Erythropoietin and long-acting erythropoiesis stimulating agent ameliorate non-alcoholic fatty liver disease by increasing lipolysis and decreasing lipogenesis via EPOR/STAT pathway
2019
Abstract Erythropoietin (EPO) has been reported to exert a beneficial effect on glucose metabolism in obesity. However, the effect of EPO on
lipid metabolismand non-alcoholic fatty liver disease (NAFLD) was unclear. Furthermore, the effect of long acting
erythropoiesis stimulating agents(ESA) on metabolism has not been poorly understood. The objective of this study was to investigate the effect of EPO and long acting ESA on NAFLD and
lipid metabolism. We administered EPO and darbepoetin alpha (DEPO), a long acting ESA, by intraperitoneally injection for 4 weeks to mice with high-fat-diet (HFD)-induced obesity. EPO and DEPO treatment reduced body weight, ameliorated glucose tolerance and insulin resistance, and prevented lipid accumulation in liver and
white adipose tissue(WAT). Administration of EPO and DEPO suppressed lipid synthesis-related protein in liver, including
sterol regulatory element-binding protein1 (SREBP-1),
acetyl-CoA carboxylase(ACC1) and
fatty acid synthase(FAS). EPO and DEPO also increased
lipolysisprotein in visceral WAT, including
hormone-sensitive lipase(HSL), atni-
adipose triglyceride lipase(ATGL). EPO and DEPO increased phosphorylation signal transducer and activator of transcription 3 (STAT3) and
STAT5, transcriptional factors with crucial roles of
lipid metabolism. These data suggest that EPO and DEPO ameliorated NAFLD by improving
lipid metabolismvia EPO/EPOR-induced STAT3 and
STAT5activation. EPO and DEPO may be a therapeutic option for NAFLD.
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