NT-PGC-1α deficiency decreases mitochondrial FA oxidation in brown adipose tissue and alters substrate utilization in vivo.
J Lipid Res
; 59(9): 1660-1670, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30026188
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 ß3-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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Marrom
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Ácidos Graxos
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Mitocôndrias
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Laos