title: Apo-10'-lycopenoic acid, a lycopene metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice.
abstract: Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 9',10'-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. In the present study, male ob/ob mice were fed a liquid high-fat diet (60% energy from fat) with ALA supplementation (ALA group, 240 μg · kg body weight(-1) · d(-1)) or without ALA supplementation as the control (C group) for 16 wk. Steatosis, SIRT1 expression and activity, genes involved in lipid metabolism, and ALA concentrations in the livers of mice were examined. The results showed that ALA supplementation resulted in a significant accumulation of ALA in the liver and markedly decreased the steatosis in the ALA group without altering body and liver weights compared to the C group. The mRNA and protein levels of hepatic SIRT1 were higher in the ALA group compared to the C group. SIRT1 activity also was higher in the ALA group, as indicated by the lower levels of acetylated forkhead box class O1 protein levels. In addition, the mRNA level of acetyl CoA carboxylase 1 was significantly lower in the ALA group than in the C group. Because SIRT1 plays a key role in lipid homeostasis, the present study suggests that the lycopene metabolite, ALA, protects against the development of steatosis in ob/ob mice by upregulating SIRT1 gene expression and activity.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: Jayong
authors.initials: J
authors.lastname: Chung
authors.forename: Kyeongok
authors.initials: K
authors.lastname: Koo
authors.forename: Fuzhi
authors.initials: F
authors.lastname: Lian
authors.forename: Kang Quan
authors.initials: KQ
authors.lastname: Hu
authors.forename: Hansgeorg
authors.initials: H
authors.lastname: Ernst
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002338:Carotenoids / Q000008:administration & dosage* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage* / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D000077276:Lycopene; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; C523199:apo-10'-lycopenoic acid; D002338:Carotenoids; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000103:Acetyl-CoA Carboxylase; D000077276:Lycopene