Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice

Abstract

Isoliquiritigenin (ILG) is a flavonoid constituent of Glycyrrhizae plants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (w/w) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancing β-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.

A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice

“…The octapeptide GPETAFLR prevents the weight gain resulting from a diet rich in fat in contrast to other substances such as isoliquiritigenin with hepatoprotective properties that do not have the capacity to prevent weight gain. 32 It can be said that GPETAFLR interferes by preventing the progression of the main cause of NAFLD: obesity.…”

“…These values were also obtained in other similar studies on HFD-induced obese animals. 19,32,[35][36][37] All these parameters of the pathology were palliated with the treatment with GPETAFLR owing to the fact that liver weight and liver fat accumulation were lower in the animals treated with the octapeptide. The factors that can influence the minor accumulation of hepatic fat in these individuals are a decreased gene expression of FAS and an increased expression of the enzymes that increase energy metabolism, such as UCP1 and PPARα.…”

“…Other plant bioactive substances have been shown to have effects by decreasing the resistance to leptin without significantly affecting the body weight. 32…”

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…Finally, Isoliquiritigenin at a low dose ameliorated insulin resistance and NAFLD in diet-induced obese mice. Isoliquiritigenin administration to HFD-fed mice decreased body fat mass and plasma cholesterol as well as alleviated hepatic steatosis (smaller lipid droplets) with no changes in TG and FFA serum levels [ 400 ]. It has been described that isoliquiritigenin suppressed the expression of lipogenic genes ( Fasn and Scd1 ) and increased FAO activity.…”

Interactions between leptin and insulin resistance in patients with prediabetes, with and without NAFLD

“…In patients with NAFLD, high concentrations of leptin have been observed together with diminished levels of adiponectin (19). Also, the degree of severity of NAFLD correlated with the levels of serum leptin (20). These consequences (dyslipidaemia, insulin resistance, chronic low-grade inflammation and NAFLD) have been investigated for favorable effects of a variety of natural phytochemicals or other antidiabetic drugs (4,21).…”