|BORRENGASSER, SARAH - Arkansas Children'S Nutrition Research Center (ACNC)|
|LAU, FRANCHESCA - Arkansas Children'S Nutrition Research Center (ACNC)|
|KANG, PING - Arkansas Children'S Nutrition Research Center (ACNC)|
|BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)|
|RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)|
|SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2011
Publication Date: 8/29/2011
Citation: Borrengasser, S.J., Lau, F., Kang, P., Blackburn, M.L., Ronis, M.J., Badger, T.M., Shankar, K. 2011. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning. PLoS One. 6(8):e24068. doi:10.1371/journal.pone.0024068.
Interpretive Summary: There is a rise in the number of pregnant mothers who are overweight or obese. Obesity in children is also on the rise and is beginning at younger ages, even as young as infants. This occurrence of early onset obesity coupled with obese mom suggest, that the environment the fetus is developing in during pregnancy may be contributing to the obesity epidemic. Using a rat model, we have previously shown that maternal obesity prior to conception leads to the development of obesity-related diseases such as mild insulin resistance, fatty liver, and increased ability to store fat in offspring at weaning as compared to offspring of lean rat dams. 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. We found that offspring of obese dams had decreased energy expenditure indicating decreased efficiency to burn kcals for energy. Further, obese dam offspring were also less able to utilize fat for energy which increases the likelihood for fat storage in tissue such as the liver. Mitochondria are sites for fatty burning to take place and we found the proteins that are directly or indirectly involved in using fat for energy were impaired. Taken together, our results suggest that defects in mitochondria may precede the development of metabolic abnormalities and obesity-related diseases in offspring from obese dams at weaning.
Technical Abstract: In utero exposure to maternal obesity increases the offspring’s risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND) 21. In the current study, we examined systemic and hepatic adaptations in male Sprague-Dawley offspring from lean and obese dams at PND21. Indirect calorimetry revealed decreases in energy expenditure (p < 0.001) and increases in RER values (p < 0.001), which were further exacerbated by high fat diet (45% kcals from fat) consumption indicating an impaired ability to utilize fatty acids in offspring of obese dams as analyzed by PRCF. Mitochondrial function is known to be associated with fatty acid oxidation (FAO) in the liver. Several markers of hepatic mitochondrial function were reduced in offspring of obese dams. These included SIRT3 mRNA (p = 0.012) and mitochondrial protein content (p = 0.002), electron transport chain complexes (II, III, and ATPase), and fasting PGC-1 alpha mRNA expression (p < 0.001). Moreover, hepatic LCAD, a SIRT3 target, was not only reduced 2-fold (p < 0.001), but was also hyperacetylated in offspring of obese dams (p < 0.005) suggesting decreased hepatic FAO. In conclusion, exposure to maternal obesity contributes to early perturbations in whole body and liver energy metabolism. Mitochondrial dysfunction may be an underlying event that reduces hepatic fatty acid oxidation and precedes the development of detrimental obesity associated co-morbidities such as insulin resistance and NAFLD.