Nat. Rev. Endocrinol. doi: /nrendo

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Nat. Rev. Endocrinol. doi:10.1038/nrendo.2017.56 Figure 2 Liver steatosis, hepatokine secretion and metabolic dysregulation Figure 2 | Liver steatosis, hepatokine secretion and metabolic dysregulation. The hepatocyte protein secretome undergoes marked changes in response to liver steatosis. Increased intrahepatic levels of triglycerides induce changes in hepatokine transcription and endoplasmic reticulum (ER) processing, leading to the increased secretion of some hepatokines during steatosis (↑) and to the decreased secretion of other hepatokines (↓). Hepatokines are secreted and act in autocrine and paracrine manners to signal to hepatocytes, and function systemically through transport to distant target tissues, including the skeletal muscle, adipose tissue, blood vessels and pancreas. The metabolic effects of increased and decreased concentrations of specific hepatokines are reported. Collectively, these metabolic effects lead to the development of insulin resistance, glucose intolerance, ectopic lipid accumulation, inflammation and impaired insulin secretion. ANGPTL4, angiopoietin-like protein 4; LECT2, leukocyte cell-derived chemotaxin 2; RBP4, retinol-binding protein 4; SHBG, sex hormone-binding globulin. Meex, R. C. R. & Watt, M. J. (2017) Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance Nat. Rev. Endocrinol. doi:10.1038/nrendo.2017.56