Evaluation of markers of beige adipocytes in white adipose tissue of the mouse

Authors: Garcia Garcia, Rolando; Roemmich, James; Larson, Kate

Submitted to: Nutrition and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/6/2016
Publication Date: 3/18/2016
Publication URL: http://handle.nal.usda.gov/10113/62645
Citation: Garcia Garcia, R.A., Roemmich, J.N., Claycombe, K.J. 2016. Evaluation of markers of beige adipocytes in white adipose tissue of the mouse. Nutrition and Metabolism. 13:24-36.

Interpretive Summary: Beige adipocytes are cells that arise in white adipose tissue in response to various environmental stimuli such as cold exposure and exercise. The primary beneficial role of beige adipocytes involves metabolizing cellular fat, especially during excess incoming energy. As a result, beige cells play an important role in reducing body fat and the development of obesity. Recent studies have suggested that these cells may play a key role in regulating metabolism, and there is interest in exploiting their potential to maintain a healthy body weight and counter obesity-related diseases. However, there is uncertainty as to which are the best markers to identify if a cell is a beige cell. In this study, we used mice to obtain cultured adipocytes, whole adipose tissue, and fractions isolated from the tissue to evaluate several markers of beigeing. We identified the best approaches to use beige adipocyte markers and to identify beige adipocytes. We also provide information regarding limitations that are associated with their use.

Technical Abstract: Background: There 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. Methods: We 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. Results: Most 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. The proposed beige markers TMEM26 and CD137 were found not to be markers of beige adipocytes in vivo. Conclusions: While 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. If feasible, measurement of markers like FGF21 or P2RX5 may yield additional information on the beigeing process.