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Moderate Resistance Exercise Improves the Metabolic Profile of Adipose Tissue in a Model of Disuse Johan E. Harris 1, Lisa A. Baer 1, 2, Devin Sindeldecker 1, 3, Charles E. Wade 2, Kristin I. Stanford 1 1 Dorothy M. Davis Heart and Lung Research Institute; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210 2 Center for Translational Injury Research, University of Texas Health Science Center, Houston, TX 77030 3 Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210 Effects of Disuse and Exercise on Body Composition, cont. Introduction Ø Treatment of trauma and several other maladies requires patient immobilization and restriction of physical activity, which can result in impaired metabolic health. Ø In contrast to physical immobilization, physical activity and exercise improves metabolic health. Ø Both pg. WAT and sc. WAT mass are significantly decreased as a result of exercise in the ambulatory group (ANE vs. AE; P<0. 01). Ø There is also an overall effect of HU reducing both pg. WAT and sc. WAT mass when compared to the ANE rats (ANE vs. HUNE and HUE; P<0. 01) A marked decrease in adipocyte size was observed in both pg. WAT (Figure 3 A-E) and sc. WAT (Figure 4 A-E) in the combined model of disuse and resistance exercise. ANE Objective AE sc. WAT Gene expression for fatty acid metabolism & mitochondrial activity was restored in the HUE group sc. WAT Ø Ø HUNE HUE To determine if moderate resistance exercise can negate the effects of disuse on the metabolic profile of white adipose tissue (WAT). Ø Ø Ø Ø Four groups: Ambulatory No Exercise (ANE), Ambulatory Exercise (AE), Hind limb Unloaded No Exercise (HUNE), Hind limb Unloaded Exercise (HUE) Resistance exercise was initiated 10 -days prior to being randomized into assigned groups. Resistance exercise was achieved using a rodent ladder climbing model. A percentage of the rat’s body mass was calculated and this weight was added to the base of the tail during each climb. Tail weight was increased depending on climbing performance during each session. No rat was excluded from the study due to climbing performance. Disuse by HLU was initiated on day 1 of experiment. The experimental period was for 14 days, at which plasma and tissue samples were collected for future analysis. Adipocyte Size (mm 2) Exercise Protocol After 14 days, circulating FFAs were significantly reduced as a result of both hind limb unloading and resistance exercise (ANE vs. AE, HUNE, and HUE). Exercise significantly increased Cd 36, and Pgc 1 a expression in the ambulatory sc. WAT (ANE vs. AE; P<0. 05). HUNE rats had a significant decrease in Cd 36, and Pgc 1 a expression (ANE vs. HUNE; P<0. 05, P<0. 01). Exercise in the HU rats restored Cd 36, and Pgc 1 a expression to that of the ANE rats (HUNE vs. HUE; P<0. 05). Ldha expression was significantly decreased in HUNE rats (ANE and AE vs. HUNE; P<0. 05) but, exercise in the presence of disuse restored Ldha expression in sc. WAT to that of the ambulatory rats (HUNE vs. HUE; P<0. 05). ANE AE pg. WAT HUNE HUE Hindlimb unloading system allows for full cage access. Ø Resistance exercise significantly decreased body mass in the ambulatory rats (AE vs. ANE; P<0. 001). HUNE rats had a significantly decreased body mass compared to ANE rats (ANE vs. HUNE and HUE; P<0. 001). Ø In the HU groups, however, resistance exercise did not result in a further decrease in body mass than compared to the effect of the HU alone (HUE vs. HUNE). Ø White adipose tissue (WAT) mass was significantly reduced with exercise in the ambulatory group (ANE vs. AE; P<0. 01), and in both HU groups compared to the ANE group (ANE vs. HUNE and HUE; P<0. 01). Adipocyte Size (mm 2) Effects of Disuse and Exercise on Body Composition Ø Total muscle weight was significantly reduced in both HU groups when compared to both ambulatory groups (AE and ANE vs. HUE and HUNE; P<0. 01). Ø The soleus muscle also had a significant reduction in mass in the HU rats vs. the ambulatory rats. However, exercise significantly increased soleus mass in the HUE vs. HUNE group (P<0. 01) (Figure 1 D) when normalized for total body weight. Ø Ø Summary & Conclusions Soleus muscle mass loss is partially attenuated by resistance exercise in a model of disuse. Both sc. WAT and pg. WAT mass are reduced by exercise in ambulatory rats, and reduced in HU rats compared to ANE rats. Gene expression was significantly decreased in HU animals, but restored in the HUE rats for CD 36, Pgc 1 a, and Ldha, indicating restored metabolic activity after resistance exercise. Resistance exercise could be a novel therapeutic method for human bed rest patients to restore the lost metabolic health caused by the disuse experienced on bed rest.