Hypothalamic JNK1 and IKKβ activation and impaired early postnatal glucose metabolism after maternal perinatal high-fat feeding

摘要: Hypothalamic inflammation has been demonstrated to be an important mechanism in the pathogenesis of obesity-induced type 2 diabetes mellitus. Feeding pregnant and lactating rodents a diet rich saturated fatty acids consistently shown predispose offspring for development obesity impaired glucose metabolism. However, hypothalamic not addressed as potential underlying mechanism. In this study, virgin female C57BL/6 mice received high-fat feeding starting at conception until weaning postnatal d 21. The developed increased body weight, fat content, serum leptin concentrations during nursing period. Analysis tissue 21 showed up-regulation several members toll-like receptor 4 signaling cascade subsequent activation c-Jun N-terminal kinase 1 IκB kinase-β inflammatory pathways. Interestingly, tolerance testing revealed signs along with hepatic expression key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. addition, significantly pancreatic PGC1α suggests role sympathetic innervation mediating effects periphery. Taken together, our data indicate early intolerance after maternal perinatal feeding.