| First Author | Kim J | Year | 2018 |
| Journal | J Lipid Res | Volume | 59 |
| Issue | 9 | Pages | 1660-1670 |
| PubMed ID | 30026188 | Mgi Jnum | J:264627 |
| Mgi Id | MGI:6197425 | Doi | 10.1194/jlr.M085647 |
| Citation | Kim J, et al. (2018) NT-PGC-1alpha deficiency decreases mitochondrial FA oxidation in brown adipose tissue and alters substrate utilization in vivo. J Lipid Res 59(9):1660-1670 |
| abstractText | Transcriptional coactivator PPAR gamma coactivator (PGC)-1alpha and its splice variant N-terminal (NT)-PGC-1alpha mediate transcriptional regulation of brown adipose tissue (BAT) thermogenesis in response to changes in ambient temperature. PGC-1alpha is dispensable for cold-induced BAT thermogenesis as long as NT-PGC-1alpha is present. However, the functional significance of NT-PGC-1alpha in BAT has not been determined. In the present study, we generated NT-PGC-1alpha(-/-) mice to investigate the effect of NT-PGC-1alpha deficiency on adaptive BAT thermogenesis. At thermoneutrality, NT-PGC-1alpha(-/-) mice exhibited abnormal BAT phenotype with increased accumulation of large lipid droplets concomitant with marked downregulation of FA oxidation (FAO)-related genes. Consistent with transcriptional changes, mitochondrial FAO was significantly diminished in NT-PGC-1alpha(-/-) BAT. This alteration, in turn, enhanced glucose utilization within the NT-PGC-1alpha(-/-) BAT mitochondria. In line with this, NT-PGC-1alpha(-/-) mice had higher reliance on carbohydrates. In response to cold or beta3-adrenergic receptor agonist, NT-PGC-1alpha(-/-) mice transiently exhibited lower thermogenesis but reached similar thermogenic capacities as their WT littermates. Collectively, these findings demonstrate that NT-PGC-1alpha is an important contributor to the maintenance of FAO capacity in BAT at thermoneutrality and provide deeper insights into the relative contributions of PGC-1alpha and NT-PGC-1alpha to temperature-regulated BAT remodeling. |
