TRI Skeletal Muscle Adaptation(s): From the Field to the Lab and Clinic. Bite of Science Orlando

Transcription

1 Skeletal Muscle Adaptation(s): From the Field to the Lab and Clinic Bite of Science Orlando Robert Standley, PhD, ATC, CSCS 3/3/216

2 2 The Gameplan Skeletal Muscle and Exercise Research! Athletics/Rehabilitation, Aging, Metabolism To take you from the Field to the Lab and Clinic Highlight my path from the West Coast to East Coast

3 3 The Field

4 4 The Field Meets the Lab Effects of High Dose Fish Oil Supplementation on Delayed Onset Muscle Soreness (DOMS) and Inflammatory Markers Biodex

5 5 The Lab I I/IIa IIa IIa/IIx IIx I/IIa/IIx Slow Oxidative Fast Glycolytic Colin Jackson

6 6 NSAID Consumption Americans spend over 2.5 billion dollars on Over-the Counter NSAIDs per year Top two = Ibuprofen, Acetaminophen Heart and COX-2 Celebrex, Vioxx What happens to Skeletal muscle? Blunted normal response in protein synthesis in young men and women after resistance training

7 COX-Inhibitors and Skeletal Muscle Receptor Phospholipid PGF 2α Receptor PLA 2 Muscle Atrophy Arachadonic Acid COX PGH 2 COX-Inhibitors Muscle Growth Acute RE Drugs PGF 2α and FSR Synthase PGF 2α Synthase PGF 2α

8 Percent Kilograms TRI Aging Training Study Resistance Training Program 3 x 1 Knee Ext, 3d/wk 3mo Drug Consumption Acetaminophen (4,mg) Ibuprofen (1,2mg) Pre and Post Training Measurements Screening Muscle Size MRI Muscle Strength Biopsy Quadriceps Muscle Size Quadriceps Muscle Strength * * * Drugs Stimulate 25-5% 12 Increases in Muscle Mass and Strength Above 6 Placebo * * * Placebo Acetphen Ibuprofen Placebo Acetphen Ibuprofen Placebo Reversed: 7yr Sarcopenia Drug Groups Reversed: 1yr Sarcopenia * P<.5 from Pre-Training P<.5 from Placebo Trappe et al. 211

9 Mechanism Underlying Muscle Growth? 1. Identified and Measured 21 Components Associated with Muscle Growth: 7 Enzymes, 2 Receptors (PG) 3 Growth Regulators 4 Atrophy Regulators 5 Inflammatory Regulators Focus on 3 Components

10 Fold Change TRI Proposed Mechanism #1 Receptor 2 PGF 2α Receptor Phospholipid Pre Post PGF 2α Rec PGF 2α Rec PGF 2α Rec PLA 2 Muscle Atrophy 1 Arachadonic Acid Muscle Growth COX COX-Inhibitors Placebo Acetaminophen Ibuprofen PGH 2 Synthase PGF 2α Synthase PGF 2α

11 Fold Change Fold Change TRI Mechanism Underlying Muscle Growth? 3 * IL-6 Pre Post 2 * MuRF-1 Pre Post Placebo Acetphen Ibuprofen Placebo Acetphen Ibuprofen IL-6 Stimulates Net Skeletal Muscle Loss MuRF-1 is a E3 Ubiquitin Ligase that Contributes to Skeletal Muscle Proteolysis Trappe et al. 213 AJPReg

12 Proposed Mechanism of Action Drugs EP4 Not Known if this Occurs in Human NF-κB Skeletal Muscle IL-6 MuRF-1 Drugs Net Muscle Loss Proteolysis Drugs

13 Ex Vivo Study 1. Development of ex vivo Methodology 2. Ex vivo Study Design and Results

14 Ex Vivo Study

15 Fold Change from Control Fold Change from Control TRI Ex Vivo Study 4 IL-6 * 2 MuRF-1 * CON CON Confirm PGE Stimulates IL-6 and MuRF-1 Transcription in Human Skeletal Muscle * P<.5 Thus Blocking PGE Production with COX-Inhibitors during RE Reduces the Negative Effects of IL-6 and MuRF-1 on Muscle Growth

16 Fold Change Fold Change TRI Proposed Mechanism #2 3 Receptor * IL-6 Pre Post Phospholipid 2 PLA 2 MuRF-1 PGF 2α Receptor 2 1 NFκB Muscle Atrophy IL-6 MuRF-1 Arachadonic 1 Acid Muscle Growth COX COX-Inhibitors Muscle Atrophy Placebo Acetaminophen Ibuprofen PGH 2 Placebo Acetaminophen Ibuprofen Synthase PGF 2α Synthase PGF 2α

17 Kilograms Percent TRI NSAID Study Summary * Quadriceps Muscle Size * * * * * Placebo Acetaminophen Ibuprofen Quadriceps Muscle Strength Placebo Acetaminophen Ibuprofen PGF 2α receptor: an activator of skeletal muscle protein synthesis IL-6 and MuRF-1: mediators of skeletal muscle loss COX-inhibitor drug consumption produced an environment that: Promoted protein synthesis Reduced protein breakdown

18 18 Muscle Meets Metabolism

19 19 Peripheral Insulin Resistance Obesity/T2D Peripheral Insulin Resistance? Inactivity Caloric Excess Impaired Glucose Uptake Altered FA Metabolism Oxidative Stress

20 Abs Change GIR (mg/ffmkg/min) TRI 2 MIRAGE-Skeletal Muscle Lipid and Insulin Resistance and Aging 6 Month Intervention VO2max DEXA Muscle CSA-MRI Hyp-Eug Clamp MB X 2 Education Control (CON) Diet-Induced Weight Loss (DIWL) Diet-Induced Weight Loss+Exercise (WLEX) Hyp-Eug Clamp MB X 2 VO2max DEXA Muscle CSA-MRI CON DIWL WLEX

21 21 Take Home Message Questions and a Hypothesis Finding the answers Pubmed/Google Scholar Create your own solution Acquire the skills so you can answer Building a Building Creating Opportunities Who moved my cheese

22 22 Questions?