Why Does Obesity Increase the Risk for Cardiovascular Disease?
Why Does Obesity Increase the Risk for Cardiovascular Disease?
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DOI：
10.2174/1381612811319320003
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
Salehi, Sajad
中科院分区：
文献类型：
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作者：
Boden, Guenther;Salehi, Sajad
胰岛素抵抗和炎症被认为是肥胖和心血管疾病 (CVD) 之间的重要联系。血浆游离脂肪酸（FFA），无论是从异常增大的脂肪组织中释放出来，还是作为过量营养摄入的一部分，都会产生胰岛素抵抗和炎症。胰岛素抵抗和炎症都与一些独立的 CVD 危险因素密切相关，例如 2 型糖尿病 (T2DM)、高血压、血脂异常和凝血障碍。已经提出了几种假设来解释血浆 FFA 水平升高如何导致胰岛素抵抗，包括 a) 脂质代谢假说、b) 炎症假说、c) 高胰岛素血症假说和 d) 内质网 (ER) 应激假说。后者不需要血浆 FFA 水平升高，因此提供了一种机制来解释所有肥胖个体（即血浆 FFA 水平升高和不升高的个体）中胰岛素抵抗和炎症的发生。根据流行病学研究，高胰岛素血症本身被怀疑会导致 CVD，这些研究将慢性高胰岛素血症与 CVD 相关联，但尚未建立因果关系。然而，有新的结果支持这样的假设：慢性高胰岛素血症本身可以促进 CVD 的发展。例如，高胰岛素血症可以激活甘油三酯的形成、几种基质金属蛋白酶（MMP）和凝血的组织因子途径，所有这些都已知与CVD相关，即使存在“代谢性胰岛素抵抗”。
Insulin resistance and inflammation are recognized as important links between obesity and cardiovascular disease (CVD). Plasma free fatty acids (FFA), either released from the abnormally enlarged adipose tissue or as part of the excessive nutrient intake, produce insulin resistance and inflammation. Both insulin resistance and inflammation are tightly linked to several independent CVD risk factors such as type 2 diabetes (T2DM), hypertension, dyslipidemia and disorders of blood coagulation. Several hypotheses have been proposed to explain how increased plasma FFA levels can cause insulin resistance including a) the lipid metabolite hypothesis, b) the inflammation hypothesis, c) the hyperinsulinemia hypothesis and d) the endoplasmic reticulum (ER) stress hypothesis. The latter does not require presence of elevated plasma FFA levels and thus provides a mechanism to explain the development of insulin resistance and inflammation in all obese individuals, i.e., those with and without elevated plasma FFA levels.Hyperinsulinemia per se has been suspected to cause CVD based on epidemiologic studies which have associated chronic hyperinsulinemia with CVD without, however, establishing a cause and effect relationship. There are, however, newer results which support the hypothesis that chronic hyperinsulinemia per se can promote the development of CVD. For instance, hyperinsulinemia can activate triglyceride formation, several matrix metalloproteinases (MMP), and the tissue factor pathway of blood coagulation, all of which are known to be associated with CVD, even in the presence of "metabolic insulin resistance".