Loss-of-function Mutation in Toll-like Receptor 4 Prevents Diet-induced Obesity and Insulin Resistance.
From: Department of Internal Medicine, State University of Campinas, Campinas, São Paulo, Brazil.
Diabetes
- Publish Date: Aug 2007
- ISSN: 1939-327X
- Volume: 56
- Issue: 8
- Pages: 1986-98
- Medium: Internet
- Language: English
- Citation (JAMA): Tsukumo Daniela M L, Carvalho-Filho Marco A, Carvalheira José B C, et al. Loss-of-function Mutation in Toll-like Receptor 4 Prevents Diet-induced Obesity and Insulin Resistance.. Diabetes Aug 2007;56:1986-98
Abstract
Obesity is associated with insulin resistance and a state of abnormal inflammatory response. The Toll-like receptor (TLR)4 has an important role in inflammation and immunity, and its expression has been reported in most tissues of the body, including the insulin-sensitive ones. Because it is activated by lipopolysaccharide and saturated fatty acids, which are inducers of insulin resistance, TLR4 may be a candidate for participation in the cross-talk between inflammatory and metabolic signals. Here, we show that C3H/HeJ mice, which have a loss-of-function mutation in TLR4, are protected against the development of diet-induced obesity. In addition, these mice demonstrate decreased adiposity, increased oxygen consumption, a decreased respiratory exchange ratio, improved insulin sensitivity, and enhanced insulin-signaling capacity in adipose tissue, muscle, and liver compared with control mice during high-fat feeding. Moreover, in these tissues, control mice fed a high-fat diet show an increase in IkappaB kinase complex and c-Jun NH(2)-terminal kinase activity, which is prevented in C3H/HeJ mice. In isolated muscles from C3H/HeJ mice, protection from saturated fatty acid-induced insulin resistance is observed. Thus, TLR4 appears to be an important mediator of obesity and insulin resistance and a potential target for the therapy of these highly prevalent medical conditions.
Mesh Headings (Keywords): Adipose Tissue, Animal Feed, Animals, Blood Glucose, Body Weight, Cell Shape, Dietary Fats, Enzyme Activation, Fatty Acids, I-kappa B Kinase, Insulin, Insulin Resistance, JNK Mitogen-Activated Protein Kinases, Liver, Male, Mice, Microscopy, Electron, Transmission, Muscles, Mutation, Obesity, Phosphoproteins, Phosphoserine, Signal Transduction, Toll-Like Receptor 4, Triglycerides
Check for Full Text / PubMed Unique Identifier (PMID): 17519423
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