Division of Endocrinology, Diabetes, Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Curr Opin Endocrinol Diabetes Obes. 2011 Apr;18(2):139-43. doi: 10.1097/MED.0b013e3283444b09.
To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people.
Elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. Insulin resistance is clinically important because it is closely associated with several diseases including type 2 diabetes, hypertension, dyslipidemia and abnormalities in blood coagulation and fibrinolysis. These disorders are all independent risk factors for cardiovascular disease (heart attacks, strokes and peripheral arterial disease). The mechanisms by which FFA can cause insulin resistance, although not completely known, include generation of lipid metabolites (diacylglycerol), proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP1) and cellular stress including oxidative and endoplasmic reticulum stress.
Increased plasma FFA levels are an important cause of obesity-associated insulin resistance and cardiovascular disease. Therapeutic application of this knowledge is hampered by the lack of readily accessible methods to measure FFA and by the lack of medications to lower plasma FFA levels.
描述游离脂肪酸(FFA)在肥胖人群胰岛素抵抗中的作用。
在患有 2 型糖尿病的肥胖患者中,血浆 FFA 水平升高可导致很大一部分胰岛素抵抗。胰岛素抵抗具有重要的临床意义,因为它与多种疾病密切相关,包括 2 型糖尿病、高血压、血脂异常以及血液凝固和纤维蛋白溶解的异常。这些疾病都是心血管疾病(心脏病发作、中风和外周动脉疾病)的独立危险因素。尽管 FFA 导致胰岛素抵抗的确切机制尚不完全清楚,但包括脂质代谢物(二酰基甘油)、促炎细胞因子(TNF-α、IL-1β、IL-6、MCP1)和细胞应激(包括氧化应激和内质网应激)的产生。
血浆 FFA 水平升高是肥胖相关胰岛素抵抗和心血管疾病的一个重要原因。由于缺乏易于测量 FFA 的方法以及降低血浆 FFA 水平的药物,因此该知识的治疗应用受到阻碍。