title: Preventive effect of geniposide on metabolic disease status in spontaneously obese type 2 diabetic mice and free fatty acid-treated HepG2 cells.
abstract: Accumulation of visceral fat induces various symptoms of metabolic syndrome such as insulin resistance and abnormal glucose/lipid metabolism and eventually leads to the onset of ischemic cerebrovascular diseases. Geniposide, which is iridoid glycoside from the fruit of Gardenia jasminoides ELLIS, is recognized as being useful against hyperlipidemia and fatty liver. In order to clarify the effect of geniposide on metabolic disease-based visceral fat accumulation and the relevant molecular mechanism, experiments were performed in spontaneously obese Type 2 diabetic TSOD mice and the free fatty acid-treated HepG2 cells. In the TSOD mice, geniposide showed suppression of body weight and visceral fat accumulation, alleviation of abnormal lipid metabolism and suppression of intrahepatic lipid accumulation. In addition, geniposide alleviated abnormal glucose tolerance and hyperinsulinemia, suggesting that geniposide has an insulin resistance-alleviating effect. Next, in order to investigate the direct effect of geniposide on the liver, the effect on the free fatty acid-treated HepG2 fatty liver model was investigated using genipin, which is the aglycone portion of geniposide. Genipin suppressed the intracellular lipid accumulation caused by the free fatty acid treatment and also significantly increased the intracellular expression of a fatty acid oxidation-related gene (peroxisomal proliferator-activated receptor: PPARα). From these results, it was confirmed that geniposide has an anti-obesity effect, an insulin resistance-alleviating effect and an abnormal lipid metabolism-alleviating effect, and the metabolite genipin shows a direct effect on the liver, inducing expression of a lipid metabolism-related gene as one of its molecular mechanisms.
authors.affiliation: Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Ishikawa 920–1192, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kojima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nagareda
authors.forename: Michiru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Junko
authors.initials: J
authors.lastname: Ishizaki
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Aburada
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism; D032062:Gardenia; D018149:Glucose Intolerance / Q000150:complications / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D039823:Iridoids / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000150:complications / Q000378:metabolism / Q000517:prevention & control; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000378:metabolism; D008517:Phytotherapy; D028321:Plant Preparations / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019440:Anti-Obesity Agents; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D039823:Iridoids; D028321:Plant Preparations; C007835:geniposide