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Figure 3. Loss of CEACAM1 in hepatocytes causes insulin resistance and hepatic fibrosis. Loss of CEACAM1 in hepatocytes impairs insulin clearance, which causes hyperinsulinemia-driven hepatic insulin resistance and de novo lipogenesis (steatosis). Redistribution of VLDL-triglycerides to white adipose tissue causes visceral obesity and, eventually, excessive release of FA and adipokines, both of which could lead to systemic insulin resistance. In addition to fat accumulation in the liver, adipokines can alter the inflammatory milieu of the liver and steatohepatitis emerges. Both FA and IL-6 could transactivate EGFR in HSCs to mediate their activation and cause collagen production and hepatic fibrosis [Cf Figure 4]. CEACAM1: Carcinoembryonic antigen-related cell adhesion molecule 1; FA: fatty acids; EGFR: epidermal growth factor receptor; HSCs: hepatic stellate cells; IR: insulin receptor; FASN: fatty acid synthase.