Human and Mouse Brown Adipose Tissue Mitochondria Have Comparable UCP1 Function

Abstract

Summary Brown adipose tissue (BAT) plays an important role in mammalian thermoregulation. The component of BAT mitochondria that permits this function is the inner membrane carrier protein uncoupling protein 1 (UCP1). To the best of our knowledge, no studies have directly quantified UCP1 function in human BAT. Further, whether human and rodent BAT have comparable thermogenic function remains unknown. We employed high-resolution respirometry to determine the respiratory capacity, coupling control, and most importantly, UCP1 function of human supraclavicular BAT and rodent interscapular BAT. Human BAT was sensitive to the purine nucleotide GDP, providing the first direct that human BAT mitochondria have thermogenically functional UCP1. Further, our data demonstrate that human and rodent BAT have similar UCP1 function per mitochondrion. These data indicate that human and rodent BAT are qualitatively similar in terms of UCP1 function.

Identification and characterization of a supraclavicular brown adipose tissue in mice

“…Specifically, given that scBAT surrounds the jugular veins of the neck, the primary function of mouse scBAT could likely be to keep the blood vessels (veins) supplying circulation between the brain and heart warm, while iBAT and subscapular BAT keep the blood vessels responsible for circulation in the torso warm. In support of this notion, scBAT was also recently found near the jugular vein in humans (35). Together with previously identified deep neck BAT depots in the carotid sheath, where the common carotid artery and internal jugular vein are located (18), human neck BAT likely maintains the temperature of the circulatory system delivering blood to and from the brain.…”

“…In addition, we found that two newly identified human scBAT markers, Kcnk3 and Mtus1, were also expressed in mouse scBAT. Kcnk3 is highly expressed in mouse iBAT (44,45), in human scBAT and deep neck BAT (26,35), and in mouse beige adipocytes (26), suggesting that Kcnk3, like Lhx8 and Tbx1, is not specifically expressed in one type of adipose tissue. Nevertheless, the observation that Kcnk3, Mtus1, Lhx8, and Tbx1 are all expressed in mouse scBAT provides molecular evidence that mouse scBAT is similar to human scBAT.…”

Mapping of human brown adipose tissue in lean and obese young men

“…Studies suggest that BAT may be responsible for up to one-third, or even more (37), of overall metabolic rate in some cold-acclimated species (38) while accounting for <2% of total body mass (33). In addition, rodent brown adipocytes appear to have similar cellular physiology and thermogenic capacity as human brown adipocytes (3,39). In warm-acclimated rats, BAT can generate 112 cal/g*d (40).…”

“…Conversely, brown adipose tissue (BAT) is a thermogenic tissue responsible for producing energy in the form of heat (1). In contrast to the homogeneous classical BAT seen in rodents, human BAT is composed of stromal tissue, white adipocytes (2,3), and uncoupling protein-1 (UCP1)-containing thermogenic adipocytes of two different lineages (4): "brown" (5) and "beige (2)/brite" (6). BAT takes up plasma glucose and free fatty acids in response to mild cold exposure (7)(8)(9).…”

Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1–Deficient Mice

“…Mitochondrial uncoupling protein 1 (UCP1) endows both human and mouse brown adipocytes with thermogenic capacity (6). It is widely assumed that BAT 18 F-FDG uptake provides an indirect quantitative measure of thermogenesis.…”