title: Arginase inhibition ameliorates adipose tissue inflammation in mice with diet-induced obesity.
abstract: This study examined whether oral administration of an arginase inhibitor regulates adipose tissue macrophage infiltration and inflammation in mice with high fat diet (HFD)-induced obesity. Male C57BL/6 mice (n = 30) were randomly assigned to control (CTL, n = 10), HFD only (n = 10), and HFD with arginase inhibitor N(ω)-hydroxy-nor-l-arginine (HFD with nor-NOHA, n = 10) groups. Plasma and mRNA levels of cytokines in epididymal adipose tissues (EAT), macrophage infiltration into EAT, and macrophage phenotype polarization were measured in the animals after 12 weeks. Additionally, the effects of nor-NOHA on adipose tissue macrophage infiltration and mRNA expression of cytokines were measured in co-cultured 3T3-L1 adipocytes and RAW 264.7 macrophages. Macrophage infiltration into the adipocytes was significantly suppressed by nor-NOHA treatment in adipocyte/macrophage co-culture system and mice with HFD-induced obesity. Pro-inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), were significantly downregulated, and the anti-inflammatory cytokine IL-10 was significantly upregulated in nor-NOHA-treated co-cultured cells. In the mice with HFD-induced obesity, plasma and mRNA levels of MCP-1 significantly reduced after supplementation with nor-NOHA. In addition, oral supplement of nor-NOHA modified M1/M2 phenotype ratio in the EAT. Oral supplementation of an arginase inhibitor, nor-NOHA, altered M1/M2 macrophage phenotype and macrophage infiltration into HFD-induced obese adipose tissue, thereby improved adipose tissue inflammatory response. These results may indicate that arginase inhibition ameliorates obesity-induced adipose tissue inflammation.
authors.affiliation: Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Huan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Depament of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Applied Bioscience, CHA University, Gyeonggi-do 463-400, Republic of Korea.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Food Science and Nutrition, College of Health Science, Dong-A University, Busan 604-714, Republic of Korea.
authors.forename: Oh Yoen
authors.initials: OY
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul 136-701, Republic of Korea; Depament of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul 136-701, Republic of Korea; Korea University Guro Hospital, Korea University, Seoul 152-703, Republic of Korea. Electronic address: mjshin@korea.ac.kr.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Shin
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects; D000273:Adipose Tissue / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000188:drug therapy / Q000209:etiology; D015434:Panniculitis / Q000188:drug therapy* / Q000209:etiology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D004791:Enzyme Inhibitors; C404735:N(omega)-hydroxynorarginine; D001120:Arginine; D001119:Arginase
keywords: Adipocytes; Arginase; Inflammation; Macrophage infiltration; Nor-NOHA