Chad Hancock, Nutrition, Dietetics & Food Science
Evaluation of progress on research objectives
Evaluation of progress on research objectives
The purpose of the research proposed in this MEG grant was to examine the relationship between the role of AMPK and LKB1 on the adaptations that occur in response to iron deficiency. We made significant progress for several aspects of the proposal. Our first approach was to examine 5’AMP-activated protein kinase (AMPK) activation in rat skeletal muscle during iron deficiency. As a cellular energy sensor, AMPK is activated in response to energy stresses such as hypoxia and muscle contraction. To determine effects of iron deficiency on AMPK activation and signaling, as well as the AMPK subunit composition in skeletal muscle, rats were fed a control (C=50-58 mg/kg Fe) or iron deficient (ID=2-6 mg/kg Fe) diet for 6–8 wks. From this work we demonstrated that chronic iron deficiency causes a shift in the expression of AMPK subunit composition. AMPK is composed of three subunits (α, β, and γ) which each have different isoforms. Iron deficiency also causes chronic activation of AMPK as well as an increase in AMPKa1 activity in exercised skeletal muscle.
Following this work, we examined iron deficiency in the context of a transgenic mouse model. LKB1 (the upstream activator of AMPK) knockout mice were used to determine if the capacity to activate AMPK would further exacerbate problems associated with iron deficiency. This part of the proposal involved a great deal of work that didn’t result in the expected research outcomes that we had anticipated. The mice placed on the iron deficient diet rarely showed effects of iron deficiency. One of the primary differences with the mice was that we were unable to obtain them at the very young age like we were able to do with the rats. This made it much more difficult to induce the iron deficiency necessary to answer our questions.
Overall, eleven undergraduate students were involved in these projects as well as two Master’s student. The funds were used to help offset costs associate with travel to present abstract presentations at the annual Experimental Biology meeting in 2012 and 2013. We also published a manuscript from the work we did in the Journal Nutrition and Metabolism. Funds were also used to purchase animals and supplies to facilitate a productive mentoring environment for work on this proposal. Undergraduate students mentored on this project include, Drew Smith, Isaac Torres, Michael Larson, Jordan Johnson, Brad Bohman, Tim Griffith, Will Wagner, Dustin Nygard, Elizabeth Brigham, and Squire Hepworth. Four of these students are currently attending medical school, one is attending Dental School, four are applying/interviewing for graduate programs and another is applying to PhD programs.
Abstracts directly associated with this proposal:
- Hardman SE, Merrill JF, Thomson DM, Hancock CR. The effect of iron deficiency on AMPK subunit isoform composition in skeletal muscle. FASEB J April 9, 2013 27:1202.22
- Merrill JF, Hepworth SD, Willie S, Winder WW, Thomson DM, and Hancock CR. Iron deficiency causes a shift in AMP-activated protein kinase (AMPK) catalytic subunit composition in rat skeletal muscle. FASEB J 26: 1144.1112, 2012.
Peer-reviewed manuscript from the work directly associated with this proposal:
- Merrill JF, Thomson DM, Hardman SE, Hepworth SD, Willie S, and Hancock CR. Iron deficiency causes a shift in AMP-activated protein kinase (AMPK) subunit composition in rat skeletal muscle. Nutr Metab (Lond) 9: 104, 2012.
(Two master’s students and two undergraduate students were co-authors of this manuscript).
- Cardon BR, Stallings MT, Brunson SE, Hart CM, Swiss MD, Hepworth SD, Christensen MJ, and Hancock CR. Dietary isoflavones and supplemental selenium show interactive effects on blood-glucose homeostasis in male FVB mice. FASEB J 26: 869.814, 2012.
- Stallings MT, Hardman JM, Hart CM, Christensen MJ, and Hancock CR. Fiber-type skeletal muscle response to dietary selenium and isoflavone supplementation in male mice. FASEB J 26: 1086.1025, 2012.
- Curtis M, Henriksen B, Fillmore N, Winder WW, Thomson DM, and Hancock CR. Chronic activation of AMPK limits hepatic triglyceride accumulation independent of changes in total glycerol-3-phosphate-acyltransferase activity. FASEB J 25: 1117.1110, 2011.
- Henriksen BS, Curtis ME, Fillmore N, Cardon BR, Thomson DM, Hancock CR. The effects of chronic and systemic AICAR treatment on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding. Diabetol Metab Syndr. May 31;5(1):29.2013.
In addition to these abstracts and the manuscript that came about from this proposal, the following abstracts were published on related projects that received support from a previous MEG grant. These abstracts and publication were not completed in time to be reported on the previous final reports. These abstracts were presented at Experimental Biology in 2012 and 2011. The manuscript was published in 2013. There were 12 undergraduate co-authorships on the abstracts and paper and two different graduate student (Masters) co-authors.