Brown and Beige Fat: Molecular Parts of a Thermogenic Machine

Abstract

The epidemic of obesity and type 2 diabetes has increased interest in pathways that affect energy balance in mammalian systems. Brown fat, in all of its dimensions, can increase energy expenditure through the dissipation of chemical energy in the form of heat, using mitochondrial uncoupling and perhaps other pathways. We discuss here some of the thermodynamic and cellular aspects of recent progress in brown fat research. This includes studies of developmental lineages of UCP1(+) adipocytes, including the discovery of beige fat cells, a new thermogenic cell type. We also discuss the physiology and transcriptional control of brown and beige cells in rodents and the state of current knowledge about human brown fat.

Figure 1

Schematic of adaptive thermogenesis in brown and beige adipocytes. This process is typically thought of as being indirectly activated by cold, via the sympathetic nervous system (SNS). Catecholamines stimulate β-adrenergic receptors (βAR), ultimately activating UCP1-dependent thermogenesis. Adaptive thermogenesis can also be activated directly by cold in beige adipocytes and by other stimuli that may signal independently from the β-adrenergic receptors. The reducing equivalents generated by the tricarboxylic acid (TCA) cycle enter the ETC. This generates a proton gradient across the inner mitochondrial membrane. Instead of linking this gradient to ATP synthesis via complex V, UCP1 is able to uncouple this gradient with the chemical energy converted to heat.