title: Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets.
abstract: OBJECTIVE
  Genistein has been suggested to prevent insulin resistance and its related diseases. We investigated the effects of dietary genistein at different levels on hepatic lipid levels and mitochondrial functions in mice fed high-fat diets.
  
  
  METHODS
  C57BL/6J mice were randomly divided into four groups and fed a high-fat diet containing genistein at levels of 0%, 0.1%, 0.2%, and 0.4% (HF, HF + 0.1G, HF + 0.2G, and HF + 0.4G) for 12 wk. We measured lipid levels in the blood and liver. We also observed messenger RNA (mRNA) expression of genes encoding proteins related to lipid and energy metabolism and antioxidant defense system and mitochondrial enzyme activities in the liver.
  
  
  RESULTS
  The induction of fatty liver by HF was substantially decreased in the HF + 0.2G and HF + 0.4G groups. Peroxisome proliferator-activated receptorgamma coactivator mRNA was increased by HF + 0.4G. Although genistein did not affect peroxisomal acyl-CoA oxidase mRNA expression, it increased medium-chain acyl-CoA dehydrogenase mRNA expression in a dose-dependent manner and HF + 0.2G increased uncoupling protein-2 mRNA expression two-fold relative to HF mice. Genistein decreased malondialdehyde levels and increased glutathione levels in liver homogenates, regardless of dose. The HF + 0.1G diet increased mitochondrial glutathione peroxidase activity and mitochondrial succinate dehydrogenase activity.
  
  
  CONCLUSIONS
  Although genistein at higher levels decreased hepatic fat accumulation possibly by increasing fatty acid oxidation and uncoupling protein, low-dose genistein increased mitochondrial enzyme activities in mice with fatty liver and obesity induced by high-fat diets.
authors.affiliation: Division of Metabolic Disease, Department of Biomedical Sciences, National Institute of Health, Seoul, Republic of Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Lee
authors.forename: Joo Sun
authors.initials: JS
authors.lastname: Choi
authors.forename: Mi Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
authors.forename: Yeon Sook
authors.initials: YS
authors.lastname: Lee
authors.forename: Jihyun
authors.initials: J
authors.lastname: Song
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism / Q000517:prevention & control*; D019833:Genistein / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D013385:Succinate Dehydrogenase / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D004041:Dietary Fats; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D008315:Malondialdehyde; D019833:Genistein; D010088:Oxidoreductases; D005979:Glutathione Peroxidase; C107176:peroxisomal acyl-CoA oxidase; D042962:Acyl-CoA Oxidase; D042964:Acyl-CoA Dehydrogenase; D013385:Succinate Dehydrogenase; D005978:Glutathione