title: The mAb against adipocyte fatty acid-binding protein 2E4 attenuates the inflammation in the mouse model of high-fat diet-induced obesity via toll-like receptor 4 pathway.
abstract: Adipocyte fatty acid-binding protein (A-FABP) plays an important role in fatty acid-mediated processes and related metabolic and inflammatory responses. In this study, we prepared a novel monoclonal antibody against A-FABP, designated 2E4. Our data showed that 2E4 specifically binded to the recombinant A-FABP and native A-FABP of mice adipose tissue. Furthermore, we investigated the effect of 2E4 on metabolic and inflammatory responses in C57BL/6J obese mice fed on a high fat diet. 2E4 administration improved glucose response in high-fat-diet induced obese mice. The 2E4 treated groups exhibited lower free fatty acids, cholesterol, and triglycerides in a concentration-dependent manner. These changes were accompanied by down-regulated expression of pro-inflammatory cytokines in adipose tissue, including tumor necrosis factor α, monocyte chemotactic protein-1, and interleukin-6. Meanwhile, our data demonstrated that 2E4 significantly decreased the mRNA and protein levels of A-FABP in adipose tissue of mice. Further experiments showed that 2E4 notably suppressed the phosphorylation of IκBα and jun-N-terminal kinase through toll-like receptor 4 signaling pathway. Taken together, 2E4 is an effective monoclonal antibody against A-FABP, which attenuated the inflammatory responses induced in the high-fat-diet mice. These findings may provide scientific insight into the treatment of chronic low-grade inflammation in obesity.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Miao
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lv
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China. Electronic address: minwang@cpu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China. Electronic address: yinhongping63@hotmail.com.
authors.forename: Hongping
authors.initials: H
authors.lastname: Yin
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D000072000:NF-KappaB Inhibitor alpha; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D000911:Antibodies, Monoclonal; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004041:Dietary Fats; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D020672:I-kappa B Proteins; D015850:Interleukin-6; C000606205:Nfkbia protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D002784:Cholesterol; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Adipocyte fatty acid binding protein; Inflammation; Monoclonal antibody 2E4; Toll-like receptor 4