Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity

Abstract

In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD+/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling. We also found that LBP increases acetyl-CoA carboxylase (ACC) phosphorylation and adipose triglyceride lipase (ATGL) protein expression and decreases fatty acid synthase (FAS) by activating the SIRT1/LKB1/AMPK pathway in vitro and in vivo. However, SIRT1 small interfering RNA (siRNA)-mediated knockdown reversed the LBP-mediated effects on ACC, FAS and ATGL. Moreover, LBP elevated carnitine palmitoyltransferase-1 alpha (CPT-1α) expression by suppressing malonyl-CoA accumulation. Taken together, our data indicate that LBP plays a vital role in the regulation of hepatic lipid metabolism and that pharmacological activation of SIRT1 by LBP may be a strategy for the prevention of NAFLD.

Lycium barbarum Polysaccharides Improve Testicular Spermatogenic Function in Streptozotocin-Induced Diabetic Rats

“…Our results showed that DM induced the downregulation of SIRT1 in the testes of diabetic rats and that LBP treatment increased the mRNA and protein expression levels of SIRT1 in the testes of diabetic rats. Our findings are in agreement with previous studies showing that LBP enhanced SIRT1 expression in hypoxic pulmonary vascular smooth muscle cells and in high-fat-dietinduced hepatic steatosis (35,36). The testis is a relatively hypoxic tissue, and HIF-1α regulates the primary transcriptional responses to hypoxic stress in normal and transformed cells, which plays an adaptive role in conferring protection against cell death in the testes (28).…”

An extract of Lycium barbarum mimics exercise to improve muscle endurance through increasing type IIa oxidative muscle fibers by activating ERRγ

“…Some recent studies have shown that LBP enhances mitochondrial function by activating AMPKα2 32,33 and regulates lipid metabolism by upregulating SIRT1 expression and increasing deacetylase activity. 34 These studies on the function of LBP in the regulation of metabolism in nonmuscle tissues also indirectly suggest that LBP may be the active compound. Next, we will try to separate and purify the L. barbarum polysaccharide, narrow the range of effective components according to molecular weight and other indicators, and purify the uniform polysaccharide, and finally find the functional uniform polysaccharide or the combination of several uniform polysaccharides.…”

Antitumor activity of Lycium barbarum polysaccharides with different molecular weights: an in vitro and in vivo study

“…Previous studies have shown that LBP could enhance the proliferation of splenocytes in mice [34,35], activate macrophages [36], and promote both the phenotypic and functional maturation of DC [37]. Besides, LBP also has various other biological activities, such as neuroprotective effects [38,39], radioprotective activity [40], cardioprotective activity [41], and hepatoprotective effects [42,43]. Clinical trials have shown that LBP had remarkable protective effects in patients with type 2 diabetes [44].…”