Figure 4.

The expansion of adipose tissue leads to adipocyte hypertrophy in obesity. The release of che mokines that induce recruitment of macrophages from the bloodstream increases infiltration and inflammation with enhanced production of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α) and IL-6. This is accomplished by increased release of FFA and dysregulated secretion of leptin, adiponectin and resistin. The macrophage and adipose tissue-derived adipokines acts in a paracrine or autocrine way, which exacerbates adipose tissue inflammation. Altered adipokine secretion, at the systemic level, can lead to decreased muscle and liver insulin sensitivity through enhanced ectopic lipid deposition and inflammation. These effects lead to increased liver glucose production (by means of gluconeogenesis and glycogenolysis). In contrast, muscle metabolism is reshuffled to a pattern of low glucose uptake and low FFA oxidation (with increases in levels of glycerol substrate for liver gluconeogenesis). These events lead to an increase of plasma glucose and, subsequently, an increase of insulin resistance. Adapted from: Galic S et al., 2010