Long-term effects of angiotensin-(1–7) on lipid metabolism in the adipose tissue and liver

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HIGHLIGHTSThe overexpression of Ang-(1–7) inhibits adipose tissue lipogenesis and LPL activity.Increased Ang-(1–7) plasma level regulates the adipose tissue LPL activity independently of the PPARγ expression.Increased Ang-(1–7) plasma level has a stimulatory effect on cytosolic lipase activity and inhibits FAS and FATP expression in the liver, suggesting a decrease in de novo fatty acid synthesis and fatty acid uptake.The data clearly show that Ang-(1–7) overexpression regulates lipid metabolism in the adipose tissue and liver.The angiotensin (Ang) converting enzyme 2/Ang-(1–7)/Mas axis has been described to have a beneficial role on metabolic disorders. In the present study, the use of a transgenic rat model that chronically overexpresses Ang-(1–7) enabled us to investigate the chronic effects of this peptide on lipid accumulation in the liver and adipose tissue. The transgenic group showed a marked tendency toward increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and decreased lipoprotein lipase (LPL) expression and activity in epididymal adipose tissue. We also showed that Mas receptor-knockout mice had decreased PPARγ expression in adipose tissue, accompanied by an increase in LPL activity. These results confirm the regulation of adipose tissue LPL activity by Ang-(1–7) and suggest that this occurs independent of PPARγ expression. The reduced adiposity index of transgenic rats, due to the effect of Ang-(1–7), was accompanied by a decrease in lipogenesis. These findings suggest a direct effect of Ang-(1–7) on lipogenesis, independent of the stimulatory effect of insulin. Furthermore, the decreased concentration of triacylglycerol in the liver of transgenic rats may result from increased activity of cytosolic lipases and decreased fatty acid uptake from the adipose tissue, determined from fatty acid-binding protein expression, and hepatic de novo fatty acid synthesis, evaluated by fatty acid synthase expression. The data clearly show that Ang-(1–7) regulates lipid metabolism in the adipose tissue and liver.

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