National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Department of Nutrition, School of Public Health, Department of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.
Eur J Nutr. 2023 Jun;62(4):1867-1878. doi: 10.1007/s00394-023-03120-0. Epub 2023 Mar 1.
Previous evidence indicated anti-ageing potential of docosahexaenoic acid (DHA), but the underlying mechanism remains unclear. We investigated protective effect of DHA on telomere attrition and lipid disturbance in male mice with premature ageing caused by telomerase deficiency.
Wild-type (WT) and fourth-generation telomerase-deficient (G4 Terc, Terc knockout, KO) male mice (C57BL/6, 2 months old) were fed control diet (WT-C and KO-C groups) or DHA-enriched diet containing 0.80% DHA by weight (WT-DHA and KO-DHA groups) for 10 months. The ageing phenotypes and metabolic level [carbon dioxide emission, oxygen consumption, and respiratory exchange ratio (RER)] were assessed at the end of the experiment. Telomere length in various tissues and the hepatic gene and protein expression for regulating lipid synthesis and lipolysis were measured. Data were tested using one- or two-factor ANOVA.
In KO male mice, DHA prevented weight loss, corrected high RER, and reduced fat loss. Telomere shortening was reduced by 22.3%, 25.5%, and 13.5% in heart, liver, and testes of the KO-DHA group compared with those in the KO-C group. The KO-DHA group exhibited higher gene transcription involved in glycerol-3-phosphate pathway [glycerol-3-phosphate acyltransferase (Gpat)], lower gene expression of β-oxidation [carnitine palmitoyltransferase 1a (Cpt1a)], and upregulation of proteins in lipid synthesis [mammalian target of rapamycin complex 1 (mTORC1) and sterol responsive element binding protein 1 (SREBP1)] in liver than the KO-C group.
Long-term DHA intervention attenuates telomere attrition and promotes lipid synthesis via the tuberous sclerosis complex 2 (TSC2)-mTORC1-SREBP1 pathway in KO male mice.
先前的证据表明二十二碳六烯酸（DHA）具有抗衰老潜力，但潜在机制尚不清楚。我们研究了 DHA 对端粒酶缺陷导致的雄性小鼠过早衰老引起的端粒磨损和脂质紊乱的保护作用。
野生型（WT）和第四代端粒酶缺陷型（G4 Terc，Terc 敲除，KO）雄性小鼠（C57BL/6，2 个月龄）分别喂食对照饮食（WT-C 和 KO-C 组）或富含 0.80% DHA 的饮食（WT-DHA 和 KO-DHA 组）10 个月。实验结束时评估衰老表型和代谢水平[二氧化碳排放、耗氧量和呼吸交换率（RER）]。测量各种组织中的端粒长度以及调节脂质合成和脂肪分解的肝基因和蛋白质表达。数据采用单因素或双因素方差分析进行检验。
在 KO 雄性小鼠中，DHA 可防止体重减轻、纠正高 RER 并减少脂肪损失。与 KO-C 组相比，KO-DHA 组心脏、肝脏和睾丸的端粒缩短减少了 22.3%、25.5%和 13.5%。KO-DHA 组肝脏中甘油-3-磷酸途径[甘油-3-磷酸酰基转移酶（Gpat）]相关基因转录较高，β-氧化[肉碱棕榈酰转移酶 1a（Cpt1a）]相关基因表达较低，脂质合成相关蛋白[雷帕霉素复合物 1 靶蛋白（mTORC1）和固醇调节元件结合蛋白 1（SREBP1）]上调。
长期 DHA 干预通过结节性硬化复合物 2（TSC2）-mTORC1-SREBP1 通路减轻 KO 雄性小鼠的端粒磨损并促进脂质合成。
