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

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

Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2016
Publication Date: 1/19/2016
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 [abstract]. Keystone Symposia. February 15-19, 2016, Banff, Alberta, Canada. Poster number 1051.

Interpretive Summary: Beige or brite (brown in white) adipocytes are cells that arise in white adipose tissue (WAT) in response to stimuli like excess energy, exercise, or cold exposure. The induction of beige adipocytes (beigeing) confers resistance to obesity and type-2 diabetes in animal models. There is a growing interest in exploiting beigeing to combat obesity and its comorbidities. However, there is some uncertainty regarding the best markers to evaluate beigeing in WAT. We evaluated the transcript expression of several murine thermoregulatory genes and proposed beige markers employing cell culture, whole inguinal WAT, and the adipocyte and stromal vascular fractions. 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 WAT of younger mice and 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 beigeing. The markers TMEM26 and CD137 were not increased in whole inguinal WAT or in the adipocyte fraction by cold exposure. We concluded that while most putative beige markers are clearly expressed in beige adipocytes in vitro, 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 in vivo, although this limitation may be overcome by specifically evaluating these markers in the adipocyte fraction. In contrast, thermoregulatory gene markers were consistently induced by all beigeing treatments thus representing one of the best beige adipocyte makers to use in vivo.

Technical Abstract: Beige or brite (brown in white) adipocytes are cells that arise in white adipose tissue (WAT) in response to stimuli like excess energy, exercise, or cold exposure. The induction of beige adipocytes (beigeing) confers resistance to obesity and type-2 diabetes in animal models. There is a growing interest in exploiting beigeing to combat obesity and its comorbidities. However, there is some uncertainty regarding the best markers to evaluate beigeing in WAT. We evaluated the transcript expression of several murine thermoregulatory genes and proposed beige markers employing cell culture, whole inguinal WAT, and the adipocyte and stromal vascular fractions. 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 WAT of younger mice and 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 beigeing. The markers TMEM26 and CD137 were not increased in whole inguinal WAT or in the adipocyte fraction by cold exposure. We concluded that while most putative beige markers are clearly expressed in beige adipocytes in vitro, 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 in vivo, although this limitation may be overcome by specifically evaluating these markers in the adipocyte fraction. In contrast, thermoregulatory gene markers were consistently induced by all beigeing treatments thus representing one of the best beige adipocyte makers to use in vivo.