Insufficient sleep disrupts glucose metabolism during pregnancy by inhibiting PGC-1α

BACKGROUND: Gestational diabetes mellitus (GDM) impacted about 17 million pregnancies globally and predisposes both the mother and her offspring to metabolic disorders. Insufficient sleep has been shown to be associated with GDM. This study aimed to explore the molecular link between sleep and GDM. METHODS: The sleep of pregnant mice was disturbed with motion a rod and the mice received either dimethyl sulfoxide (DMSO) or ZLN005. Insulin resistance was assessed by intraperitoneal glucose tolerance test (GTT). Adenosine triphosphate (ATP), reactive oxygen species (ROS), and cytokines were measured with respective commercial kits. Gene expression was analyzed with quantitative polymerase chain reaction (qPCR), western blot, and/or immunohistochemistry (IHC). RESULTS: Sleep disturbance increased blood glucose level and insulin resistance, increased ROS and inflammatory cytokines, and reduced ATP level in pregnant mice. The expression levels of PGC-1α and downstream metabolic genes and antioxidant genes in pregnant mouse muscle were inhibited by sleep disturbance. ZLN005 promoted expression of PGC-1α and its target genes, increased muscle ATP level, decreased muscle ROS, and reduced blood glucose level and insulin resistance in sleep disturbed pregnant mice, indicating that PGC-1α played a critical role in sleep insufficiency caused GDM and might be a target for intervention. CONCLUSIONS: PGC-1 was a key player in the sleep disorder GDM and might be a target for treatment.