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Long‐term dietary supplementation with low‐dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet‐induced obesity
Author(s) -
Kim YoungJe,
Choi MyungSook,
Woo Je Tae,
Jeong Mi Ji,
Kim Sang Ryong,
Jung Un Ju
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201600889
Subject(s) - endocrinology , medicine , insulin resistance , proinflammatory cytokine , adipose tissue , steatosis , fatty liver , triglyceride , nonalcoholic fatty liver disease , lipogenesis , chemistry , inflammation , insulin , cholesterol , biology , disease
Scope We evaluated the long‐term effect of low‐dose nobiletin (NOB), a polymethoxylated flavone, on diet‐induced obesity and related metabolic disturbances. Methods and results C57BL/6J mice were fed a high‐fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation‐related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro‐inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB‐supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non‐HDL‐cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation‐related enzymes. Hepatic proinflammatory TNF‐α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB‐supplemented mice. Conclusion These findings suggest that long‐term supplementation with low‐dose NOB can protect against HFD‐induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity.