Yes, even human brown fat is on fire!

Abstract

That adult humans possess brown fat is now accepted - but is the brown fat metabolically active? Does human brown fat actually combust fat to release heat? In this issue of the JCI, Ouellet et al. demonstrate that metabolism in brown fat really is increased when adult humans are exposed to cold. This boosts the possibility that calorie combustion in brown fat may be of significance for our metabolism and, correspondingly, that the absence of brown fat may increase our proneness to obesity - provided that brown fat becomes activated not only by cold but also through food-related stimuli.

Figure 1. Location and control of brown adipose tissue in adult humans.

Brown adipose tissue (BAT) is mainly found in depots localized below the clavicles and in the neck (but amount and shape may vary considerably). The activity of the tissue is regulated from the brain, based on the need for heat for body temperature control (as investigated here by Ouellet et al.; ref. 2) (thermoregulatory thermogenesis) or also, probably, on the need for metaboloregulatory thermogenesis. The heat results initially from combustion of stored lipid within the brown adipose tissue (Figure 2), but during prolonged thermogenesis, the components of ingested food are channeled to the tissue as a continuous supply of substrate.

Figure 2. Metabolism in brown adipose tissue.

In the cold, the sympathetic nerves from the brain that innervate brown adipose tissue (Figure 1) are active and release norepinephrine (NE), which stimulates the brown fat cells. This leads to activation of triglyceride breakdown and intracellular release of fatty acids (FA). The fatty acids enter the mitochondria and are degraded through β-oxidation to acetyl-CoA (AcCoA), which enters the citric acid cycle (CAC). Stimulation of the cells by norepinephrine also leads to activation of UCP1, and this allows for the oxidative processes to proceed rapidly, uncoupled from ATP production, i.e., heat is produced. The method used by Ouellet et al. (2) (green) demonstrates increased metabolic activity in brown adipose tissue. A bolus of positron-labeled (¹¹C) acetate (*Ac^–) is injected into the blood and is converted within the cell to acetyl-CoA, which is incorporated into components of the citric acid cycle. When the citric acid cycle rapidly turns over, as happens in stimulated brown fat cells, the labeled carbons are released as CO₂, and the positron label is thus lost from the tissue in proportion to the metabolic activity of the tissue.