Abstract

White and brown adipocytes are believed to occupy different sites in the body. We studied the anatomical features and quantitative histology of the fat depots in obesity and type 2 diabetes-prone C57BL/6J mice acclimated to warm or cold temperatures. Most of the fat tissue was contained in depots with discrete anatomical features, and most depots contained both white and brown adipocytes. Quantitative analysis showed that cold acclimation induced an increase in brown adipocytes and an almost equal reduction in white adipocytes; however, there were no significant differences in total adipocyte count or any signs of apoptosis or mitosis, in line with the hypothesis of the direct transformation of white into brown adipocytes. The brown adipocyte increase was accompanied by enhanced density of noradrenergic parenchymal nerve fibers, with a significant correlation between the density of these fibers and the number of brown adipocytes. Comparison with data from obesity-resistant Sv129 mice disclosed a significantly different brown adipocyte content in C57BL/6J mice, suggesting that this feature could underpin the propensity of the latter strain to develop obesity. However, the greater C57BL/6J browning capacity can hopefully be harnessed to curb obesity and type 2 diabetes in patients with constitutively low amounts of brown adipose tissue.

Highlights

  • White and brown adipocytes are believed to occupy different sites in the body

  • brown adipose tissue (BAT), which is generally considered as being composed of multilocular adipocytes immunoreactive for uncoupling protein1 (UCP1), its functional thermogenic protein, and white adipose tissue (WAT), a tissue widely believed to be composed of UCP1-negative unilocular adipocytes, are commonly held

  • Morphology and UCP1 staining demonstrated that most depots are composed of three specific types of adipocytes: UCP1-negative unilocular adipocytes, UCP1-positive multilocular adipocytes, and UCP1-negative multilocular adipocytes

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Summary

Introduction

White and brown adipocytes are believed to occupy different sites in the body. We studied the anatomical features and quantitative histology of the fat depots in obesity and type 2 diabetes-prone C57BL/6J mice acclimated to warm or cold temperatures. Previous work, mainly from our lab, supports the notion that WAT and BAT are found together in subcutaneous and visceral fat depots, collectively forming a multidepot organ that we have called the “adipose organ” [4, 5]. It has been suggested that the obesity and diabetes resistance of A/J mice may be due to a strong increase in brown adipocytes in some “classic” white adipose depots after cold exposure or treatment with a ␤3 adrenergic agonist [23, 24]. A previous work by our group showed that intermuscular fat in the hind legs of C57BL/6J mice contains fewer brown adipocytes than the intermuscular fat of obesity-resistant Sv129 mice (substrain 129/SVPAS SPF/VAF), suggesting the possibility that a difference in BAT amount could explain the susceptibility to obesity and type 2 diabetes of C57BL/6J

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