Brown fat as a therapy for obesity and diabetes

Abstract

Purpose of review: Human fat consists of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. This review evaluates the recent discoveries regarding the identification of functional BAT in adult humans and its potential as a therapy for obesity and diabetes.

Recent findings: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry, and gene and protein expression assays to prove conclusively that adult humans have functional BAT. This has occurred against a backdrop of basic studies defining the origins of BAT, new components of its transcriptional regulation, and the role of hormones in stimulation of BAT growth and differentiation.

Summary: Adult humans have functional BAT, a new target for antiobesity and antidiabetes therapies focusing on increasing energy expenditure. Future studies will refine the methodologies used to measure BAT mass and activity, expand our knowledge of critical-control points in BAT regulation, and focus on testing pharmacological agents that increase BAT thermogenesis and help achieve long-lasting weight loss and an improved metabolic profile.

Figure 1. The presence and absence of detectable BAT via ¹⁸ F-FDG PECT/CT

Shown are the attenuation-corrected coronal and axial PET (left), CT (center), and fused PET/CT (right) images of a 60 year-old woman with substantial amounts of BAT. The intense yellow regions in the PET/CT images correspond to the cervical and supraclavicular BAT depots.

Figure 2. Therapies for obesity and diabetes that target the BAT differentiation and activation pathway

The development of a fully functional brown adipocyte can be divided into three phases: the multipotent mesenchymal stem cell; the brown preadipocyte; and the mature brown adipocytes. Shown in the upper part of the panel are key hormonal regulators of each phase. There are two principal approaches to utilizing BAT as a therapy for obesity and diabetes. One is the conventional in-vitro pharmaceutical approach of developing hormones or drugs that activate components of the pathway leading from the precursor cells to mature, activated brown adipocytes. The other is a novel ex-vivo strategy whereby progenitor cells are isolated from patients surgically, treated with factors that promote brown adipocyte differentiation, and then transplanted back into the same individuals to establish functional BAT that can be activated to burn off excess calories.