Adaptive thermogenesis in adipocytes: is beige the new brown?

Abstract

One of the most promising areas in the therapeutics for metabolic diseases centers around activation of the pathways of energy expenditure. Brown adipose tissue is a particularly appealing target for increasing energy expenditure, given its amazing capacity to transform chemical energy into heat. In addition to classical brown adipose tissue, the last few years have seen great advances in our understanding of inducible thermogenic adipose tissue, also referred to as beige fat. A deeper understanding of the molecular processes involved in the development and function of these cell types may lead to new therapeutics for obesity, diabetes, and other metabolic diseases.

Figure 1.

Origins of fat cells. At least three types of precursors give rise to white, beige, and brown adipose cells separately. Precursors for brown adipocytes developmentally originate from dermomyotome and express Pax7 and Myf5. White and beige adipocytes come from two distinct populations of precursors of Pax7- and Myf5-negative lineages. While PPARγ is essential for adipogenesis of all fat cells, various transcriptional components play different roles in the development, commitment, and differentiation of white, beige, and brown fat, and PRDM16 has been shown to play an important role in regulating both brown and beige fat (for details, see the text).

Figure 2.

Dual functions of beige fat cells. Beige fat cells have a very low basal level of UCP1 but can robustly respond to cAMP to activate a thermogenic program to levels similar to those seen in the brown cells. When energy intake exceeds energy expenditure, the surplus energy can be stored in beige fat cells in the form of lipid, and beige fat cells take on a more “white” morphology. Many stimuli—including cold, sympathetic stimulation, TZDs, and hormones (including recently identified exercised induced polypeptide irisin)—can activate beige fat cells and result in increased energy dissipation.