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标题：Nobiletin and 3′-Demethyl Nobiletin Activate Brown Adipocytes upon β-Adrenergic Stimulation
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作者：Fumiko Kihara-Negishi ; Naoki Ohkura ; Yuka Takahashi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2022
卷号：45
期号：4
页码：528-533
DOI：10.1248/bpb.b21-00988
语种：English
出版社：The Pharmaceutical Society of Japan
摘要：Brown adipose tissue (BAT) specifically regulates energy expenditure via heat production. Nobiletin (NOB), a natural polymethoxylated flavone present in citrus fruits, can activate thermogenesis in the BAT of high-fat diet-induced obese mice. The activity of BAT is directly regulated by β-adrenergic stimulation. In this study, we report the effects of NOB on BAT activation using β-adrenergic agonists. We observed that when HB2 brown adipocyte cell lines are stimulated with β-adrenergic agonists, NOB enhances the expression of uncoupling protein 1 (UCP1), which is associated with the mitochondrial energy metabolism in these cells. Moreover, NOB increases the mRNA expression of the brown adipokines neuregulin-4 (Nrg4) and fibroblast growth factor-21 (FGF-21) and the secretion of FGF-21. These results suggest that NOB can enhance the thermogenic functions of brown adipocytes and promote brown adipokine secretion due to enhanced β-adrenergic stimulation. In addition, 3′-demethyl nobiletin (3′-DMN), an NOB CYP-enzyme metabolite, can increase UCP1 mRNA expression. Both NOB and 3′-DMN significantly promoted mitochondrial membrane potential in HB2 adipocytes following β-adrenergic stimulation. Therefore, we believe that NOB could be a promising candidate for activating BAT under β-adrenergic stimulation and preventing the onset of obesity.
关键词：nobiletin metabolite;brown adipose tissue;thermogenesis;brown adipokine;sympathetic nerve system