Abstract
Beige adipocytes emerge postnatally within the white adipose tissue in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for antiobesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. We report that a combination of mild cold exposure at 17°C and capsinoids, a nonpungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorates diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the β2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. We document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole-body energy expenditure by combining dietary components and environmental cues.
© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
MeSH terms
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Acclimatization*
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Adipocytes, Beige / cytology
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Adipocytes, Beige / drug effects
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Adipocytes, Beige / pathology
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Adipocytes, Beige / physiology*
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Adipogenesis* / drug effects
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Adrenergic beta-2 Receptor Agonists / pharmacology
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Adrenergic beta-2 Receptor Agonists / therapeutic use
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Adrenergic beta-2 Receptor Antagonists / pharmacology
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Adrenergic beta-2 Receptor Antagonists / toxicity
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Animals
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Anti-Obesity Agents / agonists
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Anti-Obesity Agents / antagonists & inhibitors
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Anti-Obesity Agents / therapeutic use*
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Capsaicin / agonists
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Capsaicin / analogs & derivatives*
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Capsaicin / antagonists & inhibitors
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Capsaicin / chemistry
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Capsaicin / therapeutic use
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Cells, Cultured
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Cold Temperature
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Dietary Supplements*
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Energy Metabolism / drug effects
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Gene Expression Regulation / drug effects
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Hydrogenation
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Male
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Mice, Inbred C57BL
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Mice, Transgenic
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Obesity / chemically induced
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Obesity / metabolism
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Obesity / pathology
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Obesity / prevention & control*
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Oxygen Consumption / drug effects
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Protein Stability / drug effects
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Random Allocation
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Receptors, Adrenergic, beta-2 / chemistry
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Receptors, Adrenergic, beta-2 / genetics
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Receptors, Adrenergic, beta-2 / metabolism
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Signal Transduction / drug effects
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Adrenergic beta-2 Receptor Agonists
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Adrenergic beta-2 Receptor Antagonists
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Anti-Obesity Agents
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DNA-Binding Proteins
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Prdm16 protein, mouse
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Receptors, Adrenergic, beta-2
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Transcription Factors
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nordihydrocapsiate
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capsiate
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Capsaicin