A systematic upregulation of nuclear and mitochondrial genes is not present in the initial post-exercise recovery period in human skeletal muscle

The purpose of the current investigation was to determine if an exercise-mediated upregulation of nuclear and mitochondrial-encoded genes targeted by the transcriptional co-activator peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC-1α) occurs in a systematic manner following different exercise intensities in humans. Ten recreationally active males (Age: 23 ±3 yrs; VO2peak: 41.8 ±6.6 mL/kg/min) completed two acute bouts of work-matched interval exercise at ~73% (LO) and ~100% (HI) of work rate at VO2peak in a randomized cross-over design. Muscle biopsies were taken before (Pre), immediately after (Post), and 3 hours into recovery (3hr) following each exercise bout. A main effect of time (pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Hindsight/RREB-1 functions in both the specification and differentiation of stem cells in the adult midgut of Drosophila

The adult Drosophila midgut is established during the larval/pupal transition from undifferentiated cells known as adult midgut precursors (AMPs). Four fundamental cell types are found in the adult midgut epithelium: undifferentiated intestinal stem cells (ISCs) and their committed daughter cells, enteroblasts (EBs), plus enterocytes (ECs) and enteroendocrine cells (EEs). Using the Drosophila posterior midgut as a model, we have studied the function of the transcription factor Hindsight (Hnt)/RREB-1 and its relationship to the Notch and Egfr signaling pathways. We show that hnt is required for EC differentiation in the context of ISC-to-EC differentiation, but not in the context of AMP-to-EC differentiation. In addition, we show that hnt is required for the establishment of viable or functional ISCs. Overall, our studies introduce hnt as a key factor in the regulation of both the developing and the mature adult midgut. We suggest that the nature of these contextual differences can be explained through the interaction of hnt with multiple signaling pathways

Acute upregulation of PGC-1α mRNA correlates with training-induced increases in SDH activity in human skeletal muscle

The purpose of the present study was to determine if acute responses in pgc-1α, vegfa, sdha, and gpd1/2 mRNA expression predict their associated chronic skeletal muscle molecular (SDH/GPD activity and substrate storage) and morphological (fibre type composition and capillary density) adaptations following training. Skeletal muscle biopsies were collected from fourteen recreationally active men (age: 22.0 ± 2.4 years) before (PRE) and 3 hours after (3HR) the completion of an acute bout of SIT (eight, 20-second intervals at ~170% VO2peak work rate separated by 10 seconds of recovery). Participants then completed 6 weeks of SIT 4 times per week with additional biopsies after 2 (MID) and 6 (POST) weeks of training. Acute increases in pgc-1α mRNA strongly predicted increases in SDH activity (a marker of oxidative capacity) from PRE and MID to POST (PRE-POST: r = 0.81, r2 = 0.65, pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG) of hypertensive rats had higher (p<0.05) caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05) ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05) Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05) Beclin-1 and ATG7 protein, as well as decreased (p<0.05) caspase-3, calpain, and cathepsin activity. Left ventricle (LV) of hypertensive rats had reduced (p<0.05) AMPKα and LC3II protein, as well as elevated (p<0.05) p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05) proteasome activity but reduced (p<0.05) caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats

alpha-Linolenic acid and exercise training independently, and additively, decrease blood pressure and prevent diastolic dysfunction in obese Zucker rats

Although α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4 week intervention, although the independent and combined effects of ALA and exercise reduced (P < 0.05) the serum free/esterified cholesterol ratio, only the ALA supplemented-exercise trained animals displayed a reduction in the content of both serum free and esterified cholesterol. Moreover, although ALA and endurance training individually increased cardiac output, stroke volume and end-diastolic volume, as well as reduced left ventricle fibrosis, mean blood pressure and total peripheral resistance, these responses were all greater following the combined intervention (ALA supplemented-exercise trained). These effects occurred independent of changes in oxidative phosphorylation proteins, markers of oxidative stress or endogenous anti-oxidant capacity. We propose that the beneficial effects of a combined intervention occur as a result of divergent mechanisms of action elicited by ALA and endurance exercise because only exercise training increased the capillary content in the left ventricle and skeletal muscle, and tended to decrease protein carbonylation in the left ventricle (P = 0.06). Taken together, our data indicate that combining ALA and endurance exercise provides additional improvements in cardiovascular disease risk reduction compared to singular interventions in the obese Zucker rat

Expression and phosphorylation status of AKT and AMPKα protein in muscle of sedentary and exercise-trained normotensive and hypertensive rats.

<p><i>A</i>: quantitative analysis and representative immunoblots of AKT and p-AKT (Thr³⁰⁸) protein in WG and LV (calculated p-AKT:AKT ratio is also shown). <i>B</i>: quantitative analysis and representative immunoblots of AMPKα and p-AMPKα (Thr¹⁷²) protein in WG and LV (calculated p-AMPKα:AMPKα ratio is also shown). Portions of Ponceau stained membranes are also shown to verify equal loading and quality of transfer. Values are means ± SEM (<i>n</i> = 8–12). ^† p<0.01 vs WKY (main effect); ^‡ p<0.005 vs WKY (main effect); ^§ p<0.001 vs WKY (main effect); * p<0.05 vs SED (main effect); ^∞ p<0.01 vs SED (main effect); ^# p<0.005 vs SED (main effect).</p

Autophagy-related mRNA expression in muscle of sedentary and exercise-trained normotensive and hypertensive rats.

<p><i>A</i>: quantitative analysis of LC3 mRNA in WG and LV. <i>B</i>: quantitative analysis of p62 mRNA in WG and LV. <i>C</i>: quantitative analysis of LAMP2 mRNA in WG and LV. Values are means ± SEM (<i>n</i> = 10–12). ^† p<0.05 vs WKY (main effect); * p<0.05 vs SED (main effect); ^¢ p<0.05 vs WKYSED (interaction effect); ^# p<0.005 vs WKYSED (interaction effect).</p

Ubiquitin-proteasome system (UPS)-related proteins and activity in muscle of sedentary and exercise-trained normotensive and hypertensive rats.

<p><i>A</i>: quantitative analysis and representative immunoblots of MuRF1 and MAFbx protein in WG and LV. Portions of Ponceau stained membranes are also shown to verify equal loading and quality of transfer. <i>B</i>: quantitative analysis of proteasome activity in the WG and LV. Values are means ± SEM (<i>n</i> = 9–12). ^† p<0.001 vs WKY (main effect); * p<0.05 vs SED (main effect); ^§ p<0.001 vs SED (main effect).</p