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Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

ABSTRACT: Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair.Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression.We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1? (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1? (0.74 fold change; p < 0.05); while vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat stress repressed PGC-1? (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05).These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.

SUBMITTER: Petrie MA

PROVIDER: S-EPMC4972309 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

Petrie Michael A MA Kimball Amy L AL McHenry Colleen L CL Suneja Manish M Yen Chu-Ling CL Sharma Arpit A Shields Richard K RK

PloS one 20160803 8

<h4>Unlabelled</h4>Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.<h4>Purpose</h4>The purpose ...[more]

PMID: 27486743

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Project description:The quality and strength of the skeleton is regulated by mechanical loading and adequate mineral intake of calcium (Ca) and phosphorus (P). Whole body vibration (WBV) has been shown to elicit adaptive responses in the skeleton, such as increased bone mass and strength. This experiment was designed to determine the effects of WBV and dietary Ca and P on bone microarchitecture and turnover. A total of 26 growing pigs were utilized in a 60-d experiment. Pigs were randomly assigned within group to a 2 × 2 factorial design with dietary Ca and P concentration (low and adequate) as well as WBV. The adequate diet was formulated to meet all nutritional needs according to the NRC recommendations for growing pigs. Low Ca, P diets had 0.16% lower Ca and 0.13% lower P than the adequate diet. Pigs receiving WBV were vibrated 30 min/d, 3 d/wk at a magnitude of 1 to 2 mm and a frequency of 50 Hz. On days 0, 30, and 60, digital radiographs were taken to determine bone mineral content by radiographic bone aluminum equivalency (RBAE) and serum was collected to measure biochemical markers of bone formation (osteocalcin, OC) and bone resorption (carboxy-terminal collagen crosslinks, CTX-I). At day 60, pigs were euthanized and the left third metacarpal bone was excised for detailed analysis by microcomputed tomography (microCT) to measure trabecular microarchitecture and cortical bone geometry. Maximum RBAE values for the medial or lateral cortices were not affected (P > 0.05) by WBV. Pigs fed adequate Ca and P tended (P = 0.10) to have increased RBAE max values for the medial and lateral cortices. WBV pigs had significantly decreased serum CTX-1 concentrations (P = 0.044), whereas animals fed a low Ca and P diet had increased (P < 0.05) OC concentrations. In bone, WBV pigs showed a significantly lower trabecular number (P = 0.002) and increased trabecular separation (P = 0.003), whereas cortical bone parameters were not significantly altered by WBV or diet (P > 0.05). In summary, this study confirmed the normal physiological responses of the skeleton to a low Ca, P diet. Interestingly, although the WBV protocol utilized in this study did not elicit any significant osteogenic response, decreases in CTX-1 in response to WBV may have been an early local adaptive bone response. We interpret these data to suggest that the frequency and amplitude of WBV was likely sufficient to elicit a bone remodeling response, but the duration of the study may not have captured the full extent of an entire bone remodeling cycle.

Project description:AimHeat exposure has been indicated to positively affect glucose metabolism. An involvement of heat shock protein 72 (HSP72) in the enhancement of insulin sensitivity upon heat exposure has been previously suggested. Here, we performed an intervention study exploring the effect of passive heat acclimation (PHA) on glucose metabolism and intracellular (a) HSP72 concentrations in overweight humans.MethodsEleven non-diabetic overweight (BMI 27-35 kg/m2 ) participants underwent 10 consecutive days of PHA (4-6 h/day, 34.4 ± 0.2°C, 22.8 ± 2.7%RH). Before and after PHA, whole-body insulin sensitivity was assessed using a one-step hyperinsulinaemic-euglycaemic clamp, skeletal muscle biopsies were taken to measure intracellular iHSP72, energy expenditure and substrate oxidation were measured using indirect calorimetry and blood samples were drawn to assess markers of metabolic health. Thermophysiological adaptations were measured during a temperature ramp protocol before and after PHA.ResultsDespite a lack of change in iHSP72, 10 days of PHA reduced basal (9.7 ± 1.4 pre- vs 8.4 ± 2.1 μmol · kg-1 · min-1 post-PHA, P = .038) and insulin-stimulated (2.1 ± 0.9 pre- vs 1.5 ± 0.8 μmol · kg-1 · min-1 post-PHA, P = .005) endogenous glucose production (EGP) and increased insulin suppression of EGP (78.5 ± 9.7% pre- vs 83.0 ± 7.9% post-PHA, P = .028). Consistently, fasting plasma glucose (6.0 ± 0.5 pre- vs 5.8 ± 0.4 mmol/L post-PHA, P = .013) and insulin concentrations (97 ± 55 pre- vs 84 ± 49 pmol/L post-PHA, P = .026) decreased significantly. Moreover, fat oxidation increased, and free fatty acids as well as cholesterol concentrations and mean arterial pressure decreased after PHA.ConclusionOur results show that PHA for 10 days improves glucose metabolism and enhances fat metabolism, without changes in iHSP72. Further exploration of the therapeutic role of heat in cardio-metabolic disorders should be considered.

Dataset Information

Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

Publications

Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

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