Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans

Abstract

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species—in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice

“…In this context, a recent study in human adipose tissue has revealed that the presence of active BAT is positively associated with an anti‐inflammatory oxylipins/eicosanoids profile 70 . Similarly, EPA and DHA have been recently associated with the levels of BAT activity in humans 71 . A lipidomic analysis of BAT in young mice showed that phospholipids and free fatty acids were more abundant in BAT than in WAT, and that phospholipids in BAT were mostly composed of PUFAs, especially DHA 72 …”

“…70 Similarly, EPA and DHA have been recently associated with the levels of BAT activity in humans. 71 A lipidomic analysis of BAT in young mice showed that phospholipids and free fatty acids were more abundant in BAT than in WAT, and that phospholipids in BAT were mostly composed of PUFAs, especially DHA. 72 Our study shows that chronic dietary supplementation with DHA was able to reverse the drop in the sum of SPMs observed in BAT of aged DIO mice, reaching even values significantly higher than those found in BAT of young mice.…”

Brown Adipose Tissue: New Challenges for Prevention of Childhood Obesity. A Narrative Review

“…Some epigenetic factors could also underlie the activation of BAT by omega-3 [ 190 ]. In humans there are conflicting results that showed a reduction in waist circumference and accumulation of adipose tissue during growth, but the mechanism remains unclear [ 205 ]. NEFAs could be possible biomarkers of BAT activity [ 206 ], but several humans studies are needed to fully elucidate associations between BAT and NEFAs circulating levels.…”

“…Recently, associations between BAT and circulating levels of certain lipid species (classes of non-esterified fatty acids, NEFAs, and oxylipin lipids) have been identified in mice [ 205 ]. In humans, a decrease in weight gain and an increase in BAT activity following high dietary omega-3 intake (from fish or fish oil supplementation recorded by validated semiquantitative food frequency questionnaire) has been observed only in genetically driven, high-number cohort studies and not in clinical trials [ 206 ].…”

“…In humans, a decrease in weight gain and an increase in BAT activity following high dietary omega-3 intake (from fish or fish oil supplementation recorded by validated semiquantitative food frequency questionnaire) has been observed only in genetically driven, high-number cohort studies and not in clinical trials [ 206 ]. A direct mechanistic role of EPA and DHA in the up-regulation of BAT activity in humans to date is supported by preclinical studies [ 175 , 193 , 194 , 207 , 208 , 209 ]; however, possible biomarkers of BAT activity could be the indirect relationships as a result of NEFA oxidation [ 205 ]. To fully elucidate the relationship between omega-3 NEFAs and BAT activity, further human studies are needed, including NEFA interventions and tracers.…”