Regulation Of PGC-1α And PGC-1β Expression And Its Relation To Mitochondrial Development

The disorder of energy metabolism results to obese, which leads to many diseases. So it is critical to elucidate how to control fat disposition. The mitochondrial apparatus is a fundamental aspect of white fat, where several important cellular functions occur, including amino acid biosynthesis and fatty acid oxidation (FAO). Although the process of adipogenesis, defined as the accumulation of lipid, Indeed, 3T3–L1 preadipocyte differentiation is accompanied by distinctly increased mitochondrial mass. But till now, it's not clear which transcriptional factors and coactivators regulate the mitochondrial biogenesis in adipogenesis in adipocyte. Study showed that Peroxisome proliferator- activated receptorγcoactivator (PGC)-1αandβare coactivators of nuclear receptors and other transcription factors that regulates several components of energy metabolism, particularly hepatic gluconeogenesis, and mitochondrial biogenesis. It is remains unclear whether PGC-1αand PGC-1βrelated to the mitochondrial biogenesis in adipocyte. Moreover , porcine preadipocytes are a better model for the study of obesity and its related disorders, because porcine possess higher lipogenic capacity and similar lipogenic patterns to human adipocytes. But till now, there is no literature about the study of porcine adipocyte mitochondrial available.In the study, we have checked the change of PGC-1αand PGC-1βmRNA expression, mitochondrial mass and oxidative capacity during preadipocyte differentiation. Besides this, the role of leptin and T3 in regulating preadipocyte proliferation, differentiation and mitochondrial development was examined. Lastly, PGC-1βsiRNA was to determine the role of PGC-1βin mitochondrial development in adipocyte. The results are as follows:1. Porcine preadipocyte differentiation was accompanied by not only lipid accumulation but also an distinctly increased mitochondrial mass. Thickly packed mitochondria were seen surrounding the fat globules and nucleus of the differentiated cells, whereas preadipocyte mitochondria displayed a stringlike appearance and were less dense.2. The COX activity , Cyt c protein expression and the mRNA expression of Cyt c, CPT1 and MDH increased with the differentiation of preadipocyte. Decreased UCP2 expression and a low steady UCP3 expression was observed during preadipocyte differentiation. These results suggested cells oxidative capacity increased with differentiation.3. PGC-1αare preferentially expressed in mitochondria-rich tissue with high oxidative capacity, such as heart, skeletal muscle, and liver , and very low expression in WAT.The expression level of PGC-1a in preadipocytes and differentiated adipocytes was low and had no significance difference between them, but increased PGC-1βmRNA with adipocyte differentiation.4. leptin(10-100ng/ml) markedly enhanced the COX activity and the mRNA expression of PGC-1α, PGC-1β,Cytc , CPT1, UCP2 and UCP3 in adipocyte , which play an important role in fatty acid oxidative and energy consume .5. leptin(10-100ng/ml)induced porcine preadipocyte proliferation and had no effect on differentiation. The expression of LPL was increased by leptin, but no change in C/EBPααand PPARγmRNA.6. T3(10-1000nM) markedly enhanced the COX activity and the mRNA expression of PGC-1α, PGC-1β,Cytc , CPT1, COX, MDH, UCP2 and UCP3 in adipocyte, which play an important role in mitochondrial biogenesis and oxidative capacity.7. T3(10-1000nM) stimulated porcine preadipocyte differentiation and no effect on proliferation. The expression of PPARγwas increased by T3 , but no change in C/EBPαand LPL mRNA expression.8. The mRNA expression of CPT1 and COX decreased distinctly, and Cyt c mRNA and COX enzyme activity tend to decrease but not significant by PGC-1βsiRNA which PGC-1βmRNA decreased 40%.Above all, This study showed that the adipogenesis in porcine adipocyte was accompanied by not only lipid accumulation but also an distinctly increased mitochondrial mass and oxidative capacity, which suggest mitochondrial not only function as a fatty acid oxidation apparatus but also play a critical role in adipogenesis in porcine adipocyte. The expression level of PGC-1αin preadipocytes and differentiated adipocytes was low and had no significance difference between them, but PGC-1βmRNAs were markedly induced during adipocyte differentiation, and PGC-1βsiRNA showed mitochondrial development tended to decrease. Thus mitochondrial biogenesis in preadipocyte differentiation may be attribute to PGC-1βor other as-yet-unknown transcriptional coactivators but not PGC-1α. Moreover,The mRNA expression of PGC-1αand PGC-1β, and mitochondrial oxidative capacity markedly increased by leptin and T3, that suggests leptin and T3 maybe regulate mitochondrial development trough inducing PGC-1αand PGC-1β.