Stadler Julia T, Lackner Sonja, Mörkl Sabrina, Trakaki Athina, Scharnagl Hubert, Borenich Andrea, Wonisch Willibald, Mangge Harald, Zelzer Sieglinde, Meier-Allard Nathalie, Holasek Sandra J, Marsche Gunther
Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
Division of Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz, Heinrichstraße 31a, 8010 Graz, Austria.
Biomedicines. 2021 Feb 27;9(3):242. doi: 10.3390/biomedicines9030242.
Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight ( = 26), overweight ( = 22), and obese ( = 20) women.
Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women.
Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.
肥胖会增加冠心病风险，部分原因是其与致动脉粥样硬化性血脂异常密切相关，这种血脂异常的特征是甘油三酯水平高和高密度脂蛋白（HDL）胆固醇水平低。HDL的功能受损可能会导致心血管死亡率增加，但肥胖对HDL的组成、结构和功能的影响尚不清楚。设计与方法：我们测定了相对年轻的正常体重（n = 26）、超重（n = 22）和肥胖（n = 20）女性的HDL组成、HDL亚类分布、HDL功能参数以及参与脂蛋白重塑的最重要酶的活性，包括卵磷脂胆固醇酰基转移酶（LCAT）和胆固醇酯转运蛋白（CETP）。
肥胖（体重指数（BMI）≥30）与LCAT和CETP活性的显著变化以及HDL组成改变有关，如载脂蛋白A-I、胆固醇和磷脂含量降低，而促炎性HDL血清淀粉样蛋白a含量增加。我们观察到肥胖时HDL亚类明显向较小的亚类转变，这与血清较低的抗氧化能力有关。LCAT活性、HDL亚类分布和HDL胆固醇与可溶性瘦素受体、脂联素和肝酶活性有关。值得注意的是，这些改变大多仅见于肥胖女性，而不见于超重女性。
肥胖显著影响与肝脏和脂肪组织变化相关的HDL代谢、组成和亚类分布。HDL功能障碍可能导致肥胖人群心血管风险增加。
