Dietary fat quality impacts metabolic impairments of type 2 diabetes risk differently in male and female CD-1® mice

Metabolic impairments associated with type 2 diabetes, including insulin resistance and loss of glycemic control, disproportionately impact the elderly. Lifestyle interventions, such as manipulation of dietary fat quality (i.e., fatty acid (FA) composition), have been shown to favorably modulate metabolic health. Yet, whether or not chronic consumption of beneficial FAs can protect against metabolic derangements and disease risk during aging is not well-defined. We sought to evaluate whether long-term dietary supplementation of fish-, dairy-, or echium-derived FAs to the average FA profile in a U.S. American diet may offset metabolic impairments in males and females during aging. One-month-old CD-1® mice were fed isoenergetic, high-fat (40%) diets with the fat content comprised of either 100% control fat blend (CO) or 70% CO with 30% fish oil, dairy fat, or echium oil for 13 months. Every three months, parameters of glucose homeostasis were evaluated via glucose and insulin tolerance tests. Glucose tolerance improved in males consuming a diet supplemented with fish oil or echium oil as aging progressed, but not in females. Yet, females were more metabolically protected than males regardless of age. Additionally, Spearman correlations were performed between indices of glucose homeostasis and previously reported measurements of diet-derived FA content in tissues and colonic bacterial composition, which also revealed sex-specific associations. This study provides evidence that long-term dietary fat quality influences risk factors of metabolic diseases during aging in a sex-dependent manner, thus, sex is a critical factor to be considered in future dietary strategies to mitigate type 2 diabetes risk.

Incorporation of Fatty Acids as a Biomarker of Dietary Intake and Source is Fatty Acid and Blood Fraction Specific in CD-1 Mice

Objectives Accurate biomarkers of fatty acid (FA) intake and source (e.g., diet-derived FA) are an important assessment tool to study the role of dietary fat quality on metabolic health. The purpose of this study was to assess the incorporation of unique, dietary FA from fish oil, echium oil, and dairy fat into the red blood cell membranes (RBCM), plasma phospholipids (PPL), and plasma cholesterol esters (PCE) of genetically-outbred CD-1 mice. Methods At one month of age, mice were assigned to one of four isocaloric diets consisting either of a control fat blend or the control fat blend supplemented (30%) with fish oil, echium oil, or dairy fat (n = 10/diet/sex). After 52 weeks of feeding, cardiac blood was collected for FA analysis of RBCM, PPL, and PCE using gas-liquid chromatography. Results Expectedly, a higher proportion of fish-derived FA (eicosapentaenoic acid and docosahexaenoic acid) was observed in the RBCM and PCE of fish oil-fed mice (P < 0.0001). Accordingly, a greater proportion of echium oil-derived γ-linolenic acid was incorporated into all blood fractions of echium oil-fed mice (P < 0.0001). Yet, stearidonic acid, specific to echium oil, was not detected in the RBCM of mice, and no differences in the proportion of stearidonic acid were found in the PPL and PCE. Odd-chain FA (pentadecanoic acid and heptadecanoic acid) were not exclusively enriched in the blood fractions of dairy-fed mice. Conversely, trans-palmitoleic acid, vaccenic acid, rumenic acid, and branched-chain FA were differentially incorporated into the PPL and PCE, while not detected in the RBCM. Conclusions In summary, unique, diet-derived FA are differentially incorporated into the blood fractions of mice, indicating that the incorporation of dietary FA into blood fractions is highly dependent upon the FA species. Therefore, diet-derived FA cannot be used universally as a reliable biomarker to validate dietary FA source in mice, rather, the specific FA and blood fraction must be carefully considered. Funding Sources Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1,006,628).

Single-Dose SDA-Rich Echium Oil Increases Plasma EPA, DPAn3, and DHA Concentrations

The omega-3 (n3) polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with health benefits. The primary dietary source of EPA and DHA is seafood. Alpha-linoleic acid (ALA) has not been shown to be a good source for EPA and DHA; however, stearidonic acid (SDA)—which is naturally contained in echium oil (EO)—may be a more promising alternative. This study was aimed at investigating the short-term n3 PUFA metabolism after the ingestion of a single dose of EO. Healthy young male subjects (n = 12) ingested a single dose of 26 g of EO after overnight fasting. Plasma fatty acid concentrations and relative amounts were determined at baseline and 2, 4, 6, 8, 24, 48, and 72 h after the ingestion of EO. During the whole examination period, the participants received standardized nutrition. Plasma ALA and SDA concentrations increased rapidly after the single dose of EO. Additionally, EPA and DPAn3 concentrations both increased significantly by 47% after 72 h compared to baseline; DHA concentrations also significantly increased by 21% after 72 h. To conclude, EO increases plasma ALA, SDA, EPA, DPAn3, and DHA concentrations and may be an alternative source for these n3 PUFAs.

Incorporation of Unique, Diet-derived Fatty Acids into Hepatic Tissue Is Associated with Improved Glucose Homeostasis in Aged CD-1 Mice (OR24-02-19)

Objectives We hypothesized that the chronic consumption of unique dietary FA derived from dairy fat and echium oil, respectively, would affect the FA composition and content of the hepatic tissue and correlate with parameters of glucose homeostasis in an aged, genetically heterogeneous mouse population. Our objectives were to i) measure glucose homeostasis, ii) determine the FA composition of hepatic tissue, and iii) correlate physiologic data and hepatic FA content by diet and sex. Methods From one month of age, CD-1 male and female mice (n = 10/diet/sex) were fed either a high-fat (40% total energy) control diet comprising of the FA composition of the typical U.S. American diet (CO), or an isoenergetic diet with 30% of CO fat replaced with dairy fat (BO) or echium oil (EO) for the study duration of 13 months. Every three months, whole-body glucose homeostasis was assessed (i.e., glucose tolerance and insulin tolerance tests (GTT and ITT, respectively)). At the end of the study, hepatic tissue was collected and analyzed for FA composition via gas-liquid chromatography. Results Hepatic content of stearidonic acid (SDA; 18:4 n-3) and γ-linolenic acid (18:3 n-6) was greatest in EO-fed mice (P < .0001). Mice fed a BO-diet had the greatest hepatic content of total odd- and branched-chain FA (OBCFA) and conjugated linoleic acids (P < .0001), as well as a greater hepatic content of 18:1 isomers compared to EO-fed mice (P < .001). In EO-fed females, hepatic content of SDA correlated with improved glucose tolerance, as determined by GTT area under the curve (r = −.94; P < 0.01), and in EO-fed males, hepatic content of SDA was positively associated with improved insulin sensitivity (r = .79; P < 0.05). In BO-fed males, hepatic content of total OCFA was negatively correlated with fasting plasma insulin levels (r = −.83; P < 0.05), and hepatic content of total iso BCFA was associated with improved insulin sensitivity (r = −.89; P < 0.05). Conclusions These findings demonstrate that habitual consumption of unique FA derived from dairy fat and echium oil influences hepatic FA composition and content and correlates with improvements in whole-body glucose homeostasis in an aged population. Furthermore, this study suggests that dietary fat quality may be part of an effective preventative strategy for metabolic diseases such as T2D in the elderly. Funding Sources Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1006628).