Prenatal High-Salt Diet–Induced Metabolic Disorders via Decreasing Peroxisome Proliferator–Activated Receptor Gamma Coactivator 1α in Adult Male Rat Offspring

Scope: Although prenatal high-salt (HS) intake leads to physiological complications in the offspring, little is known regarding its effects on the offspring's glucose metabolism. Therefore, the objectives of this study are to determine the consequences of prenatal HS diet on the offspring's metabolism and to test a potential therapy. Methods and Results: Pregnant rats are fed either a normal-salt (1% NaCl) or high-salt (8% NaCl) diet during the whole pregnancy. Experiments are conducted in five-month-old male offspring. It is found that the prenatal HS diet reduced the glucose tolerance and insulin sensitivity of the offspring. Additionally, there is down-regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a/PPARGC1A) at the transcript and protein level, which leads to decreased mitochondrial biogenesis and oxidative respiration in skeletal muscle. Moreover, the down-regulation of Ppargc1a is accompanied by decreases in the expression of glucose transporter type 4 (Glut4). With endurance exercise training, these changes are mitigated, which ultimately resulted in improved insulin resistance. Conclusion: These findings suggest that prenatal HS intake induces metabolic disorders via the decreased expression of Ppargc1a in the skeletal muscle of adult offspring, providing novel information concerning the mechanisms and early prevention of metabolic diseases of fetal origins.