Abstract
We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.
Highlights
We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity
Previous pharmacokinetic studies reported that the Cmax of C3G is 0.14–14 μM11,36–38, suggesting that dietary C3G activates the PPARα and PPARγ subtypes in vivo. These results demonstrate that PPARα may be a major and direct target protein of C3G during its regulation of hyperlipidaemia and insulin resistance and it is possible that C3G activates PPARγ, which further contributes to the improvement of lipid and glucose metabolism
The oral administration of C3G to high-fat diet (HFD)-fed mice for 8 weeks reduced hepatic and plasma TG concentrations and induced hepatic fatty acid oxidation, increased brown adipocyte activity, oxygen consumption, and energy expenditure, but these effects of C3G were reversed in PPARα-deficient mice
Summary
We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. PPARα is widely expressed in different tissues with high expression levels in liver and skeletal muscle that regulates the expression of genes encoding enzymes and transport proteins that control lipid homeostasis and stimulates fatty acid oxidation and improves lipoprotein metabolism[22,23]. PPARγ agonists, thiazolidinediones, are used as prescribed drugs for the treatment of type 2 diabetes
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