Hormonal
Obesity-induced insulin resistance is mediated by an imbalance in pro- and anti-inflammatory adipokines, where increased pro-inflammatory adipokines (e.g., TNF-α, IL-6, leptin) and decreased anti-inflammatory adipokines (e.g., adiponectin) trigger inflammatory signaling cascades that suppress insulin receptor substrate (IRS) phosphorylation.
In obesity, fat tissue doesn't just store energy; it releases inflammatory signals (adipokines) that block insulin's action. This happens because the balance of these signals shifts towards inflammation (high TNF-alpha, IL-6, leptin) and away from protection (low adiponectin). Addressing insulin resistance requires understanding this inflammatory component, not just caloric intake.
Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines.
Why this rating
The paper is a review of multiple studies in rodents and humans, citing strong mechanistic evidence, though clinical translation of neutralization is noted as controversial.
Source
Adipokines Mediate Inflammation and Insulin Resistance
Hyokjoon Kwon et al. · Frontiers in Endocrinology · 2013
DOI 10.3389/fendo.2013.00071
More from this paper
- Pro-inflammatory adipokines such as TNF-α and IL-6 induce insulin resistance by activating kinases (JNK, IKKβ) that phosphorylate IRS1/2 on serine residues, thereby inhibiting tyrosine phosphorylation and downstream insulin signaling.Strong
- Adipose tissue immune cell composition shifts in obesity from anti-inflammatory (M2 macrophages, Th2 T cells, Tregs) to pro-inflammatory (M1 macrophages, Th1 T cells, CD8+ T cells), driving local and systemic inflammation that contributes to insulin resistance.Good
- Adiponectin, an anti-inflammatory adipokine, improves insulin sensitivity by activating AMPK to enhance fatty acid oxidation and glucose uptake, but its levels are decreased in obesity due to suppression by inflammatory signals.Good
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