title: Preserved skeletal muscle protein anabolic response to acute exercise and protein intake in well-treated rheumatoid arthritis patients.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is often associated with diminished muscle mass, reflecting an imbalance between protein synthesis and protein breakdown. To investigate the anabolic potential of both exercise and nutritional protein intake we investigated the muscle protein synthesis rate and anabolic signaling response in patients with RA compared to healthy controls.
  
  
  METHODS
  Thirteen RA patients (age range 34-84 years; diagnosed for 1-32 years, median 8 years) were individually matched with 13 healthy controls for gender, age, BMI and activity level (CON). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay (ELISA) in resting blood samples obtained on two separate days. Skeletal muscle myofibrillar and connective tissue protein fractional synthesis rate (FSR) was measured by incorporation of the amino acid (13)C6-phenylalanine tracer in the overnight fasted state for 3 hours (BASAL) and 3 hours after intake of whey protein (0.5 g/kg lean body mass) alone (PROT, 3 hrs) and in combination with knee-extensor exercise (EX) with one leg (8 × 10 reps at 70 % of 1RM; PROT + EX, 3 hrs). Expression of genes related to inflammatory signaling, myogenesis and muscle growth/atrophy were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  CRP was significantly higher in the RA patients (2.25 (0.50) mg/l) than in controls (1.07 (0.25) mg/l; p = 0.038) and so was TNF-α (RA 1.18 (0.30) pg/ml vs. CON 0.64 (0.07) pg/ml; p = 0.008). Muscle myofibrillar protein synthesis in both RA patients and CON increased in response to PROT and PROT + EX, and even more with PROT + EX (p < 0.001), with no difference between groups (p > 0.05). The gene expression response was largely similar in RA vs. CON, however, expression of the genes coding for TNF-α, myogenin and HGF1 were more responsive to exercise in RA patients than in CON.
  
  
  CONCLUSIONS
  The study demonstrates that muscle protein synthesis rate and muscle gene expression can be stimulated by protein intake alone and in combination with physical exercise in patients with well-treated RA to a similar extent as in healthy individuals. This indicates that moderately inflamed RA patients have maintained their muscle anabolic responsiveness to physical activity and protein intake.
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. ullaramer@hotmail.com.|Section for Sports Science, Institute of Public Health, Aarhus University, Dalgas Avenue 4, 8000, Aarhus C, Denmark. ullaramer@hotmail.com.
authors.forename: Ulla Ramer
authors.initials: UR
authors.lastname: Mikkelsen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. kasperjuel@hotmail.com.
authors.forename: Kasper
authors.initials: K
authors.lastname: Dideriksen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. aaba@aarhus-akademi.dk.
authors.forename: Mads Bisgaard
authors.initials: MB
authors.lastname: Andersen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. boesenanders@hotmail.com.
authors.forename: Anders
authors.initials: A
authors.lastname: Boesen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. nikolajmoelkjaer@gmail.com.
authors.forename: Nikolai Mølkjær
authors.initials: NM
authors.lastname: Malmgaard-Clausen
authors.affiliation: Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Nordre Ringvej 57, 2600, Glostrup, Denmark. Inge.Juul.Soerensen@regionh.dk.
authors.forename: Inge Juul
authors.initials: IJ
authors.lastname: Sørensen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. peter@mrna.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. michaelkjaer@sund.ku.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Kjær
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital bldg 8, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. larsh@sund.ku.dk.|Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. larsh@sund.ku.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Holm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004032:Diet; D004044:Dietary Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D018501:Antirheumatic Agents; D004044:Dietary Proteins; D009124:Muscle Proteins