UCP1 in Brite/Beige Adipose Tissue Mitochondria Is Functionally Thermogenic

The phenomenon of white fat “browning,” in which certain white adipose tissue depots significantly increase gene expression for the uncoupling protein UCP1 and thus supposedly acquire thermogenic, fat-burning properties, has attracted considerable attention. Because the mRNA increases are from very low initial levels, the metabolic relevance of the change is unclear: is the UCP1 protein thermogenically competent in these brite/beige-fat mitochondria? We found that, in mitochondria isolated from the inguinal “white” adipose depot of cold-acclimated mice, UCP1 protein levels almost reached those in brown-fat mitochondria. The UCP1 was thermogenically functional, in that these mitochondria exhibited UCP1-dependent thermogenesis with lipid or carbohydrate substrates with canonical guanosine diphosphate (GDP) sensitivity and loss of thermogenesis in UCP1 knockout (KO) mice. Obesogenic mouse strains had a lower thermogenic potential than obesity-resistant strains. The thermogenic density (UCP1-dependent oxygen consumption per g tissue) of inguinal white adipose tissue was maximally one-fifth of interscapular brown adipose tissue, and the total quantitative contribution of all inguinal mitochondria was maximally one-third of all interscapular brown-fat mitochondria, indicating that the classical brown adipose tissue depots would still predominate in thermogenesis. [Display omitted] •In recruited brite/beige-fat mitochondria, UCP1 protein is present in functional amount•UCP1 is canonically regulated and thermogenically competent with regular substrates•UCP1-mediated thermogenic capacity is lower in obesogenic C57Bl/6 than in 129Sv mice•Total brite adipose tissue UCP1-mediated thermogenic capacity is low at a systemic level There is great interest in the phenomenon of white fat “browning”; i.e., the appearance of the uncoupling protein UCP1 in white fat depots, supposedly bestowing the white fat with thermogenic, fat-burning properties. However, there has been little evidence that the UCP1 in the white fat is functional. Here, Nedergaard and colleagues clearly show that the white-fat UCP1 as such is truly thermogenic. However, the combined functional effect of the UCP1 in the browned white fat is still only a fraction of that in the brown fat.