Tissue and Circulating Fatty Acids as Biomarkers to Evaluate Long-Term Fat Intake Are Tissue and Sex Dependent in CD-1 Mice

Background: There is currently no consensus on which tissues are optimal for assessing specific diet-derived fatty acids (FAs) as biomarkers for long-term dietary studies. Objectives: This study measured the content of unique diet-derived FAs from dairy, echium, and fish in tissues (adipose, muscle, liver, erythrocyte membranes, and plasma phospholipids, cholesterol esters, triglycerides, and free fatty acids) after long-term feeding in CD-1 mice. Methods: Beginning at weaning, mice (n = 10-11/sex/diet) were fed 1 of 4 diets (40% kcal/total energy) that only differed in FA composition: control fat blend (CON), reflecting the FA profile of the average US American diet, or CON supplemented with 30% of fish oil (FO), dairy fat (DF), or echium oil (EO). After 13 mo, tissues were collected to determine FAs via gas-liquid chromatography. Tissue FAs were analyzed via 2-factor ANOVA, and relationships between FA intake and tissue content were assessed with Spearman correlations. Results: As anticipated, 20:5n-3 (ω-3) tissue content was ≤32-fold greater in FO- compared with CON-fed mice (P < 0.05). In addition, 20:5n-3 intake strongly correlated with its content in all tissues (ρ = 0.67-0.76; P < 0.05). Echium oil intake also influenced tissue FA content in mice as expected. For example, 18:3n-6 was ≤25-fold greater in adipose, muscle, and liver tissues of EO-fed compared with CON-fed mice (P < 0.05). Tissue content of FAs typically considered biomarkers of dairy fat intake (15:0, 16:1 t9, and 17:0) was often not greater in mice fed DF than other diet groups, although 18:2 c9, t11 content was ≤6-fold greater in tissues from DF-fed compared with CON-fed mice (P < 0.05). The content of dairy-derived FAs in blood fractions of females was up to 2-fold greater compared with males, whereas docosapentaenoic acid content was up to 1-fold greater in all blood fractions and in liver tissue of males compared with females (P < 0.05). In adipose, muscle, and liver tissue, the content of γ-linolenic acid and stearidonic acid was less than 1-fold greater in females than in males (P < 0.05). Conclusions: Our study indicates that the distribution of dietary FAs is tissue and sex dependent in aged CD-1 mice. Research using FA biomarkers should assess a combination of FA biomarkers to accurately validate patterns of FA intake and source.