TY - JOUR
T1 - Nonalcoholic fatty liver disease
T2 - A main driver of insulin resistance or a dangerous liaison?
AU - Gruben, Nanda
AU - Shiri-Sverdlov, Ronit
AU - Koonen, Debby P. Y.
AU - Hofker, Marten H.
N1 - Copyright © 2014 Elsevier B.V. All rights reserved.
PY - 2014/11
Y1 - 2014/11
N2 - Insulin resistance is one of the key components of the metabolic syndrome and it eventually leads to the development of type 2 diabetes, making it one of the biggest medical problems of modern society. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are tightly associated with insulin resistance. While it is fairly clear that insulin resistance causes hepatic steatosis, it is not known if NAFLD causes insulin resistance. Hepatic inflammation and lipid accumulation are believed to be the main drivers of hepatic insulin resistance in NAFLD. Here we give an overview of the evidence linking hepatic lipid accumulation to the development of insulin resistance, including the accumulation of triacylglycerol and lipid metabolites, such as diacylglycerol and ceramides. In particular, we discuss the role of obesity in this relation by reviewing the current evidence in terms of the reported changes in body weight and/or adipose tissue mass. We further discuss whether the activation or inhibition of inflammatory pathways, Kupffer cells and other immune cells influences the development of insulin resistance. We show that, in contrast to what is commonly believed, neither hepatic steatosis nor hepatic inflammation is sufficient to cause insulin resistance. Many studies show that obesity cannot be ignored as an underlying factor in this relationship and NAFLD is therefore less likely to be one of the main drivers of insulin resistance.
AB - Insulin resistance is one of the key components of the metabolic syndrome and it eventually leads to the development of type 2 diabetes, making it one of the biggest medical problems of modern society. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are tightly associated with insulin resistance. While it is fairly clear that insulin resistance causes hepatic steatosis, it is not known if NAFLD causes insulin resistance. Hepatic inflammation and lipid accumulation are believed to be the main drivers of hepatic insulin resistance in NAFLD. Here we give an overview of the evidence linking hepatic lipid accumulation to the development of insulin resistance, including the accumulation of triacylglycerol and lipid metabolites, such as diacylglycerol and ceramides. In particular, we discuss the role of obesity in this relation by reviewing the current evidence in terms of the reported changes in body weight and/or adipose tissue mass. We further discuss whether the activation or inhibition of inflammatory pathways, Kupffer cells and other immune cells influences the development of insulin resistance. We show that, in contrast to what is commonly believed, neither hepatic steatosis nor hepatic inflammation is sufficient to cause insulin resistance. Many studies show that obesity cannot be ignored as an underlying factor in this relationship and NAFLD is therefore less likely to be one of the main drivers of insulin resistance.
KW - Nonalcoholic fatty liver disease
KW - Nonalcoholic steatohepatitis
KW - Insulin resistance
KW - Inflammation
KW - Kupffer cell
KW - Lipid
KW - NF-KAPPA-B
KW - INDUCED HEPATIC STEATOSIS
KW - KUPFFER CELL ACTIVATION
KW - DIET-INDUCED OBESITY
KW - KINASE-C-EPSILON
KW - RECEPTOR SUBSTRATE-1
KW - SELECTIVE INSULIN
KW - OB/OB MICE
KW - DIACYLGLYCEROL ACYLTRANSFERASE
KW - SERINE PHOSPHORYLATION
U2 - 10.1016/j.bbadis.2014.08.004
DO - 10.1016/j.bbadis.2014.08.004
M3 - Review article
C2 - 25128743
SN - 0925-4439
VL - 1842
SP - 2329
EP - 2343
JO - Biochimica et biophysica acta-Molecular basis of disease
JF - Biochimica et biophysica acta-Molecular basis of disease
IS - 11
ER -