Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates gluconeogenesis via activation of AMPK

International Journal of Obesity : Journal of the International Association for the Study of Obesity
Y-H LeeB-S Cha

Abstract

Activation of Notch signaling pathologically enhances lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that can modulate adipogenesis and muscle development in mice, was found as an inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic effect of exogenous DLK1 in vitro and in vivo. A soluble DLK1 peptide was generated with fusion between a human Fc fragment and extracellular domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle treated and DLK1-treated group (25 mg kg(-1), intraperitoneal injection, twice a week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in vitro experiments. After 4 weeks of DLK1 administration, hepatic triglyceride content and lipid droplets in liver tissues, as well as serum levels of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower levels of fasting and random g...Continue Reading

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Citations

Feb 8, 2018·The Journal of Biological Chemistry·Tae Woo JungJi Hoon Jeong
Aug 30, 2017·Nature Reviews. Endocrinology·Hitoshi Shimano, Ryuichiro Sato
Jan 17, 2019·Stem Cell Research & Therapy·Jiefang HuangHuanbai Xu
Aug 29, 2019·Archives of Endocrinology and Metabolism·Ana Pinheiro Machado CantonAna Claudia Latronico
Dec 17, 2020·Frontiers in Endocrinology·Guan WangGuangming Xiang
Sep 17, 2021·Frontiers in Cell and Developmental Biology·Congcong CaoShuiqiao Yuan

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