Co-overexpression of the caloric restriction-induced mitochondrial factors PGC-1α and MIPEP upregulates Phospho1...

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a master transcriptional cofactor for mitochondrial biogenesis. Mitochondrial intermediate peptidase (MIPEP), a mitochondrial signal peptidase, plays an important role in the maturation and activation of mitochondrial proteins. Caloric restriction has lifespan-extending effects that are reportedly exerted through induced expression of PGC-1α and MIPEP in white adipose tissue. To evaluate how upregulation of PGC-1α and MIPEP contributes to changes in the cellular characteristics of adipocytes, this study examined the mitochondrial function and differentiation of 3T3-L1 preadipocytes with single overexpression (OE) or double OE of Pgc-1α and Mipep. Compared with single-OE cells, double-OE cells exhibited no significant changes in oxygen consumption rate or mitochondrial morphology, but did show increased mitochondrial DNA levels. White adipocyte cell differentiation was suppressed in both Pgc-1α single-OE cells and double-OE cells. Notably, double-OE cells exhibited increased mRNA levels of phosphoethanolamine/phosphocholine phosphatase 1 (Phospho1), which plays a role in phospholipid metabolism and non-canonical thermogenesis. Phospho1 expression was also increased in white adipose tissue of mice under caloric restriction. In summary, the double OE of Pgc-1α and Mipep induced Phospho1 expression and suppressed adipocyte maturation, with little effect on mitochondrial function. This study provides new insights into the mitochondria-related mechanism of caloric restriction in adipocytes.