Abstract
Nonalcoholic fatty liver disease (NAFLD) is recognized as the liver component of metabolic syndrome. The regulation of hepatic lipid should be emphasized to prevent accompanying illness. As AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP) regulate lipid metabolism, CD36 and fatty acid synthase (FAS) promote lipid uptake and lipogenesis respectively, while acetyl-CoA carboxylase (ACC) is an indicator of negative feedback. The increase of IRS-1 phosphorylation at the residue ser307 (p-ser307-IRS-1) and decrease of p-ser473-Akt (p-Akt) are viewed as the insulin resistance markers, and our previous reports suggested dipeptidyl peptidase-4 (DPP-4) mediates insulin resistance, the crucial factor of metabolic syndrome. Abelmoschus esculentus (AE) fruit is well-known for its antidiabetic utility. We had isolated several AE subfractions by successive steps, and found that F1 and F2 were especially valid in suppressing DPP-4 signaling. Since little is known if AE works on NAFLD, now we first attempt to investigate whether AE is useful to attenuate hepatic lipogenesis and lipid uptake in liver cells, along with improving the metabolic targets. We demonstrated that AE subfractions attenuated the hepatic lipid accumulation induced by free fatty acids. Treatment of AE alleviated FAS and returned the level of p-ser79-ACC (p-ACC). Although F1 was more effective on AMPK, F2 seemed more stable to attenuate SREBP-1. Moreover, as fatty acids stimulated the expression of CD36, F2 showed a superior effect to down-regulate the lipid uptake. Both AE subfractions reduced the generation of ROS, decreased the level of p-ser307-IRS-1, and restored the expression of p-Akt. Moreover, treatment of DPP-4 inhibitor linagliptin revealed that, AE could prevent the hepatic lipogenesis, oxidative burden, and the related insulin resistance via downregulating DPP-4. In conclusion, the present investigation revealed that AE, especially F2, is potential to be developed as adjuvant to prevent NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD), which covers a wide spectrum of manifestations including liver steatosis, is recognized as the liver component of metabolic syndrome [1]
We demonstrated that Abelmoschus esculentus (AE) subfractions attenuated the hepatic lipid accumulation induced by free fatty acids
acetyl-CoA carboxylase (ACC) is the enzyme catalyzing the carboxylation of acetyl-CoA to produce malonyl-CoA, which is the important substrate of the initiation step of fatty acid synthesis [4], Apart from endogenous fatty acid synthesis, the uptake of fatty acid would be bound to lipid metabolism
Summary
Nonalcoholic fatty liver disease (NAFLD), which covers a wide spectrum of manifestations including liver steatosis, is recognized as the liver component of metabolic syndrome [1]. Liver plays an essential role to regulate plasma lipid level, while the overload of hepatic lipid uptake burdens liver function and relates to the subsequent development of inflammation and fibrosis [2]. It was reported lipotoxicity and oxidative stress are the important mediators in NAFLD pathogenesis [3]. ACC is the enzyme catalyzing the carboxylation of acetyl-CoA to produce malonyl-CoA, which is the important substrate of the initiation step of fatty acid synthesis [4], Apart from endogenous fatty acid synthesis, the uptake of fatty acid would be bound to lipid metabolism. CD36 is a wide-expressed transmembrane glycoprotein serves many functions, including the uptake of the long-chain fatty acid across cell membranes. The rate of uptake is primarily governed by the presence of CD36 at cell surface, regulated by the subcellular vesicular recycling from endosomes to the plasma membrane [5]
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