Maternal Overweight Programs Offspring Insulin and Adiponectin Signaling

Abstract

Maternal overweight (OW) was induced in rats by overfeeding via total enteral nutrition. Male offspring from OW dams gained greater (p < 0.005) body weight and %fat mass assessed by NMR, X‐ray CT and adipose tissue weights when fed high fat diet (45% fat). Hepatic microarray analyses at postnatal day 21 revealed 147 transcripts were significantly (±1.8‐fold, p < 0.05) altered by maternal OW, including expression of 20 known SREBP‐1‐regulated transcripts. Expression of SREBP‐1 mRNA and lipogenic transcripts was confirmed using real‐time PCR. Increased nuclear levels of SREBP‐1 and recruitment to the FASN promoter were confirmed via ELISA and ChIP analyses, respectively. Decreased expression of 10 PPARα regulated genes including FGF21 was also uncovered. FGF21 serum levels were lower (p< 0.05) in OW dam offspring. Further serum levels of high mol wt adiponectin (p < 0.05) were decreased in OW dam offspring at weaning. While no changes in %fat mass or adipose tissue adiponectin mRNA were observed, hepatic expression of AdipoR1 and R2 were lower in OW dam offspring. Finally, phosphorylation of the adiponectin target AMPK was significantly decreased in livers of OW dam offspring. Our data suggest that maternal OW at conception leads to increased lipogenic gene expression in concert with decreased PPARα‐adiponectin‐AMPK signaling in the liver of young offspring. Support ARS‐CRIS 6251‐51000‐005‐00D and R01‐DK084225.