Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice

Abstract

Accumulation of visceral fat is a key phenomenon in the onset of obesity-associated metabolic disorders. Macrophage infiltration induces chronic mild inflammation widely considered as a causative factor for insulin resistance and eventually diabetes. We previously showed that .90% of macrophages infiltrating the adipose tissue of obese animals and humans are arranged around dead adipocytes, forming characteristic crown-like structures (CLS). In this study we quantified CLS in visceral and subcutaneous depots from two strains of genetically obese mice, db/db and ob/ob. In both strains, CLS were prevalent in visceral compared with subcutaneous fat. Adipocyte size and CLS density exhibited a positive correlation both in visceral and in subcutaneous depots; however, the finding that adipocyte size was smallest and CLS density highest in visceral fat suggests a different susceptibility of visceral and subcutaneous adipocytes to death. Visceral fat CLS density was 3.4-fold greater in db/db than in ob/ob animals, which at the age at which our experimental strain was used are more prone to glucose metabolic disorders.

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

“…These animals exhibited the same CLS density as obese animals (73). Notably, we found a positive correlation between CLS density and adipocyte size both in subcutaneous and visceral fat depots; their density was lower in subcutaneous fat containing larger adipocytes (79). Collectively, these data suggest that visceral adipocytes have a smaller death critical size (size-triggering death) (41), in line with the well-known greater morbidity due to accumulation of visceral fat (80).…”

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.…”

Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis

“…The number of F4/80-positive cells was counted in more than 10 mm 2 area of each section and expressed as the mean number per mm 2 . The CLS density was obtained by counting the total numbers of CLS and adipocytes in each section, which was expressed as CLS number per 10,000 adipocytes 41 . Antibodies used in this study for immunohistochemistry are listed in Supplementary Table 2.…”