title: Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.
abstract: We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Je
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Okinawa Research Center Co. Ltd., 12-75 Suzaki, uruma-shi, Okinawa, Japan.
authors.forename: Je Tae
authors.initials: JT
authors.lastname: Woo
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan, Republic of Korea.
authors.forename: Mi Ji
authors.initials: MJ
authors.lastname: Jeong
authors.affiliation: School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan, Republic of Korea.
authors.forename: Un Ju
authors.initials: UJ
authors.lastname: Jung
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D050171:Dyslipidemias / Q000178:diet therapy / Q000209:etiology; D047309:Flavones / Q000008:administration & dosage* / Q000494:pharmacology; D006505:Hepatitis / Q000178:diet therapy* / Q000209:etiology; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000178:diet therapy* / Q000209:etiology; D009765:Obesity / Q000150:complications* / Q000209:etiology
chemical_list: D016207:Cytokines; D047309:Flavones; D008055:Lipids; C008661:nobiletin
keywords: Fatty acid oxidation; Inflammation; Insulin resistance; Nobiletin; Nonalcoholic fatty liver disease