d-4f-peptide and Obesity

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.

Topics: Adipocytes; Adipose Tissue, Brown; Adiposity; AMP-Activated Protein Kinase Kinases; Animals; Anti-Obesity Agents; Apolipoprotein A-I; Cells, Cultured; Dietary Fats; Energy Metabolism; Feeding Behavior; Humans; Insulin; Ion Channels; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondrial Proteins; Obesity; Phosphorylation; Protein Kinases; Uncoupling Protein 1; Up-Regulation