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Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism

The mitogen-activated protein kinases (MAPKs) participate in a multitude of processes that control hepatic metabolism. The liver regulates glucose and lipid metabolism, and under pathophysiological conditions such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NA...

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Published in:Trends in endocrinology and metabolism 2017-12, Vol.28 (12), p.868-878
Main Authors: Lawan, Ahmed, Bennett, Anton M.
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description The mitogen-activated protein kinases (MAPKs) participate in a multitude of processes that control hepatic metabolism. The liver regulates glucose and lipid metabolism, and under pathophysiological conditions such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) these processes become dysfunctional. Stress responses activate the hepatic MAPKs, and this is thought to impair insulin action and lipid metabolism. The MAPKs also activate the MAPK phosphatases (MKPs) which oppose their actions. How the MAPK/MKP balance is controlled in liver metabolism and how perturbations in these activities contribute to metabolic disease remains unclear. Discussion of recent insights into the MAPK/MKP signaling role in hepatic metabolic function and disease will be the focus of this review. In the liver, the concerted activities of the MAPKs result in the phosphorylation of downstream targets that regulate lipid metabolism and glucose homeostasis. Mouse models in which there is deficiency in the expression of the MAPKs (such as JNK, p38 MAPK, and the ERKs) reveal a variety of liver-related metabolic defects that result either directly or indirectly from the loss of these MAPKs. The balance of hepatic MAPK activity is crucial for normal liver function. Inactivation of MKPs, which oppose the MAPKs, also leads to altered hepatic lipid regulation and glucose production. Both altered activity and expression of the MAPKs and MKPs appear to occur in the livers of obesity models. How the balance between the MAPK and MKPs evokes a net signaling flux in the pathogenesis of insulin resistance and hepatic metabolic dysfunction remains unclear.
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subjects Animals
Diabetes Mellitus, Type 2 - enzymology
Diabetes Mellitus, Type 2 - metabolism
Humans
liver
Liver - metabolism
metabolism
mitogen-activated protein kinase
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Non-alcoholic Fatty Liver Disease - enzymology
Non-alcoholic Fatty Liver Disease - metabolism
obesity
signal transduction
Signal Transduction - genetics
Signal Transduction - physiology
type 2 diabetes
title Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism
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