Mangiferin Improved Palmitate-Induced-Insulin Resistance by Promoting Free Fatty Acid Metabolism in HepG2 and C2C12 Cells via PPARα: Mangiferin Improved Insulin Resistance

Abstract

Elevated free fatty acid (FFA) is a key risk factor for insulin resistance (IR). Our previous studies found that mangiferin could decrease serum FFA levels in obese rats induced by a high-fat diet. Our research was to determine the effects and mechanism of mangiferin on improving IR by regulating FFA metabolism in HepG2 and C2C12 cells. The model was used to quantify PA-induced lipid accumulation in the two cell lines treated with various concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased insulin-stimulated glucose uptake, via phosphorylation of protein kinase B (P-AKT), glucose transporter 2 (GLUT2), and glucose transporter 4 (GLUT4) protein expressions, and markedly decreased glucose content, respectively, in HepG2 and C2C12 cells induced by PA. Mangiferin significantly increased FFA uptake and decreased intracellular FFA and triglyceride (TG) accumulations. The activity of the peroxisome proliferator-activated receptor α (PPARα) protein and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) and the fatty acid β-oxidation rate corresponding to FFA metabolism were also markedly increased by mangiferin in HepG2 and C2C12 cells. Furthermore, the effects were reversed by siRNA-mediated knockdown of PPARα. Mangiferin ameliorated IR by increasing the consumption of glucose and promoting the FFA oxidation via the PPARα pathway in HepG2 and C2C12 cells.

Pharmacokinetic and metabolomic analyses of Mangiferin calcium salt in rat models of type 2 diabetes and non-alcoholic fatty liver disease

“…IR causes the body to produce compensation and secrete more insulin due to the body's decreased glucose regulation function. This result leads to the hydrolysis of triglycerides in the body and the increase of plasma fatty acid content, which ultimately promotes the increase of blood sugar and is excreted from the kidney [36,37]. At the same time, IR prevents insulin from efficiently inhibiting lipase activity.…”

Alismatis Rhizoma Triterpenes Alleviate High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle of Mice

“…Efficacy monitoring indicators were considered. Specifically, the level of FBG, FINS, HbA1c, FFA with a close relationship with IR occurrence and promotes the development of IR-type diabetes [ 39 ]) in serum was determined, and the HOMA-IR in each group was conducted. After ART treatment, FBG, FIINS, HbA1C, FFA concentration, and HOMA-IR were decreased compared with those of HFD group mice (Figures 3(b) – 3(f) ).…”

“…To further facilitate evidence-based cellular exploration, the IR model of C2C12 cells induced by PA was accustomed. After the ARTC intervention, we found that ARTC treatment promoted PA-induced glucose consumption in a dose-dependent manner [ 39 ]. The intervention of ART reduced the expression of TNF- α and MCP-1 levels in the IR model cells, implying the anti-inflammatory effect of ART.…”

Astragalosides IV Improves Palmitic Acid-induced Renal Tubular Epithelial Cells Injury Due to Inhibition of NLRP3 Inflammasome

“…Excessive FFAs-induced lipids deposition in tissues is one of the most important factors that induce oxidative stress and in ammation in various tissues and organs of the body [25][26][27]. PA is an important member of the saturated fatty acid family and closely involves in the occurrence and development of a lot of diseases in the body, such as insulin resistance and T2DM [28][29][30]. When the body's lipids are overloaded, the lipid balance is disrupted, leading to lipid metabolism system unable to proceed normally and cause lipotoxicity [31,32].…”