Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning.
Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning.
复制标题
DOI：
10.1371/journal.pone.0024068
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shankar K
中科院分区：
文献类型：
--
作者：
Borengasser SJ;Lau F;Kang P;Blackburn ML;Ronis MJ;Badger TM;Shankar K
在子宫内暴露于母体肥胖会增加后代在以后的生活中患肥胖症的风险。我们以前也曾报道过，肥胖大鼠母鼠的后代在出生后第21天（PND）发生肝脂肪变性、轻度高胰岛素血症和肝脏中的脂肪生成基因特征。在本研究中，我们检查了在PND 21时来自瘦和肥胖母鼠的雄性Sprague-Dawley后代的全身和肝脏适应。间接热量测定法显示能量消耗减少（p<0.001）和RER值增加（p<0.001），高脂肪饮食（45%千卡来自脂肪）消耗进一步加剧了这一情况，表明通过PRCF分析，肥胖母鼠后代利用脂肪酸的能力受损。已知线粒体功能与肝脏中的脂肪酸氧化（FAO）相关。肥胖母鼠的后代肝脏线粒体功能的几个标志物降低。这些指标包括SIRT 3 mRNA（p = 0.012）和线粒体蛋白含量（p = 0.002）、电子传递链复合物（II、III和ATP酶）和空腹PGC-1α mRNA表达（p<0.001）。 此外，肝脏LCAD（SIRT 3靶标）不仅降低2倍（p<0.001），而且在肥胖母鼠的后代中也被过度乙酰化（p<0.005），表明肝脏FAO降低。总之，暴露于母体肥胖有助于全身和肝脏能量代谢的早期扰动。线粒体功能障碍可能是降低肝脂肪酸氧化的潜在事件，并且在有害的肥胖相关共病如胰岛素抵抗和NAFLD的发展之前。
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-1α 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.
登录
查看更多内容
DOI：
10.1152/ajpregu.00549.2009
发表时间：
2010-10-01
影响因子：
2.8
作者：
Jackman, Matthew R.;MacLean, Paul S.;Bessesen, Daniel H.
通讯作者：
Bessesen, Daniel H.
DOI：
10.1152/ajpregu.00310.2010
发表时间：
2010-09-01
影响因子：
2.8
作者：
Heerwagen, Margaret J. R.;Miller, Melissa R.;Friedman, Jacob E.
通讯作者：
Friedman, Jacob E.
影响因子：
7.4
作者：
Bao, Jianjun;Scott, Iain;Lu, Zhongping;Pang, Liyan;Dimond, Christopher C.;Gius, David;Sack, Michael N.
通讯作者：
Sack, Michael N.
影响因子：
4.3
作者：
Hayashida, Satoru;Arimoto, Akie;Soeda, Shinji
通讯作者：
Soeda, Shinji
影响因子：
3.8
作者：
Divi, Rao L.;Einem, Tracey L.;Poirier, Miriam C.
通讯作者：
Poirier, Miriam C.