Kuorosh Rezaei, Ashley M. Bejoy, Ruxandra D. Rotarescu, Brinley J. Klievik, Adam H. Metherel
{"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}
引用次数: 0
Abstract
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.