Apolipoprotein A-I possesses an anti-obesity effect associated with increase of energy expenditure and up-regulation of UCP1 in brown fat.
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.
Ruan
Xiangbo
X
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.
Li
Zhenghu
Z
Zhang
Yixuan
Y
Yang
Ling
L
Pan
Yi
Y
Wang
Zhenzhen
Z
Feng
Gen-Sheng
GS
Chen
Yan
Y
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*
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