title: Apolipoprotein A-I possesses an anti-obesity effect associated with increase of energy expenditure and up-regulation of UCP1 in brown fat.
abstract: Apolipoprotein A-I (ApoA-I) is the most abundant protein constituent of high-density lipoprotein (HDL). Reduced plasma HDL and ApoA-I levels have been found to be associated with obesity and metabolic syndrome in human beings. However, whether or not ApoA-I has a direct effect on obesity is largely unknown. Here we analysed the anti-obesity effect of ApoA-I using two mouse models, a transgenic mouse with overexpression of ApoA-I and the mice administered with an ApoA-I mimetic peptide D-4F. The mice were induced to develop obesity by feeding with high fat diet. Both ApoA-I overexpression and D-4F treatment could significantly reduce white fat mass and slightly improve insulin sensitivity in the mice. Metabolic analyses revealed that ApoA-I overexpression and D-4F treatment enhanced energy expenditure in the mice. The mRNA level of uncoupling protein (UCP)1 in brown fat tissue was elevated by ApoA-I transgenic mice. ApoA-I and D-4F treatment was able to increase UCP1 mRNA and protein levels as well as to stimulate AMP-activated protein kinase (AMPK) phosphorylation in brown adipocytes in culture. Taken together, our results reveal that ApoA-I has an anti-obesity effect in the mouse and such effect is associated with increases in energy expenditure and UCP1 expression in the brown fat tissue.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Ruan
authors.forename: Zhenghu
authors.initials: Z
authors.lastname: Li
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D000071256:Uncoupling Protein 1; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D019440:Anti-Obesity Agents; D016632:Apolipoprotein A-I; C465468:D-4F peptide; D004041:Dietary Fats; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases