Development of hepatic insulin resistance during nonalcoholic steatohepatitis. Nonalcoholic steatohepatitis (NASH) pathogenesis and insulin resistance are based on the complex interplay between white fat tissue, hepatocytes and interfering inflammatory cells. A high-calorie diet induces metabolic and inflammatory stress in white fat tissue cells, which in turn releases free fatty acids in increasing amounts into the portal blood flow. In the liver, insulin resistance is then promoted through the release of proinflammatory cytokines provided by infiltrating inflammatory cells, which sustains the inflammatory response further. ER, endoplasmic reticulum; IL-6, interleukin 6; MCP-1, monocyte chemoattractant protein 1; NFκB, nuclear factor κB; SOCS3, suppressor of cytokine signalling 3; TNF-α, tumour necrosis factor α.