Signal Transduction Mechanisms of Alcoholic Fatty Liver Disease: Emer ging Role of Lipin-1.

Signal Transduction Mechanisms of Alcoholic Fatty Liver Disease: Emer ging Role of Lipin-1.

You Min; Jogasuria Alvin; Lee Kwangwon; Wu Jiashin; Zhang Yanqiao; Lee Yoon-Kwang; Sadana Prabodh

Current molecular pharmacology

2017

1905-7

Lipin-1, a mammalian phosphatidic acid phosphatase (PAP), is a bi-functional molecule involved in various signaling pathways via its function as a PAP enzyme in the triglyceride synthesis pathway and in the nucleus as a transcriptional co-regulator. In the liver, lipin-1 is known to play a vital role in controlling the lipid metabolism and inflammation process at multiple regulatory levels. Alcoholic fatty liver disease (AFLD) is one of the earliest forms of liver injury and approximately 8-20% of patients with simple steatosis can develop into more severe forms of liver injury, including steatohepatitis, fibrosis/ cirrhosis, and eventually hepatocellular carcinoma (HCC). The signal transduction mechanisms for alcohol-induced detrimental effects in liver involves alteration of complex and multiple signaling pathways largely governed by a central and upstream signaling system, namely, sirtuin 1 (SIRT1)-AMP activated kinase (AMPK) axis. Emerging evidence suggests a pivotal role of lipin-1 as a crucial downstream regulator of

Humans; Animals; AMP-Activated Protein Kinases/metabolism; Signal Transduction; Lipid Metabolism; Fatty Liver; Liver/metabolism; lipid metabolism; alcoholic fatty liver disease; inflammation; Lipin-1; signal transduction; transcriptional regulators; Phosphatidate Phosphatase/*metabolism; Inflammation/metabolism; Ethanol/chemistry/*metabolism; Sirtuin 1/metabolism; Alcoholic/*metabolism/pathology

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226–236

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