Overexpression of PGC-1ß improves insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes.

The co-transcription factor peroxisome proliferator-activated receptor γ coactivator-1ß (PGC-1ß) was first identified in 2002. Although the function of PGC-1ß in white adipose tissue (WAT) is largely unknown, it has been studied extensively in the liver, cardiac muscle, and skeletal muscle. Herein, we investigated PGC-1ß overexpression in 3T3-L1 adipocytes. The main findings were as follows: (i) 3T3-L1 adipocytes overexpressing PGC-1ß showed improved insulin sensitivity and elevated insulin-stimulated glucose uptake; (ii) mitochondrial cristae became broader and more ordered, additional smaller mitochondria emerged, mitochondrial DNA increased, and fission 1 protein (Fis1) mRNA expression was greatly elevated; (iii) intracellular ATP levels increased, but no changes were observed in mitochondrial membrane potential, uncoupling protein (UCP) mRNA expression, or reactive oxygen species (ROS) production; and (iv) mitochondrial metabolism factors, namely, acetyl-coenzyme A carboxylase 2 (ACC2) and hexokinase 2 (HK2) were downregulated, while cytochrome c oxidase subunit IV (COX IV) was upregulated. In conclusion, PGC-1ß affects not only insulin sensitivity but also mitochondrial biogenesis and function. We believe that the role of PGC-1ß is distinct from that of PGC-1α in WAT.