| Literature DB >> 30026188 |
Jihyun Kim1, Min Sung Park1, Kyoungsoo Ha1, Chulhong Park1, Jisu Lee1, Randall L Mynatt2, Ji Suk Chang3.
Abstract
Transcriptional coactivator PPAR γ coactivator (PGC)-1α and its splice variant N-terminal (NT)-PGC-1α mediate transcriptional regulation of brown adipose tissue (BAT) thermogenesis in response to changes in ambient temperature. PGC-1α is dispensable for cold-induced BAT thermogenesis as long as NT-PGC-1α is present. However, the functional significance of NT-PGC-1α in BAT has not been determined. In the present study, we generated NT-PGC-1α-/- mice to investigate the effect of NT-PGC-1α deficiency on adaptive BAT thermogenesis. At thermoneutrality, NT-PGC-1α-/- 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-1α-/- BAT. This alteration, in turn, enhanced glucose utilization within the NT-PGC-1α-/- BAT mitochondria. In line with this, NT-PGC-1α-/- mice had higher reliance on carbohydrates. In response to cold or β3-adrenergic receptor agonist, NT-PGC-1α-/- mice transiently exhibited lower thermogenesis but reached similar thermogenic capacities as their WT littermates. Collectively, these findings demonstrate that NT-PGC-1α is an important contributor to the maintenance of FAO capacity in BAT at thermoneutrality and provide deeper insights into the relative contributions of PGC-1α and NT-PGC-1α to temperature-regulated BAT remodeling.Entities:
Keywords: N-terminal peroxisome proliferator-activated receptor gamma coactivator 1-alpha; beta-3 adrenergic receptor; fatty acid; thermogenesis
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Year: 2018 PMID： 30026188 PMCID： PMC6121938 DOI： 10.1194/jlr.M085647
Source DB: PubMed Journal: J Lipid Res ISSN： 0022-2275 Impact factor: 5.922