MMPP promotes adipogenesis and glucose uptake via binding to the PPAR gamma ligand binding domain in 3T3-L1 MBX cells

Abstract

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a transcription factor involved in adipogenesis, and its transcriptional activity depends on its ligands. Thiazolidinediones (TZDs), well-known PPAR gamma agonists, are drugs that improve insulin resistance in type 2 diabetes. However, TZDs are associated with severe adverse effects. As current therapies are not well designed, novel PPAR gamma agonists have been investigated in adipocytes. (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) is known to have anti-arthritic, anti-inflammatory, and anti-cancer effects. In this study, we demonstrated the adipogenic effects of MMPP on the regulation of PPAR gamma transcriptional activity during adipocyte differentiation in vitro. MMPP treatment increased PPAR gamma transcriptional activity, and molecular docking studies revealed that MMPP binds directly to the PPAR gamma ligand binding domain. MMPP and rosiglitazone showed similar binding affinities to the PPAR gamma. MMPP significantly promoted lipid accumulation in adipocyte cells and increased the expression of C/EBP beta and the levels of p-AKT, p-GSK3, and p-AMPK alpha at an early stage. MMPP enhanced the expression of adipogenic markers such as PPAR gamma, C/EBP alpha, FAS, ACC, GLUT4, FABP4 and adiponectin in the late stage. MMPP also improved insulin sensitivity by increasing glucose uptake. Thus, MMPP, as a PPAR gamma agonist, may be a potential drug for type 2 diabetes and metabolic disorders, which may help increase adipogenesis and insulin sensitivity.