Research Topic

Current Challenges for Targeting Brown Fat Thermogenesis to Combat Obesity

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Ten years have passed since metabolically active brown adipose tissue (BAT) was identified in healthy adult humans. Over the past decade, researchers have provided evidence of certain expression of thermogenic molecule uncoupling protein 1 (UCP1) in human BAT and its energy dissipating capacity in various ...

Ten years have passed since metabolically active brown adipose tissue (BAT) was identified in healthy adult humans. Over the past decade, researchers have provided evidence of certain expression of thermogenic molecule uncoupling protein 1 (UCP1) in human BAT and its energy dissipating capacity in various models, both in vitro and in vivo. Furthermore, clinical cross-sectional analysis suggests that decline in BAT activity with aging incites the development of obesity and insulin resistance. These major observations provided the impetus to research BAT as a potential target for the treatment of obesity. To this end, several intervention studies demonstrated evidence that cold exposure and adrenomimetic pharmacological agents strongly activate BAT thermogenesis in healthy adults. However, the extent to which stimulating BAT thermogenesis decreases adiposity in humans remains unclear. Moreover, such BAT-targeting regimens that require general sympathetic nervous stimulation may not be applicable for obese and diabetic patients, because of potential negative side-effects on cardiovascular function.
The identification of novel molecular circuits responsible for BAT thermogenesis may lead to the discovery of targetable pathways for the development of practicable therapies for obesity and related metabolic disorders. Recent studies in mice have made new advances in this regard. While thermogenic activity of brown adipocytes largely relies on UCP1 function, brown-like (brite/beige) adipocytes were shown to utilize alternative thermogenic pathways that are independent of UCP1. Additionally, although the sympathetic nervous system is undoubtedly a central regulator of BAT-mediated thermogenesis, peripheral organ-derived endocrine factors or endogenous production of metabolites of fatty acids are also capable of triggering thermogenesis in BAT. Activating these non-canonical thermogenic mechanisms through either genetic manipulation or pharmacological agents sufficiently suppresses consequences of obesity in mice. These results raise an obvious question: whether novel molecular circuits may also play regulatory roles in thermogenic activity of human BAT and, more importantly, whether these can be therapeutic targets to treat metabolic diseases in obese individuals.
To bridge basic research with clinical trials, this Research Topic aims to highlight current evidence of endogenous and environmental regulators of human BAT function together with new advances in our understanding of thermogenic adipocyte biology, as observed in animals in the form of Original Research, Review, and Mini-Review articles.

We will examine the following areas:

- Clinical research topics (1): Current understanding of human BAT physiology and therapeutic potentials
- Clinical research topics (2): Methodological advances in functional assessment of human BAT
- Basic research topics (1): Molecular and neural mechanisms that regulate BAT function and homeostasis
- Basic research topics (2): Physiological regulators of adipose thermogenesis
- Basic research topics (3): Identification and characterization of thermogenic precursor cells

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.


Keywords: Brown fat, Beige fat, Activation, Obesity, Diabetes


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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