MDG-1, a Potential Regulator of PPARα and PPARγ, Ameliorates Dyslipidemia in Mice

Abstract

Hyperlipidemia is a serious epidemic disease caused by lipid metabolism disorder, which is harmful to human health. MDG-1, a β-d-fructan polysaccharide extracted from Ophiopogon japonicus, has been shown to improve abnormal blood lipid levels and alleviate diabetes. However, the underlying mechanism on hyperlipidemia is largely unknown. In this study, male C57BL/6 mice were randomly separated into three groups, respectively: low-fat diet (Con), high-fat diet (HFD), and high-fat diet plus 5‰ MDG-1 (HFD + MDG-1). Body weight was measured and the serum lipid levels were analyzed. Using gene microarray, various core pathways, together with levels of gene expression within hepatocytes, were analyzed. RT-PCR was used to confirm the identity of the differentially expressed genes. MDG-1 could prevent obesity in HFD-induced mice and improve abnormal serum lipids. Besides, MDG-1 could regulate hyperlipidemia symptoms, specifically, and decrease fasting blood glucose, improve glucose tolerance, and ameliorate insulin resistance. According to results from gene microarray, most of the identified pathways were involved in the digestion and absorption of fat, biosynthesis, and catabolism of fatty acids as well as the secretion and biological synthesis of bile acids. Furthermore, MDG-1 may act upon peroxisome proliferator-activated receptors (PPAR) α and γ, activating PPARα whilst inhibiting PPARγ, thus having a potent hypolipidemic effect.

Metabolomics insights into the modulatory effects of long-term compound polysaccharide intake in high-fat diet-induced obese rats

“…For example, Chang et al [ 7 ] discovered that Ganoderma lucidum reduced body weight, fat accumulation, inflammation, endotoxemia and insulin resistance in obese mice and prevented obesity-related metabolic disorders in obese individuals. Additionally, it was also reported that MDG-1, a β-D-fructan polysaccharide extracted from Ophiopogon japonicus , could prevent the development of obesity and ameliorate dyslipidemia in high-fat diet (HFD)-induced obese mice [ 9 , 10 ]. Interestingly, a compound polysaccharide, which is a mixture of lentinan and Flos Lonicera polysaccharides (LF), improved obesity and its related complications in our research studies (unpublished data).…”

Trigonelline reduced diabetic nephropathy and insulin resistance in type�2 diabetic rats through peroxisome proliferator‑activated receptor‑γ

“…Particularly, PPAR-γ serves a vital role in adipocyte differentiation, glucolipid metabolism and insulin resistance (24). PPAR-γ is a class of ligand-activated nuclear transcription factor that can regulate the expression of multiple key genes during glucose and lipid metabolism (25). Notably, leptin is involved in regulating glucose and lipid metabolism in the liver (25).…”

“…PPAR-γ is a class of ligand-activated nuclear transcription factor that can regulate the expression of multiple key genes during glucose and lipid metabolism (25). Notably, leptin is involved in regulating glucose and lipid metabolism in the liver (25). Consequently, leptin may enhance the synthesis of triglycerides and reduce the production of hepatic glycogen (26).…”

Genistein inhibits AOM/DSS-induced colon cancer by regulating lipid droplet accumulation and the SIRT1/FOXO3a pathway in high-fat diet-fed female mice

“…Upregulation of LD-associated proteins such as members of the PLIN family, CIDEC, CIDEA, HILPDA, FITM1, FITM2, and G0S2 by PPAR-γ has been considered as a mechanistic link between lipid uptake and regulation of lipid storage capacity (Montserrat & Kersten, 2017). Mice with dyslipidemia have high PPAR-γ level, whereas PPAR-γ inhibition can prevent HFD-induced hyperlipidemia and obesity Wang, Shi, Joyce, Wang, & Feng, 2017). SIRT1, a protein deacetylase, represses PPAR-γ and inhibits fatty acid biosynthesis (Picard et al, 2004).…”