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Article Title

Food factors that mimic bile acid functions

Authors

R. Sato

Abstract

TGR5 is a member of the G protein-coupled receptor family and is activated by bile acids. TGR5 is thought to be a promising food factor target for preventing metabolic diseases because the activation of TGR5 prevents obesity and hyperglycemia in mice fed a high-fat diet. In the present study, we established an evaluation system for the TGR5 ligand activity, and identified a limonoid nomilin as an activator of TGR5 from among approximate 150 purified food compounds. Unlike bile acids, nomilin did not exhibit the farnesoid X receptor ligand activity. Although the nomilin derivative obacunone was capable of activating TGR5, limonin (the most abundant limonoid in citrus seeds) was not a TGR5 activator. When male C57BL/6J mice fed a high-fat diet for 9 weeks were further fed a high-fat diet either alone or supplemented with 0.2% w/w nomilin for 77 days, nomilin-treated mice had lower body weight, serum glucose, serum insulin, and enhanced glucose tolerance. Our results suggest a novel biological function of nomilin as an agent having anti-obesity and anti-hyperglycemic effects that are likely to be mediated through the activation of TGR5.

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