Abstract
BackgroundThere is a growing interest in exploiting the induction of beige or “brite” (brown in white) adipocytes (beigeing) to combat obesity and its comorbidities. However, there is some uncertainty regarding the best markers to evaluate the occurrence or magnitude of beigeing in white adipose tissue in the mouse model.MethodsWe evaluated the transcript expression of several thermoregulatory genes and proposed beige markers employing cell culture, whole white adipose tissue, and the adipocyte and stromal vascular fractions.ResultsMost beige markers tested with the exception of TMEM26 can discriminate white from beige adipocytes in culture. Markers FGF21, P2RX5, PAT2, or CAR4 can successfully mark beigeing in whole tissue of younger mice, or in the adipocyte subfraction of older mice. However, markers for the thermoregulatory genes UCP1, CIDEA, and Cox8b displayed the greatest dynamic range and were consistently elevated in vitro, in vivo, and in the adipocyte fraction by treatments that induce beige adipogenesis.ConclusionsWhile most putative beige markers are clearly expressed in beige adipocytes in vitro, in vivo the small dynamic range of most of these markers, the strength of the beigeing stimulus, and the age of the mice may limit their utility, although this limitation may be overcome by specifically evaluating these markers in the adipocyte fraction. Thermoregulatory markers like UCP1, CIDEA, or Cox8b represent the best options to evaluate the beigeing of white adipose tissue in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0081-2) contains supplementary material, which is available to authorized users.
Highlights
There is a growing interest in exploiting the induction of beige or “brite” adipocytes to combat obesity and its comorbidities
Beige adipocyte marker gene expression differences after white and beige adipocyte differentiation Expression of the thermoregulatory genes Uncoupling Protein-1 (UCP1), Cell Death-Inducing DFFA-Like Effector A (CIDEA), and Cox8b was elevated 147, 178, and 4fold, respectively, in cells treated with rosiglitazone (Fig. 1a-c), and hereafter referred to as beige adipocytes
In this work we evaluated the expression of the transcripts for thermoregulatory genes and putative beige markers in cultured murine stromal vascular fraction (SVF) cells differentiated into white and beige adipocytes, and in whole subcutaneous white adipose tissue, and its two major fractions of mice exposed to cold temperature to induce beigeing
Summary
There is a growing interest in exploiting the induction of beige or “brite” (brown in white) adipocytes (beigeing) to combat obesity and its comorbidities. Beige or “brite” (brown in white) adipocytes arise in white adipose tissue (WAT) in response to various stimuli including cold exposure and exercise. When the amount of brown adipose tissue is greatly reduced in mice by genetic means, the induction of beige adipocytes in white adipose tissue can restore the thermogenic response to cold and prevent the mice from becoming more susceptible to weight gain in response to a high-fat diet [4]. Mice lacking functional beige adipocytes are more prone to developing obesity, insulin resistance, and hepatic steatosis when fed a high-fat diet [5]. Transplantation of subcutaneous adipose tissue where beiging was induced by exercise into mice fed a high-fat diet restored glucose tolerance and insulin sensitivity [6].
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