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The Regulatory Effects of Diet and Exercise on Glucose Metabolism and Vascular Insulin Signaling in Obese Mice

Undergraduate #124
Discipline: Biological Sciences
Subcategory: Physiology and Health
Session: 3

James R. Ball - University of Missouri
Co-Author(s): Nathan C. Winn, University of Missouri, Columbia, MO; Makenzie L. Woodford, University of Missouri, Columbia, MO; Thomas J. Jurrissen, University of Missouri, Columbia, MO; Jaume Padilla, University of Missouri, Columbia



Obesity-induced insulin resistance often provokes glucose dysmetabolism that increases the risk of cardiometabolic diseases, with the vasculature being highly susceptible to glucose toxicity and insulin resistance. Notably, lifestyle interventions including diet and exercise have been shown to improve obesity-associated insulin resistance and glycemic control. However, it is largely unknown whether enhanced glucose homeostasis caused by daily exercise and low-fat diet (LFD) is tightly linked with improved vascular insulin signaling in diet-induced obese mice. Herein, five-week-old female mice (CL57BL/6J) were fed either a (LFD) or a Western diet (WD) for 9 weeks to provoke obesity and insulin resistance. At 14 weeks of age, WD-fed mice were randomized to one of the following groups (n=9-10/group): WD; WD + voluntary wheel running (WD WR); or LFD, where mice were switched from a WD to a LFD. At 14 weeks of age, WD-fed mice had greater adiposity and were glucose intolerant relative to LFD-fed mice, demonstrating an obesogenic phenotype. At 24 weeks of age, WD mice gained more weight than WD WR and LFD mice, respectively. Compared to WD animals, obesity-induced glucose intolerance was attenuated in both WD WR and LFD groups, with the LFD group having greater improvements than WD WR. In the abdominal aorta, ex vivo insulin-induced phosphorylation of the major signaling node, Akt, was significantly augmented in LFD mice, with no differences between WD and WD WR animals. Collectively, these data suggest that both daily activity and low-fat diet enhance glucose homeostasis in diet-induced obese mice, whereas the magnitude of improvement is greater in low-fat diet mice. Furthermore, only low-fat diet significantly improved vascular insulin signaling which may be attributed to less adiposity and better glycemic control.

Funder Acknowledgement(s): NIH IMSD EXPRESS Fellows Program R25GM056901

Faculty Advisor: Jaume Padilla, padillaja@missouri.edu

Role: I assisted my graduate student in helping to take care of these animals throughout the study. I also ran western blots in order to help asses the phosphorylation of Akt in the abdominal aorta and other proteins that will be included on my poster. Additionally, I conducted PCR to measure the gene expression of our genes of interest and I helped analyze and quantify the data we received from these experiments.

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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