Abstract

BackgroundFunctional brown adipose tissue (BAT), involved in energy expenditure, has recently been detected in substantial amounts in adults. Formerly overlooked BAT has now become an attractive anti-obesity target.Methods and resultsMolecular characterization of human brown and white adipocytes, using a myriad of techniques including high-throughput RNA sequencing and functional assays, showed that PAZ6 and SW872 cells exhibit classical molecular and phenotypic markers of brown and white adipocytes, respectively. However, the pre-adipocyte cell line SGBS presents a versatile phenotype. A transit expression of classical brown markers such as UCP1 and PPARγ peaked and declined at day 28 post-differentiation initiation. Conversely, white adipocyte markers, including Tcf21, showed reciprocal behavior. Interestingly, leptin levels peaked at day 28 whereas the highest adiponectin mRNA levels were detected at day 14 of differentiation. Phenotypic analysis of the abundance and shape of lipid droplets were consistent with the molecular patterns. Accordingly, the oxidative capacity of SGBS adipocytes peaked on differentiation day 14 and declined progressively towards differentiation day 28.ConclusionsOur studies have unveiled a new phenotype of human adipocytes, providing a tool to identify molecular gene expression patterns and pathways involved in the conversion between white and brown adipocytes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0480-6) contains supplementary material, which is available to authorized users.

Highlights

  • Functional brown adipose tissue (BAT), involved in energy expenditure, has recently been detected in substantial amounts in adults

  • Our studies have unveiled a new phenotype of human adipocytes, providing a tool to identify molecular gene expression patterns and pathways involved in the conversion between white and brown adipocytes

  • Cold exposure of Simpson-Golabi-Behmel gigantism (SGBS) adipocytes activates BAT markers and leads to an enhanced brown adipocyte phenotype Lastly, we explored the capacity of SGBS cells to respond to cold cell-autonomously to see whether the brownish phenotype seen at D14 can be further enhanced

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Summary

Introduction

Functional brown adipose tissue (BAT), involved in energy expenditure, has recently been detected in substantial amounts in adults. Obesity most commonly results if the energy intake (e.g. through energy-dense food) exceeds energy expenditure, While some of the functions and implications of white adipose tissue (WAT) have been discovered and are investigated, understanding of the underlying biology is far from comprehensive or complete. In addition to WAT, functional BAT in adults has been discovered through radiological detection by several research groups [7,8,9] and has recently become a promising therapeutic target due to its ability to dissipate energy in form of heat, Guennoun et al Journal of Translational Medicine (2015) 13:135 through a process called non-shivering thermogenesis (or uncoupled respiration). Some studies propose that the amount of BAT in humans is inversely associated with BMI, i.e. healthy, normal-weight subjects bear a greater amount than obese or overweight individuals [11,12,13]

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