Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Nobiletin and 3′-Demethyl Nobiletin Activate Brown Adipocytes upon β-Adrenergic Stimulation
Fumiko Kihara-Negishi Naoki OhkuraYuka TakahashiToshiyuki FujitaYasuhiro NakamuraKeiji MaruyamaTetsuta OshitariShinji Yamaguchi
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Supplementary material

2022 Volume 45 Issue 4 Pages 528-533

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Abstract

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.

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