Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice
-
Published:2012-02-07
Issue:1
Volume:11
Page:
-
ISSN:1476-511X
-
Container-title:Lipids in Health and Disease
-
language:en
-
Short-container-title:Lipids Health Dis
Author:
Altintas Mehmet M,Nayer Behzad,Walford Eric C,Johnson Kevin B,Gaidosh Gabriel,Reiser Jochen,De La Cruz-Munoz Nestor,Ortega Luis M,Nayer Ali
Abstract
Abstract
Background
Mast cells are implicated in the pathogenesis of obesity and insulin resistance. Here, we explored the effects of leptin deficiency-induced obesity on the density of mast cells in metabolic (abdominal fat depots, skeletal muscle, and liver) and lymphatic (abdominal lymph nodes, spleen, and thymus) organs. Fourteen-week-old male leptin-deficient ob/ob mice and their controls fed a standard chow were studied. Tissue sections were stained with toluidine blue to determine the density of mast cells. CD117/c-kit protein expression analysis was also carried out. Furthermore, mast cells containing immunoreactive tumor necrosis factor-α (TNF-α), a proinflammatory cytokine involved in obesity-linked insulin resistance, were identified by immunostaining.
Results
ob/ob mice demonstrated adiposity and insulin resistance. In abdominal fat depots, mast cells were distributed differentially. While most prevalent in subcutaneous fat in controls, mast cells were most abundant in epididymal fat in ob/ob mice. Leptin deficiency-induced obesity was accompanied by a 20-fold increase in the density of mast cells in epididymal fat, but a 13-fold decrease in subcutaneous fat. This finding was confirmed by CD117/c-kit protein expression analysis. Furthermore, we found that a subset of mast cells in epididymal and subcutaneous fat were immunoreactive for TNF-α. The proportion of mast cells immunoreactive for TNF-α was higher in epididymal than in subcutaneous fat in both ob/ob and control mice. Mast cells were also distributed differentially in retroperitoneal, mesenteric, and inguinal lymph nodes. In both ob/ob mice and lean controls, mast cells were more prevalent in retroperitoneal than in mesenteric and inguinal lymph nodes. Leptin deficiency-induced obesity was accompanied by increased mast cell density in all lymph node stations examined. No significant difference in the density of mast cells in skeletal muscle, liver, spleen, and thymus was noted between ob/ob and control mice.
Conclusions
This study demonstrates that leptin deficiency-induced obesity is accompanied by alterations in the density of mast cells in abdominal fat depots. The divergent distribution of mast cells in subcutaneous versus visceral fat might partially account for their differential biological behavior. Mast cells might also play a role in adaptive immune response occurring in regional lymph nodes in obesity.
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry, medical,Clinical Biochemistry,Endocrinology,Endocrinology, Diabetes and Metabolism
Reference33 articles.
1. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS: Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA. 2001, 289: 76-79. 2. Hotamisligil GS: Inflammation and metabolic disorders. Nature. 2006, 444: 860-867. 10.1038/nature05485 3. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS: Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005, 46: 2347-2355. 10.1194/jlr.M500294-JLR200 4. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H: Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003, 112: 1821-1830. 5. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D: Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009, 15: 930-939. 10.1038/nm.2002
Cited by
21 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|