title: RAGE regulates the metabolic and inflammatory response to high-fat feeding in mice.
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.
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY.
authors: Fei
authors: F
authors: Song
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY.
authors: Carmen
authors: C
authors: Hurtado del Pozo
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY.
authors: Rosa
authors: R
authors: Rosario
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY.
authors: Yu Shan
authors: YS
authors: Zou
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY.
authors: Radha
authors: R
authors: Ananthakrishnan
authors: Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, NY.
authors: Xiaoyuan
authors: X
authors: Xu
authors: Program in Molecular Medicine and Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
authors: Payal R
authors: PR
authors: Patel
authors: Program in Molecular Medicine and Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
authors: Vivian M
authors: VM
authors: Benoit
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY.
authors: Shi Fang
authors: SF
authors: Yan
authors: Departments of Population Health (Biostatistics) and Environmental Medicine, New York University School of Medicine, New York, NY.
authors: Huilin
authors: H
authors: Li
authors: Biomedical Informatics Shared Resource, Herbert Irving Comprehensive Cancer Center and Department of Biomedical Informatics, College of Physicians and Surgeons, Columbia University, New York, NY.
authors: Richard A
authors: RA
authors: Friedman
authors: Program in Molecular Medicine and Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
authors: Jason K
authors: JK
authors: Kim
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY.
authors: Ravichandran
authors: R
authors: Ramasamy
authors: Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, NY awf7@columbia.edu annmarie.schmidt@nyumc.org.
authors: Anthony W
authors: AW
authors: Ferrante
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY awf7@columbia.edu annmarie.schmidt@nyumc.org.
authors: Ann Marie
authors: AM
authors: Schmidt
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D015309:Glucose Clamp Technique; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015430:Weight Gain / Q000235:genetics
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic