Kuorosh Rezaei, Ashley M. Bejoy, Ruxandra D. Rotarescu, Brinley J. Klievik, Adam H. Metherel
{"title":"肝脏特异性 Elovl2-KO 小鼠和对照小鼠摄入 ALA 或 ALA + DHA 后,组织和血液中 n-3 PUFA 水平的性别差异","authors":"Kuorosh Rezaei, Ashley M. Bejoy, Ruxandra D. Rotarescu, Brinley J. Klievik, Adam H. Metherel","doi":"10.1016/j.plefa.2024.102621","DOIUrl":null,"url":null,"abstract":"<div><p>Docosahexaenoic acid (DHA, 22:6n-3) must be consumed from the diet or synthesized from polyunsaturated fatty acid (PUFA) precursors, such as α-linolenic acid (ALA, 18:3n-3). Elongase 2 (encoded by <em>Elovl2</em> gene) catalyzes two elongation reactions in the PUFA biosynthesis pathway and may be important in regulating the observed sex differences in n-3 PUFA levels. Our aim was to determine how targeted knockout of liver <em>Elovl2</em> affects tissue and blood n-3 PUFA levels in male and female C57BL/6J mice. Twenty-eight-day old male and female liver <em>Elovl2</em>-KO and control mice were placed onto one of two dietary protocols for a total of 8 weeks (4–8 mice per genotype, per diet, per sex): 1) an 8-week 2 % ALA in total fat diet or 2) a 4-week 2 % ALA diet followed by a 4-week 2 % ALA + 2 % DHA diet. Following this 8-week feeding period, 12-week-old mice were sacrificed and serum, red blood cells (RBC), liver, heart and brain were collected and fatty acid levels measured. Significant interaction effects (<em>p</em> < 0.05, sex x genotype) for serum, RBC, liver and heart DHA levels were identified. In serum and liver, DHA levels were significantly different (<em>p</em> < 0.01) between all groups with male controls > female controls > female KO > male KO in serum and female controls > male controls > female KO > male KO in liver. In RBCs and the heart, female controls = male controls > female KO > male KO (<em>p</em> < 0.001). The addition of DHA to diet removed the interaction effects on DHA levels in the serum, liver and heart, yielding a significant sex effect in serum, liver (female > male, <em>p</em> < 0.01) and brain (male > female, <em>p</em> < 0.05) and genotype effect in serum and heart (control > KO, <em>p</em> < 0.05). Ablation of liver <em>Elovl2</em> results in significantly lower blood and tissue DHA in a sex-dependent manner, suggesting a role for <em>Elovl2</em> on sex differences in n-3 PUFA levels.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327824000152/pdfft?md5=882d465ce2a8bf1102905cb9c3202a76&pid=1-s2.0-S0952327824000152-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Sex-dependent differences in tissue and blood n-3 PUFA levels following ALA or ALA + DHA feeding of liver-specific Elovl2-KO and control mice\",\"authors\":\"Kuorosh Rezaei, Ashley M. Bejoy, Ruxandra D. Rotarescu, Brinley J. Klievik, Adam H. Metherel\",\"doi\":\"10.1016/j.plefa.2024.102621\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Docosahexaenoic acid (DHA, 22:6n-3) must be consumed from the diet or synthesized from polyunsaturated fatty acid (PUFA) precursors, such as α-linolenic acid (ALA, 18:3n-3). Elongase 2 (encoded by <em>Elovl2</em> gene) catalyzes two elongation reactions in the PUFA biosynthesis pathway and may be important in regulating the observed sex differences in n-3 PUFA levels. Our aim was to determine how targeted knockout of liver <em>Elovl2</em> affects tissue and blood n-3 PUFA levels in male and female C57BL/6J mice. Twenty-eight-day old male and female liver <em>Elovl2</em>-KO and control mice were placed onto one of two dietary protocols for a total of 8 weeks (4–8 mice per genotype, per diet, per sex): 1) an 8-week 2 % ALA in total fat diet or 2) a 4-week 2 % ALA diet followed by a 4-week 2 % ALA + 2 % DHA diet. Following this 8-week feeding period, 12-week-old mice were sacrificed and serum, red blood cells (RBC), liver, heart and brain were collected and fatty acid levels measured. Significant interaction effects (<em>p</em> < 0.05, sex x genotype) for serum, RBC, liver and heart DHA levels were identified. In serum and liver, DHA levels were significantly different (<em>p</em> < 0.01) between all groups with male controls > female controls > female KO > male KO in serum and female controls > male controls > female KO > male KO in liver. In RBCs and the heart, female controls = male controls > female KO > male KO (<em>p</em> < 0.001). The addition of DHA to diet removed the interaction effects on DHA levels in the serum, liver and heart, yielding a significant sex effect in serum, liver (female > male, <em>p</em> < 0.01) and brain (male > female, <em>p</em> < 0.05) and genotype effect in serum and heart (control > KO, <em>p</em> < 0.05). Ablation of liver <em>Elovl2</em> results in significantly lower blood and tissue DHA in a sex-dependent manner, suggesting a role for <em>Elovl2</em> on sex differences in n-3 PUFA levels.</p></div>\",\"PeriodicalId\":94179,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0952327824000152/pdfft?md5=882d465ce2a8bf1102905cb9c3202a76&pid=1-s2.0-S0952327824000152-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0952327824000152\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and essential fatty acids","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0952327824000152","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
二十二碳六烯酸(DHA,22:6n-3)必须从膳食中摄取或从α-亚麻酸(ALA,18:3n-3)等多不饱和脂肪酸(PUFA)前体中合成。伸长酶 2(由 Elovl2 基因编码)催化 PUFA 生物合成途径中的两个伸长反应,可能是调节观察到的 n-3 PUFA 水平性别差异的重要因素。我们的目的是确定肝脏 Elovl2 的定向敲除如何影响雌雄 C57BL/6J 小鼠组织和血液中的 n-3 PUFA 水平。将 28 天大的雌雄肝脏 Elovl2-KO 小鼠和对照组小鼠分别置于两种饮食方案中的一种,共 8 周(每种基因型、每种饮食、每种性别 4-8 只小鼠):1)为期 8 周的 2% ALA 总脂肪饮食;或 2)为期 4 周的 2% ALA 饮食,然后是为期 4 周的 2% ALA + 2% DHA 饮食。喂食 8 周后,宰杀 12 周大的小鼠,收集血清、红细胞 (RBC)、肝脏、心脏和大脑并测量脂肪酸水平。结果发现,血清、红细胞、肝脏和心脏中的 DHA 含量存在显著的交互效应(p < 0.05,性别 x 基因型)。在血清和肝脏中,所有组间的 DHA 水平都有显著差异(p <0.01),血清中为雄性对照组> 雌性对照组> 雌性 KO 组> 雄性 KO 组,肝脏中为雌性对照组> 雄性对照组> 雌性 KO 组> 雄性 KO 组。在红细胞和心脏中,雌性对照组 = 雄性对照组 > 雌性 KO > 雄性 KO(p <0.001)。在饮食中添加 DHA 可消除血清、肝脏和心脏中 DHA 水平的交互效应,从而在血清、肝脏(雌性对照组;雄性对照组,p < 0.01)和大脑(雄性对照组;雌性对照组,p < 0.05)中产生显著的性别效应,在血清和心脏(对照组;KO 组,p < 0.05)中产生基因型效应。肝脏 Elovl2 的消减会导致血液和组织中 DHA 的显著降低,而这一降低是性别依赖性的,这表明 Elovl2 在 n-3 PUFA 水平的性别差异中发挥作用。
Sex-dependent differences in tissue and blood n-3 PUFA levels following ALA or ALA + DHA feeding of liver-specific Elovl2-KO and control mice
Docosahexaenoic acid (DHA, 22:6n-3) must be consumed from the diet or synthesized from polyunsaturated fatty acid (PUFA) precursors, such as α-linolenic acid (ALA, 18:3n-3). Elongase 2 (encoded by Elovl2 gene) catalyzes two elongation reactions in the PUFA biosynthesis pathway and may be important in regulating the observed sex differences in n-3 PUFA levels. Our aim was to determine how targeted knockout of liver Elovl2 affects tissue and blood n-3 PUFA levels in male and female C57BL/6J mice. Twenty-eight-day old male and female liver Elovl2-KO and control mice were placed onto one of two dietary protocols for a total of 8 weeks (4–8 mice per genotype, per diet, per sex): 1) an 8-week 2 % ALA in total fat diet or 2) a 4-week 2 % ALA diet followed by a 4-week 2 % ALA + 2 % DHA diet. Following this 8-week feeding period, 12-week-old mice were sacrificed and serum, red blood cells (RBC), liver, heart and brain were collected and fatty acid levels measured. Significant interaction effects (p < 0.05, sex x genotype) for serum, RBC, liver and heart DHA levels were identified. In serum and liver, DHA levels were significantly different (p < 0.01) between all groups with male controls > female controls > female KO > male KO in serum and female controls > male controls > female KO > male KO in liver. In RBCs and the heart, female controls = male controls > female KO > male KO (p < 0.001). The addition of DHA to diet removed the interaction effects on DHA levels in the serum, liver and heart, yielding a significant sex effect in serum, liver (female > male, p < 0.01) and brain (male > female, p < 0.05) and genotype effect in serum and heart (control > KO, p < 0.05). Ablation of liver Elovl2 results in significantly lower blood and tissue DHA in a sex-dependent manner, suggesting a role for Elovl2 on sex differences in n-3 PUFA levels.