Date of Completion

2014

Document Type

Thesis

Department

College of Medicine

Faculty Advisor/Sponsor

Tom Jetton

Second Advisor

Dhananjay Gupta

Third Advisor

Jana Kraft

Keywords

Omega-3 Fatty Acids, Echium Oil, Diabetes, Insulin Signal Transduction in Skeletal Muscle, Glucose Metabolism, Unfolded Protein Respose

Abstract

Skeletal muscle mediates 70-80% of glucose uptake. When the skeletal muscle’s capability to absorb glucose is reduced, the individual becomes insulin resistant and develops, if unabated, diabetes. Here we performed a high fat feeding study on inbred diet-induced obesity in C57BL/6 (B6) mice over the course of 12 weeks, in which we compared the well-established effects of omega-3 fatty acid (n-3) rich fish oil (FO) versus the poorly understood effects of balanced n-3 and omega-6 fatty acid (n-6) rich plant derived Echium oil (EO). Although there were little differences in HFEO or HFFO supplemented groups compared to the high fat control group with respect to blood glucose or plasma insulin concentrations, the Echium oil-enriched diet improved glucose tolerance by 12 weeks. Skeletal muscle was examined for diet-specific changes in insulin sensitivity, growth and survival signaling, and anti-inflammatory activity. We found that the n-3 supplemented high fat diet-fed mice, and especially the HFEO group, showed enhanced Akt1 activity, as well as increased GSK-3β phosphorylation and inactivation in the HFEO group, suggesting increased insulin signaling and glycogen synthesis. Although skeletal muscle PPARγ levels were not different among the high fat diet groups, BiP, a marker of ER stress, had a trend of being reduced in the HFEO group. Thus, the improved glucose tolerance of Echium oil-supplemented high fat diet-fed mice were due to changes in skeletal muscle physiology resulting in enhanced insulin sensitivity and reduced ER stress.

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