Thermogenic Capacity of Human Supraclavicular Brown Fat and Cold-Stimulated Brain Glucose Metabolism

Metabolites. 2023 Mar 5;13(3):387. doi: 10.3390/metabo13030387.

Abstract

Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of UCP-1, which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress. Ten healthy human participants underwent 18F-FDG PET scanning of the brain under cold stimulus to determine brain glucose uptake (BGU). On a separate day, an excision biopsy of the supraclavicular fat-the fat proximal to the carotid arteries supplying the brain with warm blood-was performed to determine the mRNA expression of the thermogenic protein UCP-1. Expression of UCP-1 in supraclavicular BAT was directly related to the whole brain glucose uptake rate determined under cold stimulation (rho = 0.71, p = 0.03). In sub-compartmental brain analysis, UCP-1 expression in supraclavicular BAT was directly related to cold-stimulated glucose uptake rates in the hypothalamus, medulla, midbrain, limbic system, frontal lobe, occipital lobe, and parietal lobe (all rho ≥ 0.67, p < 0.05). These relationships were independent of body mass index and age. When analysing gene expressions of BAT secretome, we found a positive correlation between cold-stimulated BGU and DIO2. These findings provide evidence of functional links between brain metabolism under cold stimulation and UCP-1 and DIO2 expressions in BAT in humans. More research is needed to evaluate the importance of these findings in clinical outcomes, for instance, in examining the supporting role of BAT in cognitive functions under cold stress.

Keywords: BAT; UCP-1; brain metabolism; cold stimulation; human brown adipose tissue; thermogenesis.

Grants and funding

The study was financially supported by the Academy of Finland (259926, 265204), the Paulo Foundation, the Finnish Cultural Foundation Southwest Finland Regional Funds, the Finnish Cultural Foundation Central Funds, the Turku University Hospital Research Funds, the European Union (EUFP7 project 278373; DIABAT), the Finnish Medical Foundation, Finnish Diabetes Research Foundation, Finnish-Norwegian Medical Research Foundation, Juhani Aho Foundation for Medical Research, Jalmari ja Rauha Ahokkaan Säätiö. T.F. and M.K. are funded by the German Research Foundation (BATenergy TRR333/1, Deutsche Forschungsgemeinschaft, DFG).