Antidiabetic and Antihyperlipidemic Effects of Clitocybe nuda on Glucose Transporter 4 and AMP‐Activated Protein Kinase Phosphorylation in High‐Fat‐Fed Mice

Abstract

The objective of this study was to evaluate the antihyperlipidemic and antihyperglycemic effects and mechanism of the extract of Clitocybe nuda (CNE), in high-fat- (HF-) fed mice. C57BL/6J was randomly divided into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed with a HF diet for 8 weeks. Then, the HF group was subdivided into five groups and was given orally CNE (including C1: 0.2, C2: 0.5, and C3: 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks. CNE effectively prevented HF-diet-induced increases in the levels of blood glucose, triglyceride, insulin (P < 0.001, P < 0.01, P < 0.05, resp.) and attenuated insulin resistance. By treatment with CNE, body weight gain, weights of white adipose tissue (WAT) and hepatic triacylglycerol content were reduced; moreover, adipocytes in the visceral depots showed a reduction in size. By treatment with CNE, the protein contents of glucose transporter 4 (GLUT4) were significantly increased in C3-treated group in the skeletal muscle. Furthermore, CNE reduces the hepatic expression of glucose-6-phosphatase (G6Pase) and glucose production. CNE significantly increases protein contents of phospho-AMP-activated protein kinase (AMPK) in the skeletal muscle and adipose and liver tissues. Therefore, it is possible that the activation of AMPK by CNE leads to diminished gluconeogenesis in the liver and enhanced glucose uptake in skeletal muscle. It is shown that CNE exhibits hypolipidemic effect in HF-fed mice by increasing ATGL expression, which is known to help triglyceride to hydrolyze. Moreover, antidiabetic properties of CNE occurred as a result of decreased hepatic glucose production via G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic states by CNE in HF-fed mice occurred by regulation of GLUT4, G6Pase, ATGL, and AMPK phosphorylation.

Potential Protective Activities of Extracts of Phellinus linteus and the Altered Expressions of GSTM3 on Age-Related Cataract

“…The experiment was determined using a procedure described elsewhere [ 20 , 21 ]. Total RNA was reverse transcribed to cDNA in a reaction mixture containing buffer, dNTP, the oligo (dT) primer, and Moloney murine leukemia virus reverse transcriptase and then heated at 90°C for 5 min to terminate the reaction.…”

“…The experiment was determined using a procedure described elsewhere [ 20 , 21 ]. Protein extractions and immunoblots for the determination of targeted proteins including GSTM3 were carried out on lenses from mice.…”

Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease

“…In mice with Streptozotocin (STZ)-induced liver damage (Box 3), L. nuda aqueous extract, as an adjuvant to an 8-week HFD diet, induced a reduction in IHTG content that was similar to the positive control group, treated with rosiglitazone, a PPAR-agonist antidiabetic drug. This extract induced an upregulation of PPAR-α mRNA levels and an increase in p-AMPK, paralleled by a decrease in the hepatic expression of gluconeogenic genes and an increase in GLUT-4 protein levels in liver and muscle tissue respectively [209]. Ganoderma lucidum ethanol extract also increased p-AMPK and p-ACC (inactive form) protein content in both cellular models (HepG2 and 3T3-L1) and HFD-fed mice after 16 weeks of feeding [210].…”

Cellular stress response mechanisms of Rhizoma coptidis: a systematic review

“…AMPK regulates the phosphorylation of PFK2 [ 37 ]. AMPK also can inhibit the activation of FAS, ACC, etc., to inhibit gluconeogenesis and glycogen formation [ 38 , 39 ]. AMPK participates in the regulation of lipid metabolism, which is related to SREBP1C [ 40 ].…”