Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Jun 8

PMID 28591572

Citations 77

Authors

Kasper W Ter Horst

Pim W Gilijamse

Ruth I Versteeg

Mariette T Ackermans

Aart J Nederveen

Susanne E la Fleur

Johannes A Romijn

Max Nieuwdorp

Dongyan Zhang

Varman T Samuel

Daniel F Vatner

Kitt F Petersen

Gerald I Shulman

Mireille J Serlie

Affiliations

Soon will be listed here.

Abstract

Hepatic lipid accumulation has been implicated in the development of insulin resistance, but translational evidence in humans is limited. We investigated the relationship between liver fat and tissue-specific insulin sensitivity in 133 obese subjects. Although the presence of hepatic steatosis in obese subjects was associated with hepatic, adipose tissue, and peripheral insulin resistance, we found that intrahepatic triglycerides were not strictly sufficient or essential for hepatic insulin resistance. Thus, to examine the molecular mechanisms that link hepatic steatosis to hepatic insulin resistance, we comprehensively analyzed liver biopsies from a subset of 29 subjects. Here, hepatic cytosolic diacylglycerol content, but not hepatic ceramide content, was increased in subjects with hepatic insulin resistance. Moreover, cytosolic diacylglycerols were strongly associated with hepatic PKCε activation, as reflected by PKCε translocation to the plasma membrane. These results demonstrate the relevance of hepatic diacylglycerol-induced PKCε activation in the pathogenesis of NAFLD-associated hepatic insulin resistance in humans.

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