Figure 1

a | In the lean state, small adipocytes efficiently store fatty acids as triglyceride (TG input, arrow), which can be mobilized and used to generate ATP through the mitochondrial β-oxidation pathway in muscle during periods of caloric need. Insulin-stimulated glucose uptake under these conditions is normal. b | Excess caloric intake leads to metabolic overload, increased TG input and adipocyte enlargement. Nonetheless, in non-diabetic overweight individuals, TG storage by adipose cells and β-oxidation in muscle can often be maintained to prevent insulin resistance. c | On further overloading with TG, hypertrophy of adipocytes and increased secretion of macrophage chemoattractants occurs, including the secretion of monocyte chemoattractant protein-1 (MCP-1; arrows), which recruits additional macrophages. d | Macrophage recruitment in turn results in a pro-inflammatory state in obese adipose tissue. Infiltrating macrophages secrete large amounts of tumour-necrosis factor-α (TNFα), which results in a chronic inflammatory state with impaired TG deposition and increased lipolysis (arrow and plus signal). The excess of circulating TG and free fatty acids results in the accumulation of activated lipids in the muscle (yellow dots), disrupting functions such as mitochondrial oxidative phosphorylation and insulin-stimulated glucose transport, thus triggering insulin resistance.