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 Novel Browning Agents, Mechanisms, and Therapeutic Potentials of Brown Adipose Tissue

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Umesh D. Wankhade ◽  
Michael Shen ◽  
Hariom Yadav ◽  
Keshari M. Thakali
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
Brown Adipocytes ◽  
Atp Production ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes

Nonshivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production in order to dissipate energy as heat. Because of its crucial role in regulating energy homeostasis, ongoing exploration of BAT has emphasized its therapeutic potential in addressing the global epidemics of obesity and diabetes. The recent appreciation that adult humans possess functional BAT strengthens this prospect. Furthermore, it has been identified that there are both classical brown adipocytes residing in dedicated BAT depots and “beige” adipocytes residing in white adipose tissue depots that can acquire BAT-like characteristics in response to environmental cues. This review aims to provide a brief overview of BAT research and summarize recent findings concerning the physiological, cellular, and developmental characteristics of brown adipocytes. In addition, some key genetic, molecular, and pharmacologic targets of BAT/Beige cells that have been reported to have therapeutic potential to combat obesity will be discussed.

scholarly journals Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway

2019 ◽  
Vol 11 (9) ◽  
pp. 781-790 ◽  
Author(s):  
Wen Meng ◽  
Xiuci Liang ◽  
Ting Xiao ◽  
Jing Wang ◽  
Jie Wen ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Beige Fat

Abstract Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits. However, the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated. We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis. In the current study, we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat. Fat-specific knockout of Rheb decreased protein kinase A (PKA) activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice. On the other hand, overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes. Mechanistically, Rheb overexpression in brown adipocytes increased Notch expression, leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation. Our study demonstrates that Rheb, by selectively modulating thermogenic gene expression in brown and beige adipose tissues, plays an important role in regulating energy homeostasis.

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 Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation

2014 ◽  
Vol 307 (9) ◽  
pp. E793-E799 ◽  
Author(s):  
G. Andres Contreras ◽  
Yun-Hee Lee ◽  
Emilio P. Mottillo ◽  
James G. Granneman
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Main Site ◽  
Adipose Tissue Depots ◽  
Brown Adipose ◽  
White Fat

Brown adipocytes (BA) generate heat in response to sympathetic activation and are the main site of nonshivering thermogenesis in mammals. Although most BA are located in classic brown adipose tissue depots, BA are also abundant in the inguinal white adipose tissue (iWAT) before weaning. The number of BA is correlated with the density of sympathetic innervation in iWAT; however, the role of continuous sympathetic tone in the establishment and maintenance of BA in WAT has not been investigated. BA marker expression in iWAT was abundant in weaning mice but was greatly reduced by 8 wk of age. Nonetheless, BA phenotype could be rapidly reinstated by acute β3-adrenergic stimulation with CL-316,243 (CL). Genetic tagging of adipocytes with adiponectin-CreERT2 demonstrated that CL reinstates uncoupling protein 1 (UCP1) expression in adipocytes that were present before weaning. Chronic surgical denervation dramatically reduced the ability of CL to induce the expression of UCP1 and other BA markers in the tissue as a whole, and this loss of responsiveness was prevented by concurrent treatment with CL. These results indicate that ongoing sympathetic activity is critical to preserve the ability of iWAT fat cells to express a BA phenotype upon adrenergic stimulation.

scholarly journals Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes

2017 ◽  
Vol 58 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Rose Kohlie ◽  
Nina Perwitz ◽  
Julia Resch ◽  
Sebastian M Schmid ◽  
Hendrik Lehnert ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Cellular Mechanisms ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Mass ◽  
Brown Adipose

Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential, it may dissipate excessive energy, regulate body weight and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT thermogenesis, but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells. D1-like and D2-like receptors were detectable at the protein level. Stimulation with DA caused an increase in cAMP concentrations. Oxygen consumption rates (OCR), mitochondrial membrane potential (Δψm) and uncoupling protein 1 (UCP1) levels increased after 24 h of treatment with either DA or a D1-like specific receptor agonist. A D1-like receptor antagonist abolished the DA-mediated effect on OCR, Δψm and UCP1. DA induced the release of fatty acids, which did not additionally alter DA-mediated increases of OCR. Mitochondrial mass (as determined by (i) CCCP- and oligomycin-mediated effects on OCR and (ii) immunoblot analysis of mitochondrial proteins) also increased within 24 h. This was accompanied by an increase in peroxisome proliferator-activated receptor gamma co-activator 1 alpha protein levels. Also, DA caused an increase in p38 MAPK phosphorylation and pharmacological inhibition of p38 MAPK abolished the DA-mediated effect on Δψm. In summary, our study is the first to reveal direct D1-like receptor and p38 MAPK-mediated increases of thermogenesis and mitochondrial mass in brown adipocytes. These results expand our understanding of catecholaminergic effects on BAT thermogenesis.

scholarly journals White, Brown, Beige/Brite: Different Adipose Cells for Different Functions?

Endocrinology ◽  
2013 ◽  
Vol 154 (9) ◽  
pp. 2992-3000 ◽  
Author(s):  
Marta Giralt ◽  
Francesc Villarroya
Keyword(s):  
Adipose Tissue ◽  
Cell Lineage ◽  
Precursor Cells ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Brown Adipose ◽  
Adult Humans ◽  
Adipocyte Cell ◽  
Adipose Cells

Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis in mammals. Rodent studies indicated that BAT thermogenic activity may protect against obesity. Recent findings using novel radiodiagnosis procedures revealed unanticipated high activity of BAT in adult humans. Moreover, complex processes of cell differentiation leading to the appearance of active brown adipocytes have been recently identified. The brown adipocytes clustered in defined anatomical BAT depots of rodents arise from mesenchymal precursor cells common to the myogenic cell lineage. They are being called “classical” or “developmentally programmed” brown adipocytes. However, brown adipocytes may appear after thermogenic stimuli at anatomical sites corresponding to white adipose tissue (WAT). This process is called the “browning” of WAT. The brown adipocytes appearing in WAT derive from precursor cells different from those in classical BAT and are closer to the white adipocyte cell lineage. The brown adipocytes appearing in WAT are often called “inducible, beige, or brite.” The appearance of these inducible brown adipocytes in WAT may also involve transdifferentiation processes of white-to-brown adipose cells. There is no evidence that the ultimate thermogenic function of the beige/brite adipocytes differs from that of classical brown adipocytes, although some genetic data in rodents suggest a relevant role of the browning process in protection against obesity. Although the activation of classical BAT and the browning process share common mechanisms of induction (eg, noradrenergic-mediated induction by cold), multiple novel adrenergic-independent endocrine factors that activate BAT and the browning of WAT have been identified recently. In adult humans, BAT is mainly composed of beige/brite adipocytes, although recent data indicate the persistence of classical BAT at some anatomical sites. Understanding the biological processes controlling brown adipocyte activity and differentiation could help the design of BAT-focused strategies to increase energy expenditure and fight against obesity.

scholarly journals Recent advances in our understanding of brown and beige adipose tissue: the good fat that keeps you healthy

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1129 ◽  
Author(s):  
Michael E. Symonds ◽  
Peter Aldiss ◽  
Mark Pope ◽  
Helen Budge
Keyword(s):  
Adipose Tissue ◽  
Thermal Environment ◽  
Uncoupling Protein ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Adult Humans ◽  
Beige Fat ◽  
Rapid Generation ◽  
Beige Adipose Tissue ◽  
Shivering Thermogenesis

Brown adipose tissue (BAT) possesses a unique uncoupling protein (UCP1) which, when activated, enables the rapid generation of heat and the oxidation of lipids or glucose or both. It is present in small amounts (~15–350 mL) in adult humans. UCP1 is rapidly activated at birth and is essential in preventing hypothermia in newborns, who rapidly generate large amounts of heat through non-shivering thermogenesis. Since the “re-discovery” of BAT in adult humans about 10 years ago, there has been an exceptional amount of research interest. This has been accompanied by the establishment of beige fat, characterised as discrete areas of UCP1-containing cells dispersed within white adipocytes. Typically, the amount of UCP1 in these depots is around 10% of the amount found in classic BAT. The abundance of brown/beige fat is reduced with obesity, and the challenge is to prevent its loss with ageing or to reactivate existing depots or both. This is difficult, as the current gold standard for assessing BAT function in humans measures radio-labelled glucose uptake in the fasted state and is usually dependent on cold exposure and the same subject can be found to exhibit both positive and negative scans with repeated scanning. Rodent studies have identified multiple pathways that may modulate brown/beige fat function, but their direct relevance to humans is constrained, as these studies typically are undertaken in cool-adapted animals. BAT remains a challenging organ to study in humans and is able to swiftly adapt to changes in the thermal environment and thus enable rapid changes in heat production and glucose oxidation.

scholarly journals Neuronal Modulation of Brown Adipose Activity Through Perturbation of White Adipocyte Lipogenesis

2018 ◽  
Author(s):  
Adilson Guilherme ◽  
David J Pedersen ◽  
Felipe Henriques ◽  
Alexander H. Bedard ◽  
Elizabeth Henchey ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Long Distance ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Brown Adipose ◽  
Beige Adipocytes

ABSTRACTWhite adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of “beige” adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.

scholarly journals Current Progress in Adipose Tissue Biology: Implications in Obesity and Its Comorbidities

2020 ◽  
Vol 12 (2) ◽  
pp. 85-101
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Common Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Brown Adipose ◽  
Key Factor ◽  
Beige Fat

BACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function.CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige.SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic disease

scholarly journals CD137 negatively affects “browning” of white adipose tissue during cold exposure

2020 ◽  
Vol 295 (7) ◽  
pp. 2034-2042 ◽  
Author(s):  
Raj Kamal Srivastava ◽  
Annalena Moliner ◽  
Ee-Soo Lee ◽  
Emily Nickles ◽  
Eunice Sim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Surface Protein ◽  
Negative Regulator ◽  
Subcutaneous White Adipose Tissue ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
A Cell

Prolonged cold exposure stimulates the formation of brownlike adipocytes expressing UCP1 (uncoupling-protein-1) in subcutaneous white adipose tissue which, together with classical brown adipose tissue, contributes to maintaining body temperature in mammals through nonshivering thermogenesis. The mechanisms that regulate the formation of these cells, alternatively called beige or brite adipocytes, are incompletely understood. Here we report that mice lacking CD137, a cell surface protein used in several studies as a marker for beige adipocytes, showed elevated levels of thermogenic markers, including UCP1, increased numbers of beige adipocyte precursors, and expanded UCP1-expressing cell clusters in inguinal white adipose tissue after chronic cold exposure. CD137 knockout mice also showed enhanced cold resistance. These results indicate that CD137 functions as a negative regulator of “browning” in white adipose tissue and call into question the use of this protein as a functional marker for beige adipocytes.

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