Effects of membrane fatty acid composition on cellular metabolism and oxidative stress in dermal fibroblasts from small and large breed dogs
Effects of membrane fatty acid composition on cellular metabolism and oxidative stress in dermal fibroblasts from small and large breed dogs
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DOI：
10.1242/jeb.221804
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发表时间：
2020-06-01
影响因子：
2.8
通讯作者：
Champagne, Alex M.
中科院分区：
文献类型：
--
作者：
Jimenez, Ana Gabriela;Winward, Joshua D.;Champagne, Alex M.
有充分的证据表明，细胞膜结构有助于动物的新陈代谢和衰老：然而，这种结构的方面，决定新陈代谢和寿命的速度仍在争论中。代谢和衰老的“膜起搏器”假说分别表明，细胞膜中脂质不饱和度的增加和大量多不饱和脂肪酸（PUFA）增加了细胞代谢率以及细胞对氧化损伤的脆弱性，从而增加了生物体代谢率并降低了寿命。在这里，我们通过实验改变来自小型和大型品种犬的成纤维细胞的膜脂肪酸组成来测试这些假设，方法是将它们在富含单不饱和脂肪酸（MUFA）油酸（OA，18：1）的培养基中孵育，以降低总饱和度。然后，我们测量细胞代谢参数，并将这些参数与膜脂肪酸组成和氧化应激相关。我们发现，来自小型犬的细胞和OA孵育的细胞分别具有较低的最大耗氧量和基础耗氧量，这是与较长寿命相关的特征。此外，虽然我们没有发现氧化应激的差异，但来自小型犬的细胞和OA处理的细胞表现出降低的ATP偶联效率，表明这些细胞不太容易产生活性氧。膜脂肪酸组成没有不同的细胞从大型和小型犬，但OA孵育的细胞有更多的单不饱和脂肪酸和较高数量的双键的整体，尽管PUFA减少。我们的研究结果表明，增加狗细胞膜的单不饱和度可能会改变一些与寿命增加有关的代谢参数。
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' hypothesis of metabolism and of aging, respectively, suggest that increased lipid unsaturation and large amounts of polyunsaturated fatty acids (PUFAs) in cell membranes increase 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 tested 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 monounsaturation of dog cell membranes may alter some metabolic parameters linked to increases in longevity.