Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Diabetes and Metabolism Research Center, The Ohio State University, Columbus, OH, United States.
Front Immunol. 2021 Feb 25;12:612496. doi: 10.3389/fimmu.2021.612496. eCollection 2021.
The cardiometabolic syndrome involves a clustering of metabolic and cardiovascular factors which increase the risk of patients developing both Type 2 Diabetes Mellitus and cardio/cerebrovascular disease. Although the mechanistic underpinnings of this link remain uncertain, key factors include insulin resistance, excess visceral adiposity, atherogenic dyslipidemia, and endothelial dysfunction. Of these, a state of resistance to insulin action in overweight/obese patients appears to be central to the pathophysiologic process. Given the increasing prevalence of obesity-related Type 2 Diabetes, coupled with the fact that cardiovascular disease is the number one cause of mortality in this patient population, a more thorough understanding of the cardiometabolic syndrome and potential options to mitigate its risk is imperative. Inherent in the pathogenesis of insulin resistance is an underlying state of chronic inflammation, at least partly in response to excess adiposity. Within obese adipose tissue, an immunomodulatory shift occurs, involving a preponderance of pro-inflammatory immune cells and cytokines/adipokines, along with antigen presentation by adipocytes. Therefore, various adipokines differentially expressed by obese adipocytes may have a significant effect on cardiometabolism. Clusterin is a molecular chaperone that is widely produced by many tissues throughout the body, but is also preferentially overexpressed by obese compared lean adipocytes and relates strongly to multiple components of the cardiometabolic syndrome. Herein, we summarize the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism and discuss potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease.
代谢心血管综合征涉及代谢和心血管因素的聚类，这些因素增加了患者发生 2 型糖尿病和心血管/脑血管疾病的风险。尽管这种联系的机制基础仍不确定，但关键因素包括胰岛素抵抗、内脏脂肪过多、致动脉粥样硬化性血脂异常和内皮功能障碍。在这些因素中，超重/肥胖患者对胰岛素作用的抵抗状态似乎是病理生理过程的核心。鉴于肥胖相关 2 型糖尿病的患病率不断增加，再加上心血管疾病是该患者群体死亡的首要原因，因此更深入地了解代谢心血管综合征及其降低风险的潜在选择至关重要。胰岛素抵抗的发病机制中存在潜在的慢性炎症状态，至少部分是对脂肪过多的反应。在肥胖的脂肪组织中，发生免疫调节转变，涉及大量促炎免疫细胞和细胞因子/脂肪因子，以及脂肪细胞的抗原呈递。因此，肥胖脂肪细胞差异表达的各种脂肪因子可能对代谢心血管产生重大影响。簇蛋白是一种分子伴侣，广泛存在于体内许多组织中，但在肥胖脂肪细胞中过表达，与代谢心血管综合征的多个成分密切相关。在此，我们总结了循环和脂肪细胞特异性簇蛋白在代谢心血管中的已知和潜在作用，并讨论了进一步研究的潜在可能性，以确定簇蛋白是否是减轻代谢和心血管疾病的可行靶点。
