title: A Synergistic Antiobesity Effect by a Combination of Capsinoids and Cold Temperature Through Promoting Beige Adipocyte Biogenesis.
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.
authors.affiliation: Frontier Fusion Research, Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA.
authors.forename: Kana
authors.initials: K
authors.lastname: Ohyama
authors.affiliation: Frontier Fusion Research, Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nogusa
authors.affiliation: Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: Frontier Fusion Research, Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Frontier Fusion Research, Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan makoto_bannai@ajinomoto.com.
authors.forename: Makoto
authors.initials: M
authors.lastname: Bannai
authors.affiliation: Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA skajimura@diabetes.ucsf.edu.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kajimura
mesh_terms: D000064:Acclimatization; D000069797:Adipocytes, Beige / Q000166:cytology / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D050156:Adipogenesis / Q000187:drug effects; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D019440:Anti-Obesity Agents / Q000819:agonists / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D002211:Capsaicin / Q000819:agonists / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000627:therapeutic use; D002478:Cells, Cultured; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004734:Energy Metabolism / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006865:Hydrogenation; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010101:Oxygen Consumption / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D011897:Random Allocation; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D019440:Anti-Obesity Agents; D004268:DNA-Binding Proteins; C521133:Prdm16 protein, mouse; D018343:Receptors, Adrenergic, beta-2; D014157:Transcription Factors; C000619851:nordihydrocapsiate; C470213:capsiate; D002211:Capsaicin