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RAGE regulates the metabolic and inflammatory response to high-fat feeding in mice.
- Source :
-
Diabetes [Diabetes] 2014 Jun; Vol. 63 (6), pp. 1948-65. Date of Electronic Publication: 2014 Feb 11. - Publication Year :
- 2014
-
Abstract
- In mammals, changes in the metabolic state, including obesity, fasting, cold challenge, and high-fat diets (HFDs), activate complex immune responses. In many strains of rodents, HFDs induce a rapid systemic inflammatory response and lead to obesity. Little is known about the molecular signals required for HFD-induced phenotypes. We studied the function of the receptor for advanced glycation end products (RAGE) in the development of phenotypes associated with high-fat feeding in mice. RAGE is highly expressed on immune cells, including macrophages. We found that high-fat feeding induced expression of RAGE ligand HMGB1 and carboxymethyllysine-advanced glycation end product epitopes in liver and adipose tissue. Genetic deficiency of RAGE prevented the effects of HFD on energy expenditure, weight gain, adipose tissue inflammation, and insulin resistance. RAGE deficiency had no effect on genetic forms of obesity caused by impaired melanocortin signaling. Hematopoietic deficiency of RAGE or treatment with soluble RAGE partially protected against peripheral HFD-induced inflammation and weight gain. These findings demonstrate that high-fat feeding induces peripheral inflammation and weight gain in a RAGE-dependent manner, providing a foothold in the pathways that regulate diet-induced obesity and offering the potential for therapeutic intervention.<br /> (© 2014 by the American Diabetes Association.)
- Subjects :
- Animals
Glucose Clamp Technique
Inflammation genetics
Macrophages metabolism
Male
Mice
Mice, Inbred C57BL
Obesity genetics
Real-Time Polymerase Chain Reaction
Receptor for Advanced Glycation End Products
Weight Gain genetics
Adipose Tissue metabolism
Diet, High-Fat
Inflammation metabolism
Insulin Resistance genetics
Liver metabolism
Obesity metabolism
Receptors, Immunologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 63
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 24520121
- Full Text :
- https://doi.org/10.2337/db13-1636