What is the clinical evidence from this study?

Study design: Other. Population: Beige adipogenesis. Intervention: Cold exposure vs. Room temperature (22 °C). Primary outcome: Transcript expression of thermoregulatory genes and beige markers.

March 18, 2016Nutrition & Metabolism127 citationsOpen Access

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

RGRolando A.G. GarciaAgricultural Research Service JRJames N. RoemmichAgricultural Research Service KCKate ClaycombeAgricultural Research Service

Key Result

Thermoregulatory markers like UCP1, CIDEA, and Cox8b represent the best options to evaluate the beigeing of white adipose tissue in vivo, as most putative beige markers have a small dynamic range.

Structured PICO

Population

Male C57BL/6 mice aged 2 to 4 months evaluated for beige adipocyte markers in white adipose tissue following cold exposure or in vitro differentiation.

Intervention

Cold exposure (5 °C for one week) for in vivo experiments; rosiglitazone (1 uM) and T3 (1 nM) for in vitro beige adipocyte differentiation.

Comparator

Room temperature (22 °C) for in vivo experiments; white adipocyte differentiation medium without rosiglitazone and T3 for in vitro experiments.

Outcome

Transcript expression of thermoregulatory genes (UCP1, CIDEA, Cox8b) and putative beige markers (FGF21, P2RX5, PAT2, CAR4, etc.) in white adipose tissue and cell cultures.surrogate

Thermoregulatory markers like UCP1, CIDEA, and Cox8b represent the best options to evaluate the beigeing of white adipose tissue in vivo, outperforming other putative beige markers.

Limitations

Species-dependent difference, age differences, and animal housing temperature may contribute to differences in beige adipocyte marker gene expression.
Results obtained from the application of beige markers validated in rodents to human samples should be interpreted with caution.
The low dynamic range of some markers, the age of the mice, and the strength of the beigeing stimulus may limit their utility in vivo.

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. 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.

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