'Royal College of Obstetricians & Gynaecologists (RCOG)'
Abstract
Brown adipose tissue (BAT) dysfunction in aging and obesity has been related to
chronic unresolved inflammation, which could be mediated by an impaired production
of specialized proresolving lipid mediators (SPMs), such as Lipoxins-LXs,
Resolvins-Rvs,
Protectins-PDs,
and Maresins-MaRs.
Our aim was to characterize the
changes in BAT SPMs signatures and their association with BAT dysfunction during
aging, especially under obesogenic conditions, and their modulation by a docosahexaenoic
acid (DHA)-rich
diet. Lipidomic, functional, and molecular studies were performed
in BAT of 2-and
18-month-
old
lean (CT) female mice and in 18-month-
old
diet-induced
obese (DIO) mice fed with a high-fat
diet (HFD), or a DHA-enriched
HFD. Aging downregulated Prdm16 and UCP1 levels, especially in DIO mice,
while DHA partially restored them. Arachidonic acid (AA)-derived
LXs and DHA-derived
MaRs and PDs were the most abundant SPMs in BAT of young CT mice.Interestingly, the sum of LXs and of PDs were significantly lower in aged DIO mice
compared to young CT mice. Some of the SPMs most significantly reduced in obese-aged
mice included LXB4, MaR2, 4S,14S-diHDHA,
10S,17S-diHDHA
(a.k.a. PDX),
and RvD6. In contrast, DHA increased DHA-derived
SPMs, without modifying LXs.
However, MicroPET studies showed that DHA was not able to counteract the impaired
cold exposure response in BAT of obese-aged
mice. Our data suggest that a
defective SPMs production could underlie the decrease of BAT activity observed in
obese-aged
mice, and highlight the relevance to further characterize the physiological
role and therapeutic potential of specific SPMs on BAT development and function