Hormonal
Chronic inflammation driven by macrophage infiltration into white adipose tissue (WAT) is a primary causal mechanism for obesity-induced insulin resistance, rather than merely a correlative symptom.
In obesity, fat tissue becomes inflamed due to macrophage infiltration, which actively blocks insulin from working properly. This is a biological defense mechanism, not just a passive result of having extra fat. Treating the underlying inflammation (e.g., via medications like TZDs shown in the study) may improve insulin sensitivity independently of immediate weight loss.
These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance. We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue.
Why this rating
High-quality mechanistic evidence using multiple genetic and diet-induced mouse models with temporal tracking showing inflammation precedes hyperinsulinemia.
Source
Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
Haiyan Xu et al. · Journal of Clinical Investigation · 2003
DOI 10.1172/jci19451
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