Diosgenin prevents high-fat diet-induced rat non-alcoholic fatty liver disease through the AMPK and LXR signaling pathways

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major public health concern worldwide. The aim of the present study was to observe the effect of diosgenin on NAFLD and investigate the underlying mechanisms. Diosgenin treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Diosgenin significantly inhibited high glucose (HG)-induced triglyceride (TG) accumulation and sterol regulatory element‑binding protein-1c (SREBP-1c) mRNA increase in HepG2 cells, which were partially abolished by the AMPK inhibitor compound C. Diosgenin also significantly inhibited the increase of liver X receptor (LXR) α mRNA induced by HG or T0901317. However, T0901317‑induced upregulation of LXRα and SREBP-1c mRNA was not blocked by compound C. Following a high-fat diet for 16 weeks, the body and liver weights of the experimental rats were significantly increased, but this effect was significantly suppressed by diosgenin. Diosgenin and fenofibrate ameliorated lipid deposition in the liver and reduced the increase of hepatic TG content. Diosgenin significantly decreased the alanine aminotransferase (ALT) level, whereas fenofibrate significantly increased the ALT and aspartate aminotransferase levels. Diosgenin also increased AMPK and ACC phosphorylation and suppressed LXRα in the liver. In conclusion, the results of the present study suggested that diosgenin is a potential agent for preventing the development of NAFLD through the AMPK and LXR signaling pathways.

Protective Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract against Hepatic Steatosis in High Fat Diet‐Induced Nonalcoholic Fatty Liver Disease Mice

“…Our results showed that ALM16 reversed the HFD-induced downregulation of CPT-1, involved in fatty acid oxidation, in the HFD-fed mice. Similarly, several studies have reported that the protective effects against hepatic steatosis are mediated by the downregulation of genes involved in lipogenesis and upregulation genes associated with fatty acid oxidation via enhanced AMPK signaling [60,61]. e results showed that AM treatment alone downregulated the FAS protein expression by activating AMPK phosphorylation, while it had no effect on the SREBP-1c and CPT-1 expressions.…”

Effect of celastrol on toll‑like receptor 4‑mediated inflammatory response in free fatty acid‑induced HepG2 cells

“…Although HepG2 cells originate from hepatoblastoma ( 16 ), the study by Gómez-Lechón et al ( 17 ) demonstrated that fat overaccumulation is induced in hepatic cells by FFA, and that human hepatocytes and HepG2 cells behave nearly the same. HepG2 cells are, therefore, generally accepted as a promising alternative to human hepatocytes for use as a cellular model of steatosis ( 17 – 19 ). HepG2 cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS; Gibco; Thermo Fisher Scientific, Inc.) and 1% penicillin/streptomycin at 37°C and 5% CO 2 .…”

Fenugreek (Trigonella Foenum-Graecum) Seed Flour and Diosgenin Preserve Endothelium-Dependent Arterial Relaxation in a Rat Model of Early-Stage Metabolic Syndrome

“…This finding corroborates the observation that diosgenin increases levels of antioxidant and hepatoprotective enzymes in the blood plasma and liver, with concomitant improvement of β-cell regeneration and insulin secretion in streptozotocin-induced diabetic rats [ 40 ]. It has been also found that diosgenin increases the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells, furthermore it suppresses LXRa in a rat model of non-alcoholic fatty liver disease (NAFLD), thus preventing development of NAFLD [ 48 ].…”