Lipid links inflammation, immunity and insulin resistance to cause epidemic diabetes

Incidence of type 2 diabetes (T2D) is dramatically increasing in the past few decades and presently affecting more than 350 million people all over the globe. Oversupply of lipid is one of the major forces behind T2D. Excess of lipid decreases insulin sensitivity or activity that causes insulin resistance, a stage which occupies the centre of pathogenesis in T2D. Lipid induces adipose tissue inflammation that accompanies certain critical defects in adipocytes, a major cell in abdominal adipose tissue. These include increased population of hypertrophied adipocytes, decline in adipokines secretion, attenuation of adipogenesis, and increased lipotoxicity effecting greater deposition of fat which interferes with glucose uptake by insulin target cells. Inflammation of adipose tissue is further intensified due to the infiltration of macrophages, a member of the innate immune system, and their transformation from anti-inflammatory M2 to proinflammatory M1 phenotype. Hence, secretion of proinflammatory cytokines from both M1 macrophage and inflamed adipocytes is greatly elevated which adversely causes insulin resistance that leads to T2D. Association between lipid-induced inflammation and insulin resistance makes diabetes a critical disease.