The dysregulated adipose tissue: a connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis.
An emerging paradigm supports the view that adipose tissue (AT) dysregulation might play a crucial role in the pathogenesis of insulin-resistance and atherosclerosis. The net result of such a dysregulation is a state of low-grade, chronic, systemic inflammation that, in turn, links both the metabolic and the vascular pathologies. Overwhelming evidence shows that high circulating levels of markers of chronic inflammation predict the development of T2DM and atherosclerotic manifestations. Therefore, atherosclerotic cardiovascular disease and T2DM seem to arise from a "common soil", and chronic inflammation is a candidate. In this scenario, the dysfunctional AT provide a common hallmark for these apparently divergent disorders. An important question then is whether dysregulated and inflamed AT can be converted to healthy fat and, consequently, the development or the progression of metabolic and vascular impairment can be prevented or reversed by the modulation of the inflammatory profile. The beneficial effects of weight loss on obesity-related complications are clearly associated with the modification of the inflammatory profile in the AT. Furthermore, the thiazolidinediones (TZDs) possess both anti-inflammatory and anti-atherogenic properties. Intriguingly, in contrast to the paradoxical weight gain, TZDs influence favorably the pattern of adipokines. In conclusion, accepting the paradigm of AT dysfunction, the use of TZDs will represent an additional therapeutic approach that, in association with lifestyle interventions, would improve inflammation, ameliorate insulin sensitivity, and alleviate the related risk of atherosclerosis.
Murdolo
Giuseppe
G
Department of Internal Medicine, Division of Endocrine and Metabolic Sciences, Perugia University, Perugia, Italy. giuseppe.murdolo@medic.gu.se
Smith
Ulf
U
D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications; D007333:Insulin Resistance; D045162:Thiazolidinediones / Q000494:pharmacology*; D015431:Weight Loss / Q000502:physiology
D045162:Thiazolidinediones