Potential novel therapeutic strategies from understanding adipocyte transdifferentiation mechanisms

Abstract

Brown adipocytes are located in discrete anatomical locations in both small mammals and in humans. ‘Brown-like’ adipocytes, also known as brite (brown in white) or beige adipocytes are found interspersed among white adipocytes in several fat depots. From a functional point of view, the activity of brown and brite cells is similar, that is, heat production mediated by uncoupling protein 1. The morphology and expression of ‘thermogenic’ genes is also very similar in these two cell types. The origin of brite adipocytes is under intense investigation because enhancing their presence and activity has the potential to promote a healthy metabolic profile. Transdifferentiation mechanisms as well as de novo recruitment have been investigated. The characterization of the mechanisms involved in the recruitment and activation of brown/brite adipocytes in adult humans, could open the avenue for promising therapeutic strategies to curb metabolic diseases.

Keywords:

• BAT
• beige AT
• brite adipocytes
• brown adipocytes
• metabolic syndrome
• morphology
• plasticity
• transdifferentiation
• WAT
• white adipocytes

Acknowledgements

We apologize to those whose work was not directly cited because of space limitation.

Financial & competing interests disclosure

The authors were supported by EU FP7 project DIABAT (HEALTH-F2-2011-278373). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Fat in rodents and humans is distributed in multiple depots that together form the adipose organ.

• Some depots are mainly composed of white adipocytes, others are mainly composed of brown adipocytes, and some depots are beige AT and are composed of white, white-like (masked brite) and brown-like (brite) adipocytes.

• The activation of the thermogenic components of the organ (brown and brite adipocytes) helps to rebalance energy homeostasis in obese rodents and patients.

• Understanding the plasticity of adipocytes and possible transdifferentiation phenomena in the adipose organ could be of paramount importance in developing therapeutic strategies.

• Brown fat development and function are regulated by several hormonal factors derived from central and peripheral sources, such as the liver, skeletal muscle, and heart.

• Human brown adipocyte cell lines are needed to test and validate molecules identified as brown/brite adipocytes activators in mice.

• To translate basic research into clinical practice, alternative tools aside from FDG-PET/CT are needed for human brown adipocytes diagnosis.

Notes