Effects of membrane fatty acid composition on cellular metabolism and oxidative stress in dermal fibroblasts from small and large breed dogs

Abstract

There is ample evidence that cell membrane architecture contributes to metabolism and aging in animals, however the aspects of this architecture that determine the rate of metabolism and longevity are still being debated. The “membrane pacemaker” hypotheses of metabolism and aging, respectively, suggest that increased lipid unsaturation and large amounts of polyunsaturated fatty acids (PUFAs) in cell membranes increases the cellular metabolic rate as well as the vulnerability of the cell to oxidative damage, thus increasing organismal metabolic rate and decreasing longevity. Here, we test these hypotheses by experimentally altering the membrane fatty acid composition of fibroblast cells derived from small and large breed dogs by incubating them in a medium enriched in the monounsaturated fatty acid (MUFA) oleic acid (OA, 18:1) to decrease the total saturation. We then measured cellular metabolic parameters and correlated these parameters with membrane fatty acid composition and oxidative stress. We found that cells from small dogs and OA incubated cells had lower maximal oxygen consumption and basal oxygen consumption rates, respectively, which are traits associated with longer lifespans. Furthermore, although we did not find differences in oxidative stress, cells from small dogs and OA treated cells exhibited reduced ATP coupling efficiency, suggesting that these cells are less prone to producing reactive oxygen species. Membrane fatty acid composition did not differ between cells from large and small dogs, but cells incubated with OA had more monounsaturated fatty acids and a higher number of double bonds overall despite a decrease in PUFAs. Our results suggest that increasing the mono-unsaturation of dog cell membranes may alter some metabolic parameters linked to increases in longevity.