Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis in Diabetic LDL Receptor–Deficient Mice

Abstract

Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMPactivated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor-deficient mice (DMLDLR ؊/؊ ). In HepG2 hepatocytes, polyphenols, including resveratrol (a major polyphenol in red wine), apigenin, and S17834 (a synthetic polyphenol), increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC), and they increased activity of AMPK with 200 times the potency of metformin. The polyphenols also prevented the lipid accumulation that occurred in HepG2 cells exposed to high glucose, and their ability to do so was mimicked and abrogated, respectively, by overexpression of constitutively active and dominant-negative AMPK mutants. Furthermore, treatment of DMLDLR ؊/؊ mice with S17834 prevented the decrease in AMPK and ACC phosphorylation and the lipid accumulation in the liver, and it also inhibited hyperlipidemia and the acceleration of aortic lesion development. These studies 1) reveal that inactivation of hepatic AMPK is a key event in the pathogenesis of hyperlipidemia in diabetes, 2) point to a novel mechanism of action of polyphenols to lower lipids by activating AMPK, and 3) emphasize a new therapeutic avenue to benefit hyperlipidemia and atherosclerosis specifically in diabetes via activating AMPK. Diabetes 55:2180 -2191, 2006

Effect of Sauropus Androgynus Leaves Extract (Sale) on Fat Deposition in Broiler Fed Low Protein Diets

“…Results of this study showed that the leaves extract of Sauropus androgynus at level of 9 g/kg diet could reduce the fat content of meat in broiler chickens fed a Effect Sauropus androgynus on Fat Disposition in Broiler (U. Santoso et al) 179 Compounds that play a role in lowering fat contents might be alkaloid and non alkaloid (Santoso et al, 2010b) (Yu et al, 2006), flavonoid (Zarrouki et al, 2010), tannin (Aiura and de Carvalho, 2007), polyphenol (Zang et al, 2006). SALE supplementation up to 9 g/kg diet could lower cholesterol contents of meat to normal contents (control).…”

“…This means SALE supplementation alone was not enough to lower cholesterol content to below control. Compounds that play a role in lowering cholesterol might be alkaloids and non-alkaloids (Santoso et al, 2010), saponins (Son et al, 2007), polyphenol (Ngamukote et al, 2011;Zang et al, 2006), flavonoid (Shrime et al, 2011). Patil et al (2010) reported that the reduction of cholesterol and triglycerides by alkaloids were in part caused by the reduction of lipogenic enzymes activities and increased bile acid excretion in feces.…”

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

“…Furthermore, the molecular mechanisms through which Scutellaria baicalensis acts are unknown. Recently, beneficial effects on obesity, diabetes and fatty liver have been reported for various flavonoids, which are thought to act through AMPK [9][10][11] . Therefore, the bioactive flavonoids such as baicalin in Scutellaria baicalensis are of particular interest.…”

“…Recently, polyphenols have been reported to reduce hyperlipidemia and hyperglycemia, and their effects on lipogenesis have been suggested to be mediated via activation of the AMP-activated protein kinase (AMPK) [9][10][11] . In this relation, AMPK has emerged as an important regulator of lipid metabolism at the cellular and systemic levels, and dysfunction of hepatic AMPK represents a key mechanism for hepatic lipid accumulation and hyperlipidemia with hepatic steatosis in genetically obese rodents [12,13] and in high-fat-fed mice [13] and rats [9,14] .…”

Effects of Equol on Oxidized Low-Density Lipoprotein-Induced Apoptosis in Endothelial Cells

“…These findings suggest that the prevention of LDL oxidation and suppression of OX-LDL-induced cellular effects can have a beneficial effect upon the progression of endothelial injury. The pathophysiological effects of OX-LDL on vascular cells have been well documented; recently, studies have reported that various components in foods can attenuate lipid oxidation [22][23][24][25] . Dietary isoflavones have been suggested to be protective against a range of diseases, including cardiovascular diseases, osteoporosis, and cancer, and have also been reported to alleviate menopausal symptoms in postmenopausal women [26][27][28] .…”