Location: Location not imported yet.Title: Gestational exposure to maternal obesity decreases mitochondrial SIRT3 and components of oxidative phosphorylation in offspring liver) Author
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract only
Publication Acceptance Date: 12/15/2010
Publication Date: 4/1/2011
Citation: Borengasser, S., Ronis, M.J., Badger, T.M., Shankar, K. 2011. Gestational exposure to maternal obesity decreases mitochondrial SIRT3 and components of oxidative phosphorylation in offspring liver [abstract]. Proceedings of the Federation of americcan Societies for Experimental Biology Conference. 25(Meeting Abstracts):990.11. Interpretive Summary: The body composition of the mother at conception and during pregnancy has long-term consequences for the health of the offspring. Using a model of obesity in the rat, we have previously shown that, maternal obesity via metabolic factors independent of genetic influences leads to increased risk of obesity in the offspring when challenged with a high fat diet. In the present studies we investigated whole body and liver metabolism in offspring from lean and obese dams at weaning. We measured energy expenditure, fuel utilization, and mitochondrial proteins. Our results suggest that mitochondrial dysfunction may precede the development of metabolic abnormalities and obesity-related diseases in offspring from obese dams at weaning.
Technical Abstract: Exposure to maternal overweight (OW) during development influences the risk of obesity in adult-life. We reported that by postnatal day (PND) 120 male offspring from OW rat dams have greater body weight and fat mass (p<0.005), and develop insulin resistance when fed high-fat diets (HFD, 45% fat). OW dam offspring develop hepatic steatosis and lipogenic gene expression signature at PND21, prior to obesity. Here we examined systemic and hepatic metabolic adaptations in offspring from lean and OW dams at PND21. Offspring from OW dams had decreased energy expenditure (p<0.05) and higher respiratory exchange ratio (RER) values (p<0.05) on AIN-93G diet. HFD consumption further exacerbated the decrease in EE and RER as compared to offspring of lean dams, indicating an impaired capacity to utilize fatty acids(FA). Mitochondrial function in the liver is an important regulator of FA utilization. Liver protein content of electron transport chain complexes (II, III, and ATPase) was decreased (p<0.03) in offspring from OW dams. Hepatic mRNA and protein expression of SIRT3, an important epigenetic regulator of mitochondrial oxidative capacity was decreased (p<0.002) in offspring from OW dams. In conclusion, mitochondrial dysfunction may precede the development of energy utilization perturbations, hepatic steatosis, adiposity, and insulin resistance in offspring from OW rat dams at weaning.