Diosgenin Ameliorated Type II Diabetes-Associated Nonalcoholic Fatty Liver Disease through Inhibiting De Novo Lipogenesis and Improving Fatty Acid Oxidation and Mitochondrial Function in Rats

Abstract

Diosgenin (DIO) is a dietary and phytochemical steroidal saponin representing multiple activities. The present study investigated the protective effect of DIO on type II diabetes-associated nonalcoholic fatty liver disease (D-NAFLD). The rat model was established by high-fat diet and streptozotocin injection and then administered DIO for 8 weeks. The results showed that DIO reduced insulin resistance index, improved dyslipidemia, and relieved pancreatic damage. DIO decreased hepatic injury markers, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). H&E staining showed that DIO relieved hepatic lipid deposition. Mechanistically, DIO inhibited hepatic de novo lipogenesis (DNL) and increased fatty acid β-oxidation (FAO) through regulation of the AMPK-ACC/SREBP1 pathway. Endoplasmic reticulum (ER) stress was inhibited by DIO through regulation of PERK and IRE1 arms, which may then inhibit DNL. DIO also decreased reactive oxygen species (ROS) and enhanced the antioxidant capacity via an increase in Superoxide dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GPx) activities. The mitochondria are the site for FAO, and ROS can damage mitochondrial function. DIO relieved mitochondrial fission and fusion disorder by inhibiting DRP1 and increasing MFN1/MFN2 expressions. Mitochondrial apoptosis was then inhibited by DIO. In conclusion, the present study suggests that DIO protects against D-NAFLD by inhibiting DNL and improving FAO and mitochondrial function.

Therapeutic Potential of Diosgenin in Amelioration of Carbon Tetrachloride-Induced Murine Liver Injury

“…Prolonged oral administration of diosgenin dose-dependently restored the CCL4-induced changes and accordingly improved liver function. This positive effect of diosgenin has also been reported in other studies related to liver injury [13][14][15][16]. In a mouse model of acute liver failure induced by LPS-D-galactosamine, diosgenin This document was downloaded for personal use only.…”

“…Diosgenin could decrease liver injury markers, such as AST and ALT. It also inhibited hepatic lipogenesis and elevated fatty acid β-oxidation [15].…”

“…In an animal model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), diosgenin administration prevented the development of NAFLD [14]. In type II diabetes-associated NAFLD, diosgenin decreased serum liver enzyme levels; in the same group, antioxidant capacity was increased as well [15]. Another study indicated that diosgenin alleviated nonalcoholic steatohepatitis and also reduced the serum levels of liver enzymes [16].…”

Berberine Ameliorates Metabolic-Associated Fatty Liver Disease Mediated Metabolism Disorder and Redox Homeostasis by Upregulating Clock Genes: Clock and Bmal1 Expressions

“…Insulin resistance (IR) is closely associated with many metabolic disorders, including hypertension, hyperlipidemia, atherosclerosis, and a fatty liver [ 4 ]. Increasing evidence suggests that IR plays critical roles in the progression of MAFLD through mediating glucose metabolism disorder and redox homeostasis [ 5 , 6 ]. However, the current molecular knowledge of IR on MAFLD remains poorly understood.…”

Icariin Alleviates Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome by Improving Liver Fatty Acid Oxidation and Inhibiting Lipid Accumulation

“…Four main pathways regulate them: uptake of circulating lipids, de novo lipogenesis (DNL), fatty acid oxidation (FAO), and export of lipids from very low-density lipoproteins (VLDL). Numerous studies in rodents have attempted to indirectly promote FAO to reduce systemic obesity and prevent the development of metabolic disorders associated with obesity [ 12 , 13 ]. The liver is largely dependent on fatty acid transporters for the uptake of circulating fatty acids, with a smaller contribution from passive diffusion [ 14 ].…”