues deserve additional attention including the distinct characteristics of human vs rodent BAT, the heterogeneity of human BAT depots or the identification of the adipocyte precursors that can give rise to thermogenic cells in human adipose tissue. In addition, many pharmaceutical compounds are being tested for their ability to promote a thermogenic program in human adipocytes. This review summarizes the current knowledge about the various cellular and molecular aspects of human BAT as well as the relevance for energy metabolism including its therapeutic potential for obesity.

scholarly journals Transcription Regulators and Hormones Involved in the Development of Brown Fat and White Fat Browning: Transcriptional and Hormonal Control of Brown/Beige Fat Development

2018 ◽  
pp. 347-362 ◽  
Author(s):  
J. ZHANG ◽  
H. WU ◽  
S. MA ◽  
F. JING ◽  
C. YU ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hormonal Control ◽  
Brown Fat ◽  
Metabolic Complications ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
New Strategy ◽  
Beige Fat ◽  
White Fat

The high prevalence of obesity and related metabolic complications has inspired research on adipose tissues. Three kinds of adipose tissues are identified in mammals: brown adipose tissue (BAT), beige or brite adipose tissue and white adipose tissue (WAT). Beige adipocytes share some characteristics with brown adipocytes such as the expression of UCP1. Beige adipocytes can be activated by environmental stimuli or pharmacological treatment, and this change is accompanied by an increase in energy consumption. This process is called white browning, and it facilitates the maintenance of a lean and healthy phenotype. Thus, promoting beige adipocyte development in WAT shows promise as a new strategy in treating obesity and related metabolic consequences. In this review, we summarized the current understanding of the regulators and hormones that participate in the development of brown fat and white fat browning.

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