Figure 3 Candidate signalling pathways of irisin in hepatocytes

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Figure 3 Candidate signalling pathways of irisin in hepatocytes Figure 3 | Candidate signalling pathways of irisin in hepatocytes. Irisin reduces gluconeogenesis by downregulating the expression of PCK1 (also known as PEPCKC) and G6PC via AMP-activated protein kinase (AMPK) and the phosphoinositide 3-kinase (PI3K)–AKT–FOXO1 signalling pathway. In addition, it stimulates glycogenesis via the PI3K–AKT–glycogen synthase kinase 3 (GSK3)–glycogen synthase (GS) pathway. Irisin inhibits palmitic acid-induced lipogenesis and lipid accumulation, as well as oxidative stress, by downregulating expression of PRMT3. This leads to reduced expression of several lipogenic markers (for example,liver x receptor-α (LXRα), sterol regulatory element-binding protein 1C (SREBP1C), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)) and inflammatory markers (such as the genes TNF and IL6, and the proteins cyclooxygenase 2 (COX2), nuclear factor-κB (NF-κB) andp38 mitogen-activated protein kinase (MAPK)). Perakakis, N. et al. (2017) Physiology and role of irisin in glucose homeostasis Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.221