We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dual CCR2/5 Antagonist Attenuates Obesity-Induced Insulin Resistance by Regulating Macrophage Recruitment and M1/M2 Status.
- Authors
Huh, Ji Hye; Kim, Hong Min; Lee, Eun Soo; Kwon, Mi Hye; Lee, Bo Ra; Ko, Hyun‐Jeong; Chung, Choon Hee; Ko, Hyun-Jeong
- Abstract
<bold>Objective: </bold>Adipose tissue inflammation induced by macrophage infiltration through the C-C motif chemokine receptor (CCR) 2 or CCR5 pathway has a pivotal role in obesity-related disease and insulin resistance. Here, the effect of PF4178903, a dual CCR2/CCR5 antagonist, on obesity and insulin resistance was evaluated.<bold>Methods: </bold>Forty male C57BL/6J mice were divided into four groups as follows: (1) regular diet (RD), (2) RD with PF4178903, (3) high-fat diet (HFD), and (4) HFD with PF4178903. All mice were sacrificed 12 weeks after the beginning of the experiment. Biochemical analyses and adipose tissue examinations were performed.<bold>Results: </bold>After treatment with PF4178903, both body weight and adipocyte size in white adipose tissue were decreased in HFD-fed mice. Furthermore, PF4178903 treatment reduced adipose tissue macrophages (ATMs) and lowered serum proinflammatory cytokines in HFD-fed mice. PF4178903 treatment significantly improved HFD-induced insulin resistance and glucose intolerance. Fluorescence-activated cell sorter analysis revealed that PF4178903 treatment reduced the CD8 + T cell fraction in white adipose tissue of HFD-fed mice. PF4178903 treatment reduced M1-polarized macrophages while inducing an M2-dominant shift in macrophages within white adipose tissue in HFD-fed mice.<bold>Conclusions: </bold>Dual CCR2/CCR5 antagonism ameliorates insulin resistance and inflammation in obesity by regulating ATM recruitment and polarization in white adipose tissue.
- Subjects
OBESITY treatment; INSULIN resistance; MACROPHAGES; LABORATORY mice; ADIPOSE tissues
- Publication
Obesity (19307381), 2018, Vol 26, Issue 2, p378
- ISSN
1930-7381
- Publication type
journal article
- DOI
10.1002/oby.22103