Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice.
FASEB J
; 30(5): 1976-86, 2016 05.
Article
em En
| MEDLINE
| ID: mdl-26849960
ABSTRACT
Ketone bodies (KBs) are crucial energy substrates during states of low carbohydrate availability. However, an aberrant regulation of KB homeostasis can lead to complications such as diabetic ketoacidosis. Exercise and diabetes affect systemic KB homeostasis, but the regulation of KB metabolism is still enigmatic. In our study in mice with either knockout or overexpression of the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α in skeletal muscle, PGC-1α regulated ketolytic gene transcription in muscle. Furthermore, KB homeostasis of these mice was investigated during withholding of food, exercise, and ketogenic diet feeding, and after streptozotocin injection. In response to these ketogenic stimuli, modulation of PGC-1α levels in muscle affected systemic KB homeostasis. Moreover, the data demonstrate that skeletal muscle PGC-1α is necessary for the enhanced ketolytic capacity in response to exercise training and overexpression of PGC-1α in muscle enhances systemic ketolytic capacity and is sufficient to ameliorate diabetic hyperketonemia in mice. In cultured myotubes, the transcription factor estrogen-related receptor-α was a partner of PGC-1α in the regulation of ketolytic gene transcription. These results demonstrate a central role of skeletal muscle PGC-1α in the transcriptional regulation of systemic ketolytic capacity.-Svensson, K., Albert, V., Cardel, B., Salatino, S., Handschin, C. Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dieta Cetogênica
/
Privação de Alimentos
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Homeostase
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Corpos Cetônicos
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Atividade Motora
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Suíça