Thermogenic adipocytes: From cells to physiology and medicine

Díaz, Mauricio Berriel; Herzig, Stephan; Vegiopoulos, Alexandros

doi:10.1016/j.metabol.2014.07.002

Cited by 37 publications

(49 citation statements)

References 107 publications

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“…In mice, BAT is located constitutively in the anterior subcutaneous region including the interscapular, axillary and cervical fat (Diaz et al, 2014). Brown adipocytes are characterized by multilocular lipid droplets and a high density of iron-containing mitochondria that give the eponymous appearance (Cinti, 2001).…”

Section: Introductionmentioning

confidence: 99%

Inter-organ regulation of adipose tissue browning

Wang

Yang

2016

Cell. Mol. Life Sci.

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Adaptive thermogenesis is an important component of energy expenditure. Brown adipocytes are best known for their ability to convert chemical energy into heat. Beige cells are brown-like adipocytes that arise in white adipose tissue in response to certain environmental cues to dissipate heat and improve metabolic homeostasis. A large body of intrinsic factors and external signals are critical for the function of beige adipocytes. In this review, we discuss recent advances in our understanding of neuronal, hormonal, and metabolic regulation of the development and activation of beige adipocytes, with a focus on the regulation of beige adipocytes by other organs, tissues, and cells. Understanding the cellular and molecular mechanisms of inter-organ regulation of adipose tissue browning may provide an avenue for combating obesity and associated diseases.

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Section: Introductionmentioning

confidence: 99%

Inter-organ regulation of adipose tissue browning

Wang

Yang

2016

Cell. Mol. Life Sci.

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“…This progression is mirrored by an increase in the energy expenditure required to maintain the core temperature. Green, energy expenditure due to basal metabolic rate; red, expenditure due to adaptive thermogenesis Aside from the anatomically defined intrascapular BAT, in mice non-shivering thermogenesis is generated in other adipose tissue depots, in particular inguinal, by "beige" or "brown-in-white (brite)" adipocytes (Ishibashi and Seale 2010;Petrovic et al 2010), whose mass and activity can be modulated by various signal hormones and cytokines, showing a remarkable plasticity (Diaz et al 2014). …”

Section: Figmentioning

confidence: 99%

“…Primary cultures of preadipocytes derived from the stromal vascular fraction of adipose tissues have been proven to be a robust experimental model to assess the effects of hormones and cytokines on their differentiation and function (Diaz et al 2014). Preadipocytes can be directed toward a white or beige phenotype by hormonal manipulation of the culture media, indirectly demonstrating the plasticity of adipose tissue depots.…”

Section: Manipulation Of the Human Adaptive Thermogenesis Response Bymentioning

confidence: 99%

Human Brown Adipose Tissue Plasticity: Hormonal and Environmental Manipulation

Celi

2017

Research and Perspectives in Endocrine Interactions

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Brown adipose tissue (BAT), brown-in-white ("brite") and "beige" adipocytes share the unique ability of converting chemical energy into heat and play a critical role in the adaptive thermogenesis response promoting nonshivering thermogenesis. Uncoupling Protein-1 (UCP1), which allows the uncoupling of substrate oxidation from phosphorylation of ADP, represents the molecular signature of BAT and beige adipocytes. Until recently, the physiologic role of BAT and beige adipocytes depots was thought to be limited to small mammalians and newborns.The discovery of BAT in adult humans and the demonstration of the presence of inducible BAT activity in white adipose tissue by beige adipocytes have generated enthusiasm as potential targets for treatment of obesity and other disorders due to sustained positive energy balance. These findings are particularly important since in vitro studies have demonstrated that preadipocytes can be directed toward a common brown phenotype by multiple pathways that, in turn, may be exploited for therapeutic interventions. In adult humans, BAT activity is more evident in deep neck fat depots and, to a lesser degree, in subcutaneous adipose tissue, with a transcriptome signature resembling the rodent beige fat. This observation supports the hypothesis that human BAT activity and capacity can be modulated. To this end, we have directed our translational research program toward the characterization of beige fat in humans and on the effects of hormonal and environmental drivers in the adaptive thermogenesis response. Mild cold exposure, within the temperature range commonly employed in climate-controlled buildings, is sufficient to generate a significant increase in non-shivering thermogenesis driven by BAT and beige adipocyte activation. In turn, adaptive thermogenesis generates a specific hormonal signature and promotes glucose disposal. Chronic exposure to mild cold induces expansion of BAT mass and activity, whereas exposure to warm climate abrogates them. Additionally, the metabolic effects of BAT mass expansion are evident only upon stimulation of BAT activity, indicating that both F. S. Celi (*) Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA e-mail: Francesco.celi@vchuhealth.org 2 expansion and activation of BAT are necessary and complementary strategies to pursue. From an experimental standpoint, human preadipocytes represent a viable experimental platform to mechanistically interrogate different pathways that are able to expand and activate browning. Our laboratory has focused on studying FGF-21, and FNDC5/irisin in their capacity to promote the browning process. Compared to a white differentiation medium, the addition of either FGF-21 or FNDC5 results in a reprogramming toward a brown phenotype, as indicated by the display of brown transcriptome signature and, functionally, by the increase in oxygen consumption following catecholamine treatment, indicating an increase in substrate utilizat...

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“…The success of this approach may therefore depend on generation of agents with better selectivity for the β3 adrenoreceptor, or alternative methods of activating BAT. A further development is the possibility that a subpopulation of white adipocytes have the potential to be ‘browned’, forming thermogenically active ‘beige’ adipose tissue and increasing the capacity for therapeutic energy wastage [86]. …”

Section: Likely Future Developmentsmentioning

confidence: 99%

The New Era of Drug Therapy for Obesity: The Evidence and the Expectations

Jones

Bloom

2015

Drugs

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There is an urgent need for effective pharmacological therapies to help tackle the growing obesity epidemic and the healthcare crisis it poses. The past 3 years have seen approval of a number of novel anti-obesity drugs. The majority of these influence hypothalamic appetite pathways via dopaminergic or serotoninergic signalling. Some are combination therapies, allowing lower doses to minimize the potential for off-target effects. An alternative approach is to mimic endogenous satiety signals using long-lasting forms of peripheral appetite-suppressing hormones. There is also considerable interest in targeting thermogenesis by brown adipose tissue to increase resting energy expenditure. Obesity pharmacotherapy has seen several false dawns, but improved understanding of the pathways regulating energy balance, and better-designed trials, give many greater confidence that recently approved agents will be both efficacious and safe. Nevertheless, a number of issues from preclinical and clinical development continue to attract debate, and additional large-scale trials are still required to address areas of uncertainty.

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Thermogenic adipocytes: From cells to physiology and medicine

Cited by 37 publications

References 107 publications

Inter-organ regulation of adipose tissue browning

Inter-organ regulation of adipose tissue browning

Human Brown Adipose Tissue Plasticity: Hormonal and Environmental Manipulation

The New Era of Drug Therapy for Obesity: The Evidence and the Expectations

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