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

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. 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. 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). 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. Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1006628).