Shah Arti, Mehta Nehal, Reilly Muredach P
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
JPEN J Parenter Enteral Nutr. 2008 Nov-Dec;32(6):638-44. doi: 10.1177/0148607108325251.
Adiposity-associated inflammation and insulin resistance are strongly implicated in the development of type 2 diabetes and atherosclerotic cardiovascular disease. This article reviews the mechanisms of adipose inflammation, because these may represent therapeutic targets for insulin resistance and for prevention of metabolic and cardiovascular consequences of obesity. The initial insult in adipose inflammation and insulin resistance, mediated by macrophage recruitment and endogenous ligand activation of Toll-like receptors, is perpetuated through chemokine secretion, adipose retention of macrophages, and elaboration of pro-inflammatory adipocytokines. Activation of various kinases modulates adipocyte transcription factors, including peroxisome proliferator-activated receptor-gamma and NFkappaB, attenuating insulin signaling and increasing adipocytokine and free fatty acid secretion. Inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. Paracrine and endocrine adipose inflammatory events induce a local and systemic inflammatory, insulin-resistant state promoting meta-bolic dyslipidemia, type 2 diabetes, and cardiovascular disease. Developing therapeutic strategies that target both adipose inflammation and insulin resistance may help to prevent type 2 diabetes and cardiovascular disease in the emerging epidemic of obesity.
肥胖相关的炎症和胰岛素抵抗与2型糖尿病及动脉粥样硬化性心血管疾病的发生密切相关。本文综述了脂肪炎症的机制，因为这些机制可能是胰岛素抵抗以及预防肥胖的代谢和心血管后果的治疗靶点。脂肪炎症和胰岛素抵抗的初始损伤由巨噬细胞募集和Toll样受体的内源性配体激活介导，并通过趋化因子分泌、巨噬细胞在脂肪组织中的滞留以及促炎脂肪细胞因子的产生而持续存在。各种激酶的激活调节脂肪细胞转录因子，包括过氧化物酶体增殖物激活受体γ和核因子κB，减弱胰岛素信号传导并增加脂肪细胞因子和游离脂肪酸的分泌。炎症会阻碍脂肪细胞分化，并进一步加剧脂肪功能障碍和炎症。旁分泌和内分泌性脂肪炎症事件会诱发局部和全身性炎症、胰岛素抵抗状态，进而促进代谢性血脂异常、2型糖尿病和心血管疾病。制定针对脂肪炎症和胰岛素抵抗的治疗策略，可能有助于在肥胖这一日益流行的疾病中预防2型糖尿病和心血管疾病。
