Protective Effects of Licochalcone A Ameliorates Obesity and Non-Alcoholic Fatty Liver Disease Via Promotion of the Sirt-1/AMPK Pathway in Mice Fed a High-Fat Diet

Abstract

Licochalcone A is a chalcone isolated from Glycyrrhiza uralensis. It showed anti-tumor and anti-inflammatory properties in mice with acute lung injuries and regulated lipid metabolism through the activation of AMP-activated protein kinase (AMPK) in hepatocytes. However, the effects of licochalcone A on reducing weight gain and improving nonalcoholic fatty liver disease (NAFLD) are unclear. Thus, the present study investigated whether licochalcone A ameliorated weight loss and lipid metabolism in the liver of high-fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed an HFD to induce obesity and NAFLD, and then were injected intraperitoneally with licochalcone A. In another experiment, a fatty liver cell model was established by incubating HepG2 hepatocytes with oleic acid and treating the cells with licochalcone A to evaluate lipid metabolism. Our results demonstrated that HFD-induced obese mice treated with licochalcone A had decreased body weight as well as inguinal and epididymal adipose tissue weights compared with HFD-treated mice. Licochalcone A also ameliorated hepatocyte steatosis and decreased liver tissue weight and lipid droplet accumulation in liver tissue. We also found that licochalcone A significantly regulated serum triglycerides, low-density lipoprotein, and free fatty acids, and decreased the fasting blood glucose value. Furthermore, in vivo and in vitro, licochalcone A significantly decreased expression of the transcription factor of lipogenesis and fatty acid synthase. Licochalcone A activated the sirt-1/AMPK pathway to reduce fatty acid chain synthesis and increased lipolysis and β-oxidation in hepatocytes. Licochalcone A can potentially ameliorate obesity and NAFLD in mice via activation of the sirt1/AMPK pathway.

Probiotic Mixture of Lactobacillus plantarum Strains Improves Lipid Metabolism and Gut Microbiota Structure in High Fat Diet-Fed Mice

“…A significant elevated TG concentration in the liver was observed in the HFD group, which was consistent with the large number of lipid droplets in liver histopathological sections of the HFD group observed in our previous studies , implying that hepatic steatosis occurred. These results were in agreement with the earlier reports in which, obese mice suffered from non-alcoholic hepatic steatosis (Liou et al, 2019). However, it is noteworthy that mixed lactobacilli treatment substantially attenuated hepatic steatosis.…”

“…AMPK is a known cellular energy sensor that shuts down anabolic pathways such as fatty acid synthesis (Hardie and Pan, 2002). ACC and FAS are key enzymes in fatty acid synthesis (Liou et al, 2019). Specifically, activation of AMPK-α stimulates ACC phosphorylation, which blocks the expression of FAS (Liou et al, 2019).…”

“…ACC and FAS are key enzymes in fatty acid synthesis (Liou et al, 2019). Specifically, activation of AMPK-α stimulates ACC phosphorylation, which blocks the expression of FAS (Liou et al, 2019). HSL is the rate-limiting enzyme in the breakdown of triglycerides in adipose tissue (Liou et al, 2019).…”

“…Specifically, activation of AMPK-α stimulates ACC phosphorylation, which blocks the expression of FAS (Liou et al, 2019). HSL is the rate-limiting enzyme in the breakdown of triglycerides in adipose tissue (Liou et al, 2019). In the present study, the mRNA levels of AMPK-α and HSL were remarkably reduced in the HFD group compared with the control group, while the mRNA levels of ACC and FAS were significantly elevated, and these changes were completely eliminated by the treatment of mixed lactobacilli, similar to the study by Qiao et al (Qiao et al, 2015).…”

Characterizing the Retinal Phenotype in the High-Fat Diet and Western Diet Mouse Models of Prediabetes

“…The high-fat diet (HFD) mouse model has been described as a robust model for investigating obesity-associated T2D and its related metabolic complications [7]. Studies have shown that HFD-fed mice develop obesity, impaired glucose tolerance, and reduced insulin sensitivity [8,9] with systemic manifestations involving adipose tissue [10], liver [8], and kidneys [11]. However, the ocular changes associated with the HFD model have not been fully investigated.…”