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.

Sympathetic Innervation of White Adipose Tissue: to Beige or Not to Beige?

Physiology ◽  
2021 ◽  
Vol 36 (4) ◽  
pp. 246-255
Author(s):  
Heike Münzberg ◽  
Elizabeth Floyd ◽  
Ji Suk Chang
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Metabolic Regulation ◽  
Current Knowledge ◽  
Sympathetic Innervation ◽  
Neuronal Circuits ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Obesity Research ◽  
Neuronal Regulation

Obesity research progresses in understanding neuronal circuits and adipocyte biology to regulate metabolism. However, the interface of neuro-adipocyte interaction is less studied. We summarize the current knowledge of adipose tissue innervation and interaction with adipocytes and emphasize adipocyte transitions from white to brown adipocytes and vice versa. We further highlight emerging concepts for the differential neuronal regulation of brown/beige versus white adipocyte and the interdependence of both for metabolic regulation.

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 Interscapular brown adipose tissue denervation does not promote the oxidative activity of inguinal white adipose tissue in male mice

2018 ◽  
Vol 315 (5) ◽  
pp. E815-E824 ◽  
Author(s):  
Sébastien M. Labbé ◽  
Alexandre Caron ◽  
William T. Festuccia ◽  
Roger Lecomte ◽  
Denis Richard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Oxidative Activity ◽  
Substrate Uptake ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Apparent Lack ◽  
Brown Adipose

Brown adipose tissue (BAT) thermogenesis is a key controller of energy metabolism. In response to cold or other adrenergic stimuli, brown adipocytes increase their substrate uptake and oxidative activity while uncoupling ATP synthesis from the mitochondrial respiratory chain activity. Brown adipocytes are found in classic depots such as in the interscapular BAT (iBAT). They can also develop in white adipose tissue (WAT), such as in the inguinal WAT (iWAT), where their presence has been associated with metabolic improvements. We previously reported that the induction of oxidative metabolism in iWAT is low compared with that of iBAT, even after sustained adrenergic stimulation. One explanation to this apparent lack of thermogenic ability of iWAT is the presence of an active iBAT, which may prevent the full activation of iWAT. In this study, we evaluated whether iBAT denervation-induced browning of white fat enhanced the thermogenic activity of iWAT following cold acclimation, under beta-3 adrenergic stimulation (CL 316,243). Following a bilateral denervation of iBAT, we assessed energy balance, evaluated the oxidative activity of iBAT and iWAT using 11C-acetate, and quantified the dynamic glucose uptake of those tissues using 2-deoxy-2-[18F]- fluoro-d-glucose. Our results indicate that despite portraying marked browning and mildly enhanced glucose uptake, iWAT of cold-adapted mice does not exhibit significant oxidative activity following beta-3 adrenergic stimulation in the absence of a functional iBAT. The present results suggest that iWAT is not readily recruitable as a thermogenic organ even when functional iBAT is lacking.

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.

Novel Aspects of White Adipose Tissue Browning by Thyroid Hormones

2019 ◽  
Vol 128 (06/07) ◽  
pp. 446-449 ◽  
Author(s):  
Kerstin Krause
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormones ◽  
White Adipose Tissue ◽  
Brown Adipocytes ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
Tissue Browning ◽  
Thermogenic Capacity ◽  
Thermogenic Response

AbstractThyroid hormones are essential for the full thermogenic capacity of brown adipose tissue. The thermogenic response of brown adipocytes to thyroid hormones is resulting from the synergistic interaction of thyroid hormones with the sympathetic nervous system. In recent years, evidence has been provided that thyroid hormones also induce the browning of white adipose tissues. This review will provide a brief overview about the recent findings regarding the effects of thyroid hormones on adipose tissue thermogenesis including central and peripheral regulation of white adipose tissue browning.

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.

scholarly journals Epigenetic Regulators of White Adipocyte Browning

Epigenomes ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 3
Author(s):  
Ravikanth Nanduri
Keyword(s):  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
White Adipocyte ◽  
Primary Function ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Epigenetic Regulators

Adipocytes play an essential role in maintaining energy homeostasis in mammals. The primary function of white adipose tissue (WAT) is to store energy; for brown adipose tissue (BAT), primary function is to release fats in the form of heat. Dysfunctional or excess WAT can induce metabolic disorders such as dyslipidemia, obesity, and diabetes. Preadipocytes or adipocytes from WAT possess sufficient plasticity as they can transdifferentiate into brown-like beige adipocytes. Studies in both humans and rodents showed that brown and beige adipocytes could improve metabolic health and protect from metabolic disorders. Brown fat requires activation via exposure to cold or β-adrenergic receptor (β-AR) agonists to protect from hypothermia. Considering the fact that the usage of β-AR agonists is still in question with their associated side effects, selective induction of WAT browning is therapeutically important instead of activating of BAT. Hence, a better understanding of the molecular mechanisms governing white adipocyte browning is vital. At the same time, it is also essential to understand the factors that define white adipocyte identity and inhibit white adipocyte browning. This literature review is a comprehensive and focused update on the epigenetic regulators crucial for differentiation and browning of white adipocytes.

Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization

1992 ◽  
Vol 103 (4) ◽  
pp. 931-942 ◽  
Author(s):  
B. Cousin ◽  
S. Cinti ◽  
M. Morroni ◽  
S. Raimbault ◽  
D. Ricquier ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Blot Hybridization ◽  
Morphological Characterization ◽  
Northern Blot Hybridization ◽  
Mitochondrial Uncoupling ◽  
Brown Adipocytes ◽  
Morphological Studies ◽  
Brown Adipose

Brown adipocytes are thermogenic cells which play an important role in energy balance. Their thermogenic activity is due to the presence of a mitochondrial uncoupling protein (UCP). Until recently, it was admitted that in rodents brown adipocytes were mainly located in classical brown adipose tissue (BAT). In the present study, we have investigated the presence of UCP protein or mRNA in white adipose tissue (WAT) of rats. Using polymerase chain reaction or Northern blot hybridization, UCP mRNA was detected in mesenteric, epidydimal, retroperitoneal, inguinal and particularly in periovarian adipose depots. The uncoupling protein was detected by Western blotting in mitochondria from periovarian adipose tissue. When rats were submitted to cold or to treatment with a beta-adrenoceptor agonist, UCP expression was increased in this tissue as in typical brown fat. Moreover, the expression was decreased in obese fa/fa rats compared to lean controls. Morphological studies showed that periovarian adipose tissue of rats kept at 24 degrees C contained cells with numerous typical BAT mitochondria with or without multilocular lipid droplets. Immunocytochemistry confirmed that multilocular cells expressed mitochondrial UCP. Furthermore, the number of brown adipocytes and the density of mitochondrial cristae increased in parallel with exposure to cold. These results demonstrate that adipocytes expressing UCP are present in adipose deposits considered as white fat. They suggest the existence of a continuum in rodents between BAT and WAT, and a great plasticity between adipose tissue phenotypes. The physiological importance of brown adipocytes in WAT and the regulation of UCP expression remain open questions.

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.

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