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Gestational Exposure to Maternal Obesity Decreases Mitochondrial SIRT3 and Components of Oxidative Phosphorylation in Offspring Liver
Author(s) -
Borengasser Sarah J,
Ronis Martin J,
Badger Thomas M,
Shankar Kartik
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.990.11
Subject(s) - offspring , endocrinology , medicine , steatosis , insulin resistance , biology , weaning , overweight , obesity , pregnancy , genetics
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. Support NIHR01‐ DK084225