The C-C motif chemokine receptor–2 (CCR2) regulates monocyte and macrophage recruitment and is necessary for macrophage-dependent inflammatory responses and the development of atherosclerosis. Although adipose tissue expression and circulating concentrations of CCL2 (also known as MCP1), a high-affinity ligand for CCR2, are elevated in obesity, the role of CCR2 in metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation associated with obesity, has not been studied. To determine what role CCR2 plays in the development of metabolic phenotypes, we studied the effects of Ccr2 genotype on the development of obesity and its associated phenotypes. Genetic deficiency in Ccr2 reduced food intake and attenuated the development of obesity in mice fed a high-fat diet. In obese mice matched for adiposity, Ccr2 deficiency reduced macrophage content and the inflammatory profile of adipose tissue, increased adiponectin expression, ameliorated hepatic steatosis, and improved systemic glucose homeostasis and insulin sensitivity. In mice with established obesity, short-term treatment with a pharmacological antagonist of CCR2 lowered macrophage content of adipose tissue and improved insulin sensitivity without significantly altering body mass or improving hepatic steatosis. These data suggest that CCR2 influences the development of obesity and associated adipose tissue inflammation and systemic insulin resistance and plays a role in the maintenance of adipose tissue macrophages and insulin resistance once obesity and its metabolic consequences are established.
Stuart P. Weisberg, Deborah Hunter, Reid Huber, Jacob Lemieux, Sarah Slaymaker, Kris Vaddi, Israel Charo, Rudolph L. Leibel, Anthony W. Ferrante Jr.
Title and authors | Publication | Year |
---|---|---|
Inflammation in obesity, diabetes, and related disorders
T Rohm, D Meier, J Olefsky, M Donath |
Immunity | 2022 |
Adipose tissue microenvironments during aging: Effects on stimulated lipolysis
C Camell |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2022 |
Insulin Resistance: From Mechanisms to Therapeutic Strategies
S Lee, S Park, C Choi |
Diabetes & Metabolism Journal | 2022 |
Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue
I AlZaim, A Al-Saidi, S Hammoud, N Darwiche, Y Al-Dhaheri, A Eid, A El-Yazbi |
Cancers | 2022 |
Impaired phosphocreatine metabolism in white adipocytes promotes inflammation
S Maqdasy, S Lecoutre, G Renzi, S Frendo-Cumbo, D Rizo-Roca, T Moritz, M Juvany, O Hodek, H Gao, M Couchet, M Witting, A Kerr, M Bergo, R Choudhury, M Aouadi, J Zierath, A Krook, N Mejhert, M Rydén |
Nature metabolism | 2022 |
Molecular mechanism of crosstalk between immune and metabolic systems in metabolic syndrome
R Hachiya, M Tanaka, M Itoh, T Suganami |
Inflammation and Regeneration | 2022 |
Intestinal microbe-dependent ω3 lipid metabolite αKetoA prevents inflammatory diseases in mice and cynomolgus macaques
T Nagatake, S Kishino, E Urano, H Murakami, N Kitamura, K Konishi, H Ohno, P Tiwari, S Morimoto, E Node, J Adachi, Y Abe, J Isoyama, K Sawane, T Honda, A Inoue, A Uwamizu, T Matsuzaka, Y Miyamoto, S Hirata, A Saika, Y Shibata, K Hosomi, A Matsunaga, H Shimano, M Arita, J Aoki, M Oka, A Matsutani, T Tomonaga, K Kabashima, M Miyachi, Y Yasutomi, J Ogawa, J Kunisawa |
Mucosal Immunology | 2022 |
The Complex Biology of the Obesity-Induced, Metastasis-Promoting Tumor Microenvironment in Breast Cancer
N Mubtasim, N Moustaid-Moussa, L Gollahon |
International journal of molecular sciences | 2022 |
Clinical monitored in subjects metabolically healthy and unhealthy before and during a SARS-CoV-2 infection– A cross-sectional study in Mexican population
S Treviño, S Cortezano-Esteban, H Hernández-Fragoso, A Díaz, R Vázquez-Roque, V Sarmiento-Ortega, D Moroni-González, R Pelayo, E Brambila |
Cytokine | 2022 |
Obesity, Adipose Tissue, and Inflammation Answered in Questions
V Guerreiro, D Carvalho, P Freitas, N Velotti |
Journal of Obesity | 2022 |
The Influence of Obesity and Weight Loss on the Bioregulation of Innate/Inflammatory Responses: Macrophages and Immunometabolism.
Gálvez I, Navarro MC, Martín-Cordero L, Otero E, Hinchado MD, Ortega E |
Nutrients | 2022 |
Subtype-Specific Surface Proteins on Adipose Tissue Macrophages and Their Association to Obesity-Induced Insulin Resistance
Strand K, Stiglund N, Haugstøyl ME, Kamyab Z, Langhelle V, Lawrence-Archer L, Busch C, Cornillet M, Hjellestad ID, Nielsen HJ, Njølstad PR, Mellgren G, Björkström NK, Fernø J |
Frontiers in Endocrinology | 2022 |
Role of adipose tissue macrophages in obesity-related disorders
Chakarov S, Blériot C, Ginhoux F |
Journal of Experimental Medicine | 2022 |
The Roles of Adipose Tissue Macrophages in Human Disease
Liang W, Qi Y, Yi H, Mao C, Meng Q, Wang H, Zheng C |
Frontiers in immunology | 2022 |
Monocyte Trafficking and Polarization Contribute to Sex Differences in Meta-Inflammation.
Varghese M, Clemente J, Lerner A, Abrishami S, Islam M, Subbaiah P, Singer K |
Frontiers in Endocrinology | 2022 |
Adipocyte-derived serum amyloid A promotes angiotensin II-induced abdominal aortic aneurysms in obese C57BL/6J mice
Shridas P, Ji A, Trumbauer AC, Noffsinger VP, Leung SW, Dugan AJ, Thatcher SE, Cassis LA, De Beer FC, Webb NR, Tannock LR |
Arteriosclerosis, thrombosis, and vascular biology | 2022 |
Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries
Fan Z, Zhang X, Shang Y, Zou M, Zhou M, E Q, Fei S, Chen W, Li J, Zhang X, Liu X |
International journal of molecular sciences | 2022 |
Adipocyte-Specific Ablation of PU.1 Promotes Energy Expenditure and Ameliorates Metabolic Syndrome in Aging Mice
Chen KY, De Angulo A, Guo X, More A, Ochsner SA, Lopez E, Saul D, Pang W, Sun Y, McKenna NJ, Tong Q |
2022 | |
Quantifying the inflammatory secretome of human intermuscular adipose tissue
Kahn D, Macias E, Zarini S, Garfield A, Zemski Berry K, Gerszten R, Schoen J, Cree\u2010Green M, Bergman BC |
Physiological Reports | 2022 |
Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution
Pomar CA, Bonet ML, Ferre-Beltrán A, Fraile-Ribot PA, García-Gasalla M, Riera M, Picó C, Palou A |
Biomedicines | 2022 |
Analytical performance of a canine ELISA monocyte chemoattractant protein-1 assay for use in cats and evaluation of circulating levels in normal weight and obese cats
Stenberg K, Gensby L, Cremer SE, Nielsen MM, Bjørnvad CR |
Acta veterinaria Scandinavica | 2022 |
Shared pathobiology identifies AMPK as a therapeutic target for obesity and autosomal dominant polycystic kidney disease.
Iliuta IA, Song X, Pickel L, Haghighi A, Retnakaran R, Scholey J, Sung HK, Steinberg GR, Pei Y |
Frontiers in Molecular Biosciences | 2022 |
Ameliorative effects of high intensity interval training and Lactobacillus rhamnosus GG Protect against tetracycline-induced fatty liver in rats: a gene expression profiling comparative study.
Hosseini HM, Shirvani H, Aghaei F, Arabzadeh E, Hofmeister M |
EXCLI journal | 2022 |
Bone marrow adipocytes drive the development of tissue invasive Ly6Chigh monocytes during obesity
Boroumand P, Prescott DC, Mukherjee T, Bilan PJ, Wong M, Shen J, Tattoli I, Zhou Y, Li A, Sivasubramaniyam T, Shi N, Zhu LY, Liu Z, Robbins C, Philpott DJ, Girardin SE, Klip A |
eLife | 2022 |
Immune and inflammatory mechanisms of abdominal aortic aneurysm
Márquez-Sánchez AC, Koltsova EK |
Frontiers in immunology | 2022 |
Role of the chemokine system in liver fibrosis: a narrative review
Poulsen KL, Cajigas-Du Ross CK, Chaney JK, Nagy LE |
2022 | |
Pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver disease.
Garbuzenko DV |
Gastroenterology and hepatology from bed to bench | 2022 |
The Effect of Healthy Lifestyle Strategies on the Management of Insulin Resistance in Children and Adolescents with Obesity: A Narrative Review
Calcaterra V, Verduci E, Vandoni M, Rossi V, Fiore G, Massini G, Berardo C, Gatti A, Baldassarre P, Bianchi A, Cordaro E, Cavallo C, Cereda C, Bosetti A, Zuccotti G |
Nutrients | 2022 |
Advances in T Cells Based on Inflammation in Metabolic Diseases
Yu W, Li C, Zhang D, Li Z, Xia P, Liu X, Cai X, Yang P, Ling J, Zhang J, Zhang M, Yu P |
Cells | 2022 |
Adipose tissue macrophages: Regulators of adipose tissue immunometabolism during obesity
Nance SA, Muir L, Lumeng C |
Molecular Metabolism | 2022 |
Time-restricted feeding reduces monocyte production by controlling hematopoietic stem and progenitor cells in the bone marrow during obesity
Kim Y, Lee Y, Lee MN, Nah J, Yun N, Wu D, Pae M |
Frontiers in immunology | 2022 |
Double life: How GRK2 and β-arrestin signaling participate in diseases
Zhai R, Snyder J, Montgomery S, Sato PY |
Cellular Signalling | 2022 |
Acetylation of PPARγ in macrophages promotes visceral fat degeneration in obesity
Aaron N, Zahr T, He Y, Yu L, Mayfield B, Pajvani UB, Qiang L |
2022 | |
Adipose tissue plasticity in health and disease
Sakers A, De Siqueira MK, Seale P, Villanueva CJ |
Cell | 2022 |