Obesity-Related Alterations in Cardiac Lipid Profile and Nondipping Blood Pressure Pattern during Transition to Diastolic Dysfunction in Male db/db Mice
Obesity-Related Alterations in Cardiac Lipid Profile and Nondipping Blood Pressure Pattern during Transition to Diastolic Dysfunction in Male db/db Mice
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DOI：
10.1210/en.2012-1835
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发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Sowers, James R.
中科院分区：
文献类型：
--
作者：
DeMarco, Vincent G.;Ford, David A.;Sowers, James R.
肥胖和非下降的昼夜血压（BP）模式与舒张功能障碍有关。异位脂质积聚是一种重要的代谢异常，可导致心脏舒张功能障碍。然而，鲜为人知的是，不同的脂质和脂质分析物的组成舒张功能障碍的贡献。我们进行了功能和结构的研究，并分析了心脏脂质分布在两个时间点的进展，舒张功能障碍的肥胖遗传模型。肥胖雄性db/db小鼠12 ~ 15周龄的心脏磁共振成像和血压遥测显示，12周龄时血压昼夜节律模式和舒张功能正常，15周龄时血压昼夜节律模式和舒张功能开始恶化。脂质组学分析表明，12周时db/db的脂肪酸和神经酰胺水平升高，但在15周时其水平降低，这是伴随着持续的线粒体超微结构异常，与脂肪酸氧化增加和活性氧产生增加的证据相一致。三酰甘油和二酰甘油水平升高，在12和15周，但他们的组成改变，包括更多的饱和和不饱和脂肪酰基在15周。在两个时间点，脂滴明显增加，这与磷脂酰胆碱增加相关。总之，一种独特的心肌脂质重塑模式，伴随着氧化应激，与肥胖，胰岛素抵抗db/db小鼠舒张功能障碍的发病相关。（内分泌学154：159-171，2013）
Obesity and a nondipping circadian blood pressure (BP) pattern are associated with diastolic dysfunction. Ectopic lipid accumulation is increasingly recognized as an important metabolic abnormality contributing to diastolic dysfunction. However, little is known about the contribution of different lipids and the composition of lipid analytes to diastolic dysfunction. We have performed functional and structural studies and analyzed cardiac lipid profile at two time points during progression to diastolic dysfunction in a genetic model of obesity. Serial cardiac magnetic resonance imaging and telemetric measures of BP between 12 and 15 wk of age in obese male db/db mice indicated a nondipping circadian BP pattern and normal diastolic function at 12 wk that progressed to a deteriorating nondipping pattern and onset of diastolic dysfunction at 15 wk of age. Lipidomic analysis demonstrated elevated fatty acids and ceramides in db/db at 12 wk, but their levels were decreased at 15 wk, and this was accompanied by persistent mitochondrial ultrastructural abnormalities in concert with evidence of increased fatty acid oxidation and enhanced production of reactive oxygen species. Triacylglyceride and diacylglyceride levels were elevated at both 12 and 15 wk, but their composition changed to consist of more saturated and less unsaturated fatty acyl at 15 wk. An increase in the lipid droplets was apparent at both time points, and this was associated with increases in phosphatidycholine. In conclusion, a distinct pattern of myocardial lipid remodeling, accompanied by oxidative stress, is associated with the onset of diastolic dysfunction in obese, insulin-resistant db/db mice. (Endocrinology 154: 159-171, 2013)