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• W1988773742 abstract "Obesity and type 2 diabetes are worldwide health issues. The present paper investigates prenatal and postnatal pathways to obesity, identifying different metabolic outcomes with different effects on insulin sensitivity and different underlying mechanisms involving key components of insulin receptor signaling pathways. Pregnant Wistar rats either were fed chow ad libitum or were undernourished throughout pregnancy, generating either control or intrauterine growth restricted (IUGR) offspring. Male offspring were fed either standard chow or a high-fat diet from weaning. At 260 d of age, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and other metabolic parameters were measured. As expected, high-fat feeding caused diet-induced obesity (DIO) and insulin resistance. Importantly, the insulin sensitivity of IUGR offspring was similar to that of control offspring, despite fasting insulin hypersecretion and increased adiposity, irrespective of postnatal nutrition. Real-time PCR and Western blot analyses of key markers of insulin sensitivity and metabolic regulation showed that IUGR offspring had increased hepatic levels of atypical protein kinase C ζ (PKC ζ) and increased expression of fatty acid synthase mRNA. In contrast, DIO led to decreased expression of fatty acid synthase mRNA and hepatic steatosis. The decrease in hepatic PKC ζ with DIO may explain, at least in part, the insulin resistance. Our data suggest that the mechanisms of obesity induced by prenatal events are fundamentally different from those of obesity induced by postnatal high-fat nutrition. The origin of insulin hypersecretion in IUGR offspring may be independent of the mechanistic events that trigger the insulin resistance commonly observed in DIO." @default.
• W1988773742 created "2016-06-24" @default.
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• W1988773742 date "2007-05-01" @default.
• W1988773742 modified "2023-10-17" @default.
• W1988773742 title "Prenatal and Postnatal Pathways to Obesity: Different Underlying Mechanisms, Different Metabolic Outcomes" @default.
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• W1988773742 doi "https://doi.org/10.1210/en.2006-1641" @default.
• W1988773742 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17272392" @default.
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