Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1842, Issue 11, Pages 2329-2343Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2014.08.004
Keywords
Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Insulin resistance; Inflammation; Kupffer cell; Lipid
Funding
- Dutch Heart Foundation [01C-104]
- Dutch Kidney Foundation [01C-104]
- Dutch Diabetes Research Foundation [2009.80.016, 2004.00.018]
- Dutch Center for Translational Molecular Medicine, project PREDICCt [01C-104]
Ask authors/readers for more resources
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. (C) 2014 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available