Figure 2.

Mechanisms of PVAT dysfunction in diet‐induced obesity. HFD‐induced adipocyte hypertrophy leads to hypoxia and the production of pro‐inflammatory cytokines and chemokines, activation of NADPH oxidase and down‐regulation of antioxidant enzymes (e.g. superoxide dismutase and peroxiredoxin‐1) and non‐enzymatic antioxidants (e.g. glutathione). Infiltrating immune cells potentiate PVAT inflammation and oxidative stress. Chronic hyperleptinaemia leads to vascular leptin resistance (loss of leptin‐induced vasodilatation) and potentiation of PVAT inflammation. Long‐term obesity decreases PVAT H₂S production by down‐regulating CSE expression. The up‐regulation of arginases leads to L‐arginine deficiency and eNOS uncoupling (enhanced superoxide production and reduced NO production by eNOS). PVAT adiponectin expression is reduced in obesity, very likely due to a down‐regulation of PPARγ. Normally, NO stimulates adiponectin secretion and adiponectin increases PVAT NO production. This positive feedback mechanism is impaired in obesity.