Cold exposure–induced alterations in n-3 fatty acid profiles and their associations with brown adipose tissue activity

Abstract

Brown adipose tissue (BAT) contributes to energy expenditure through cold-induced thermogenesis and is closely linked to systemic lipid metabolism. However, the dynamic changes in circulating n-3 polyunsaturated fatty acids (PUFAs) during cold exposure and their association with BAT activity remain unclear. Healthy young men underwent controlled cold exposure, and BAT activity was quantified using fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Circulating levels of n-3 PUFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were measured before and after cold exposure using whole-blood lipidomics. K-means clustering based on log-transformed maximum standardized uptake value (lnSUVmax) was performed. Changes in lipid parameters were evaluated using paired t-tests and multiple regression analyses. Cold exposure significantly decreased ALA levels and the ALA/EPA ratio while increasing EPA and DPA levels and the EPA/DPA and DPA/DHA ratios. Multiple regression analyses revealed that BAT activity (lnSUVmax) was independently associated with changes in several lipid parameters. Higher SUVmax was positively associated with changes in ALA levels and the ALA/EPA ratio, whereas inverse associations were observed with changes in EPA, DPA, EPA/DPA, and DPA/DHA. Baseline lipid levels were not significant predictors of lipidomic changes. Cold-induced BAT activation is associated with dynamic remodeling of circulating n-3 fatty acids. These findings suggest that thermogenic capacity may influence systemic lipid metabolism and highlight the metabolic interplay between BAT activity and circulating n-3 PUFAs. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000029206.