Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice

Abstract

This article is available online at http://www.jlr.org is of grave consequence to human health. In fact, cardiovascular diseases, mostly as a result of long-standing metabolic dysregulations, are the leading cause of morbidity and mortality in many parts of the world.The pathogenesis of obesity-linked insulin resistance is only partially understood. Accumulating evidence has revealed a strong association between obesity-linked insulin resistance and infl ammation ( 2 ). Tumor necrosis factor-a (TNF-a ), a prototypical pro-infl ammatory cytokine, was upregulated in the epididymal fat of obese rodents, and neutralization of TNF-a ameliorated insulin resistance ( 3 ). Moreover, obese mice lacking TNF-a demonstrated improved insulin sensitivity ( 4 ). In addition, increased numbers of macrophages and their transcripts were reported in the epididymal fat of genetically and dietinduced obese (DIO) mice ( 5, 6 ). These adipose tissue macrophages (ATM) were found scattered between adipocytes (herein referred to as solitary ATM ) or forming clusters around adipocytes. Based on ultrastructural and immunohistochemical alterations, it was argued that most ATM in obese mice and humans surround dead adipocytes, forming so-called crown-like structures (CLS) ( 7 ). Subsequently, we reported that CLS were distributed differentially in abdominal fat depots of DIO mice ( 8 ). Consistent with our fi ndings, it was recently reported that CLS were also more prevalent in visceral than subcutaneous fat of leptin-defi cient ob/ob and leptin receptor-defi cient db/db mice ( 9 ).Although macrophages are critical in innate and adaptive immunity, most immune responses are the result of interplay between multiple cell types and mediators of the immune system ( 10 ). Therefore, it comes as no surprise to learn that regulatory T cells ( 11 ), CD8+ effector T cells Over the past several decades a steady increase in the prevalence of obesity across the continents, especially in the US, has been observed ( 1 ). Increased caloric intake, mostly due to consumption of a high-fat diet, and decreased physical activity seem to be major contributors. Insulin resistance, hypertension, and dyslipidemia often accompany obesity. The constellation, referred to as metabolic syndrome, This work was supported by generous funds from the Katz Family Foundation.

Cidea improves the metabolic profile through expansion of adipose tissue

“…3b,c). Thus, the increase in protein density in eWAT of wild-type mice could potentially be explained by a massive macrophage infiltration 13,[18][19][20][21] . Obesity-induced macrophage infiltration into eWAT seemed to be lower in transgenic than in wild-type mice (Fig.…”

“…However, prolonged exposure to high-fat diet invokes hypertrophy-associated death of epididymal adipocytes 13 and shrinkage of the entire eWAT (Fig. 8, top-right mouse); the tissue is invaded with macrophages that both clean up dead adipocytes and release proinflammatory cytokines 13,20,21 . Consequently, the remaining adipocytes are severely damaged (as demonstrated by the absence of perilipin 1), are non-functional (incompetent to produce adiponectin) and insulin-resistant (Akt deficient), which contributes to the development of systemic insulin resistance and poor health.…”

Is Serum Tryptase a Valuable Marker for Obesity-Bronchial Asthma Interrelationship in Children?

“…The increase in mast cells in visceral fat of obese mice [15] and in human subcutaneous abdominal fat [2], suggests their role in the pathogenesis of obesity and insulin resistance and infl ammatory status [2,15]. Similarly ,in an adult prospective study examining the effect of fat distribution on asthma found that abdominal obesity was a risk factor for incident asthma in males and females.…”

“…Furthermore, asthma has a higher prevalence in overweight and obese [14]. Obesity is accompanied by adipocyte death and accumulation of macrophages and mast cells in expanding adipose tissues [15]. Tryptases are serine peptidases highly abundant in granules of human and animal mast cells [16].…”

Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages

“…Epididymal adipose tissue (EAT) has been reported to be the most commonly used visceral fat depot in mouse studies, and its macrophage infiltration is most severe during the development of DIO [9]. In the lean state, EAT macrophages are mainly alternatively activated (M2) macrophages, which are characterised by CD206 and arginase 1.…”