Linoleic Acid-Rich Diet Improves Glucose Clearance, Increases Grip Strength, and Alters Skeletal Muscle Cardiolipin Species in a Mouse Model of Diet-Induced Obesity

OBJECTIVES: Compare the effects of high-fat diets containing linoleic-acid (LA)-rich oil and lard on measures of whole-body energy metabolism and skeletal muscle function in a mouse model of diet-induced obesity. METHODS: 9-week old male C57BL6/J mice (n = 24) were assigned to high fat isocaloric diets (24% fat by wt) containing LA-rich safflower oil (SO) or lard (LD) for 18 weeks. Food intake and body weight were measured every 2 days. EchoMRI was used at Days 0, 65, and 100 to determine the effects of each diet on body composition. Grip strength was measured to assess muscle strength at Day 113. Fasting blood glucose was measured and an insulin tolerance test (ITT) was performed on Day 85 to measure insulin sensitivity and glucose uptake. After 130 days, quadriceps muscle mitochondrial and cardiolipin remodeling gene expression was measured by qRT-PCR. Cardiolipin (CL) speciation of muscle was measured by normal phase liquid chromatography coupled to electrospray ionization mass spectrometry. RESULTS: Although LD-fed mice gained body mass at a faster rate, there was no difference in body mass or cumulative food intake after 130 days. Similarly, % adiposity of LD-fed mice increased at Day 65 compared to those fed the SO diet, but not at Day 100. Mice consuming the SO diet exhibited increased hindlimb grip strength. SO-fed mice exhibited lower blood glucose levels at 90 and 120 minutes post-insulin injection, demonstrating improved glucose clearance over time. Significant differences in CL speciation, particularly that of LA-containing species, were observed. CONCLUSIONS: When compared to the LD diet, mice consuming the SO diet exhibited early reductions in adiposity that were undistinguishable after 130 days of dietary intervention. However, mice fed SO diet exhibited improved grip strength, insulin-stimulated glucose clearance and significant differences in skeletal muscle cardiolipin speciation. Future studies will address the relationship between LA-derived metabolites, CL speciation, and improved muscle function. FUNDING SOURCES: Funding was provided by NIH, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship. DBS received support from the AOCS Thomas H. Smouse Memorial Fellowship.