Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice.

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. Mo

SUBMITTER: Svensson K 

PROVIDER: S-EPMC4970654 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature