Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation (Columbus) (Columbus)
Primary Purpose
Obesity, Disorder of Lipid Storage and Metabolism, Lipid Metabolism Disorders
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise
Sponsored by
About this trial
This is an interventional basic science trial for Obesity focused on measuring skeletal muscle, adipose tissue, metabolism, oxidation, mitochondrial capacity
Eligibility Criteria
Inclusion Criteria:
Applicable to all Groups
- Healthy men and women, aged 18 - 40, inclusive.
- Willing to stop alcohol and caffeine consumption for 48 hours preceding each blood draw
Applicable to Group 1
- BMI between 22 and 29.9 kg/m2
- Not involved in regular exercise program
- Willing to exercise every day for the study period
Applicable to Group 2
- BMI between 22 and 29.9 kg/m2
Maximal oxygen uptake (VO2max) ≥ 45 ml/kg fat-free mass
/min
- Engaged in a minimum of 1.5 h of moderate to vigorous intensity aerobic exercise 3 times/ week
Applicable to Group 3
- BMI ≥ 30 kg/m2 and weight ≤ 350 lbs
- Not involved in a regular exercise program
Exclusion Criteria:
Applicable to All Groups
- History of Type 2 Diabetes
- "Unfavorable anatomy" for continuous venous blood sample collection
- Abnormal resting ECG
- Significant renal, cardiac, liver, lung, or neurological disease (controlled hypertension is acceptable if baseline bp < 140/90 on medications)
- Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
- Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
- New onset (<3 months on a stable regime) use of oral contraceptives or hormone replacement therapy
- Alcohol or other drug abuse
- Smoking within the past 3 months
- Females that are currently or have been pregnant or are currently or have nursed a child within the last 12 months (minimum).
- Parental enrollment into the study that compromises the well being of the child [no partner or connected caregiver]
- Unwilling or unable to abstain from caffeine or alcohol 48 hours prior to metabolic rate measurements
- Increased liver function tests
- Metal objects that would interfere with the measurement of body composition /magnetic resonance spectroscopy such as implanted rods, surgical clips, etc
- Any New York Heart Association class of congestive heart failure
- History of deep vein thrombosis or pulmonary embolism
- Significant varicose veins
- Abnormal blood count/Anemia, or blood donation within the last 2 months
- Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
- Bariatric surgery or liposuction within the previous 3 years
- Cancer (active malignancy with or without concurrent chemotherapy)
- Rheumatoid disease
- Bypass graft in limb
- Known genetic factor (Factor V Leiden, etc) or hypercoagulable state
- Diagnosed peripheral arterial or vascular disease, or intermittent claudication
- Family history of primary deep vein thrombosis or pulmonary embolism
- Peripheral neuropathy
- Claustrophobia
- Frequent nocturnal urination and/or sleep apnea
- Presence of any condition that, in the opinion of the investigator, compromises participant safety or data integrity or the participants' ability to complete the training protocol
Applicable to Group 2
- Gait problems
- Major Depression
- Presence of an eating disorder or eating attitudes/behaviors that could interfere with the study completion
- Unwilling or unable to complete the protocol
Applicable to Group 3
- HbA1c ≥ 6.5% (O)
Sites / Locations
- Translational Research Institute for Metabolism and Diabetes
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
No Intervention
No Intervention
Arm Label
Group 1 - Regular exercise
Group 2 - Athlete exercise
Group 3 - Obese No Exercise
Arm Description
Alternate interval training and aerobic training and exercise
Athletes are not given any intervention
The Obese group will not receive intervention
Outcomes
Primary Outcome Measures
Measure change in mitochondrial capacity
The difference will be measured in obese, lean and athletic participants.
The Phosphocreatine (PCr) recovery time constant and the PCr level in oxygenated muscle at rest will be used to calculate maximum mitochondrial capacity.
Secondary Outcome Measures
Measure change of expression of proteins
The difference will be measured in obese, lean and athletic participants.
This will be taken from muscle biopsy and/or blood plasma samples obtained at baseline, before and after exercise.
Measure change in mRNA/miRNA levels
The difference will be measured in obese, lean and athletic participants.
This will be taken from muscle biopsy and/or blood plasma samples obtained at baseline, before and after exercise.
Full Information
NCT ID
NCT01911091
First Posted
July 24, 2013
Last Updated
June 6, 2023
Sponsor
AdventHealth Translational Research Institute
Collaborators
Sanford-Burnham Medical Research Institute, Takeda
1. Study Identification
Unique Protocol Identification Number
NCT01911091
Brief Title
Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation (Columbus)
Acronym
Columbus
Official Title
Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation in Both Skeletal Muscle and Adipose Tissue
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AdventHealth Translational Research Institute
Collaborators
Sanford-Burnham Medical Research Institute, Takeda
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to collect data to help researchers identify factors, such as certain proteins or genetic codes, that are secreted from muscle that are associated with the beneficial effects of exercise.
Detailed Description
Study Objectives:
To identify specific changes in messenger ribonucleic acid (mRNA)/micro ribonucleic acid (miRNA) expression in muscle associated with higher or lower relative measures of mitochondrial capacity and fat oxidation.
To identify secreted factors/miRNAs that specifically relate to the metabolic response of muscle and that are present after a single initial bout of exercise.
To collect the appropriate clinical samples (muscle and adipose tissue, plasma/serum) to enable validation of myokines associated with changes in oxygen consumption/mitochondrial content via in vivo and in vitro discovery efforts.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Disorder of Lipid Storage and Metabolism, Lipid Metabolism Disorders, Metabolic Disorder
Keywords
skeletal muscle, adipose tissue, metabolism, oxidation, mitochondrial capacity
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group 1 - Regular exercise
Arm Type
Experimental
Arm Description
Alternate interval training and aerobic training and exercise
Arm Title
Group 2 - Athlete exercise
Arm Type
No Intervention
Arm Description
Athletes are not given any intervention
Arm Title
Group 3 - Obese No Exercise
Arm Type
No Intervention
Arm Description
The Obese group will not receive intervention
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Intervention Description
A 5-minute warm-up and a 5-minute cool-down prior to and following each exercise session, respectively. There will be alternating days of interval training and aerobic training. The interval training will be performed on an upright stationary bike, while the aerobic training will be performed on a treadmill. The interval training will consist of five-minute bouts of higher intensity alternated with 4 minutes of lower intensity for a total duration of 45 minutes. Intensity will increase each week. The aerobic training component will be fixed at a moderate intensity, but will increase in duration each week from 45 minutes to 75 minutes to 90 minutes during the third and final week.
Primary Outcome Measure Information:
Title
Measure change in mitochondrial capacity
Description
The difference will be measured in obese, lean and athletic participants.
The Phosphocreatine (PCr) recovery time constant and the PCr level in oxygenated muscle at rest will be used to calculate maximum mitochondrial capacity.
Time Frame
Baseline (Day -6), Day 18
Secondary Outcome Measure Information:
Title
Measure change of expression of proteins
Description
The difference will be measured in obese, lean and athletic participants.
This will be taken from muscle biopsy and/or blood plasma samples obtained at baseline, before and after exercise.
Time Frame
Baseline (Day -6), Day 0, Day 5, Day 12, Day 18
Title
Measure change in mRNA/miRNA levels
Description
The difference will be measured in obese, lean and athletic participants.
This will be taken from muscle biopsy and/or blood plasma samples obtained at baseline, before and after exercise.
Time Frame
Baseline (Day -6), Day 0, Day 5, Day 12, Day 18
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Applicable to all Groups
Healthy men and women, aged 18 - 40, inclusive.
Willing to stop alcohol and caffeine consumption for 48 hours preceding each blood draw
Applicable to Group 1
BMI between 22 and 29.9 kg/m2
Not involved in regular exercise program
Willing to exercise every day for the study period
Applicable to Group 2
BMI between 22 and 29.9 kg/m2
Maximal oxygen uptake (VO2max) ≥ 45 ml/kg fat-free mass
/min
Engaged in a minimum of 1.5 h of moderate to vigorous intensity aerobic exercise 3 times/ week
Applicable to Group 3
BMI ≥ 30 kg/m2 and weight ≤ 350 lbs
Not involved in a regular exercise program
Exclusion Criteria:
Applicable to All Groups
History of Type 2 Diabetes
"Unfavorable anatomy" for continuous venous blood sample collection
Abnormal resting ECG
Significant renal, cardiac, liver, lung, or neurological disease (controlled hypertension is acceptable if baseline bp < 140/90 on medications)
Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
New onset (<3 months on a stable regime) use of oral contraceptives or hormone replacement therapy
Alcohol or other drug abuse
Smoking within the past 3 months
Females that are currently or have been pregnant or are currently or have nursed a child within the last 12 months (minimum).
Parental enrollment into the study that compromises the well being of the child [no partner or connected caregiver]
Unwilling or unable to abstain from caffeine or alcohol 48 hours prior to metabolic rate measurements
Increased liver function tests
Metal objects that would interfere with the measurement of body composition /magnetic resonance spectroscopy such as implanted rods, surgical clips, etc
Any New York Heart Association class of congestive heart failure
History of deep vein thrombosis or pulmonary embolism
Significant varicose veins
Abnormal blood count/Anemia, or blood donation within the last 2 months
Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
Bariatric surgery or liposuction within the previous 3 years
Cancer (active malignancy with or without concurrent chemotherapy)
Rheumatoid disease
Bypass graft in limb
Known genetic factor (Factor V Leiden, etc) or hypercoagulable state
Diagnosed peripheral arterial or vascular disease, or intermittent claudication
Family history of primary deep vein thrombosis or pulmonary embolism
Peripheral neuropathy
Claustrophobia
Frequent nocturnal urination and/or sleep apnea
Presence of any condition that, in the opinion of the investigator, compromises participant safety or data integrity or the participants' ability to complete the training protocol
Applicable to Group 2
Gait problems
Major Depression
Presence of an eating disorder or eating attitudes/behaviors that could interfere with the study completion
Unwilling or unable to complete the protocol
Applicable to Group 3
HbA1c ≥ 6.5% (O)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven R Smith, MD
Organizational Affiliation
Translational Research Institute for Metabolism and Diabetes
Official's Role
Principal Investigator
Facility Information:
Facility Name
Translational Research Institute for Metabolism and Diabetes
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11333990
Citation
Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.
Results Reference
background
PubMed Identifier
18525377
Citation
Nocon M, Hiemann T, Muller-Riemenschneider F, Thalau F, Roll S, Willich SN. Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil. 2008 Jun;15(3):239-46. doi: 10.1097/HJR.0b013e3282f55e09.
Results Reference
background
PubMed Identifier
22473333
Citation
Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012 Apr 3;8(8):457-65. doi: 10.1038/nrendo.2012.49.
Results Reference
background
PubMed Identifier
18923185
Citation
Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008 Oct;88(4):1379-406. doi: 10.1152/physrev.90100.2007.
Results Reference
background
PubMed Identifier
17331593
Citation
Pedersen BK, Fischer CP. Beneficial health effects of exercise--the role of IL-6 as a myokine. Trends Pharmacol Sci. 2007 Apr;28(4):152-6. doi: 10.1016/j.tips.2007.02.002. Epub 2007 Feb 28.
Results Reference
background
PubMed Identifier
14609022
Citation
Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Febbraio M, Saltin B. Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil. 2003;24(2-3):113-9. doi: 10.1023/a:1026070911202.
Results Reference
background
PubMed Identifier
11320633
Citation
MacIntyre DL, Sorichter S, Mair J, Berg A, McKenzie DC. Markers of inflammation and myofibrillar proteins following eccentric exercise in humans. Eur J Appl Physiol. 2001 Mar;84(3):180-6. doi: 10.1007/s004210170002.
Results Reference
background
PubMed Identifier
18059606
Citation
Nielsen AR, Pedersen BK. The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15. Appl Physiol Nutr Metab. 2007 Oct;32(5):833-9. doi: 10.1139/H07-054.
Results Reference
background
PubMed Identifier
19387610
Citation
Matthews VB, Astrom MB, Chan MH, Bruce CR, Krabbe KS, Prelovsek O, Akerstrom T, Yfanti C, Broholm C, Mortensen OH, Penkowa M, Hojman P, Zankari A, Watt MJ, Bruunsgaard H, Pedersen BK, Febbraio MA. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia. 2009 Jul;52(7):1409-18. doi: 10.1007/s00125-009-1364-1. Epub 2009 Apr 22. Erratum In: Diabetologia. 2012 Mar;55(3):864. Diabetologia. 2015 Apr;58(4):854-5.
Results Reference
background
PubMed Identifier
17151862
Citation
Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, Fischer CP, Lindegaard B, Petersen AM, Taudorf S, Secher NH, Pilegaard H, Bruunsgaard H, Pedersen BK. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007 Feb;50(2):431-8. doi: 10.1007/s00125-006-0537-4. Epub 2006 Dec 7.
Results Reference
background
PubMed Identifier
18460341
Citation
Arner P, Pettersson A, Mitchell PJ, Dunbar JD, Kharitonenkov A, Ryden M. FGF21 attenuates lipolysis in human adipocytes - a possible link to improved insulin sensitivity. FEBS Lett. 2008 May 28;582(12):1725-30. doi: 10.1016/j.febslet.2008.04.038. Epub 2008 May 5.
Results Reference
background
PubMed Identifier
17550778
Citation
Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007 Jun;5(6):426-37. doi: 10.1016/j.cmet.2007.05.002.
Results Reference
background
PubMed Identifier
18687777
Citation
Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, Moller DE, Kharitonenkov A. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology. 2008 Dec;149(12):6018-27. doi: 10.1210/en.2008-0816. Epub 2008 Aug 7.
Results Reference
background
PubMed Identifier
17550777
Citation
Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, Li Y, Goetz R, Mohammadi M, Esser V, Elmquist JK, Gerard RD, Burgess SC, Hammer RE, Mangelsdorf DJ, Kliewer SA. Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab. 2007 Jun;5(6):415-25. doi: 10.1016/j.cmet.2007.05.003.
Results Reference
background
PubMed Identifier
15902306
Citation
Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005 Jun;115(6):1627-35. doi: 10.1172/JCI23606. Epub 2005 May 2.
Results Reference
background
PubMed Identifier
17068132
Citation
Kharitonenkov A, Wroblewski VJ, Koester A, Chen YF, Clutinger CK, Tigno XT, Hansen BC, Shanafelt AB, Etgen GJ. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology. 2007 Feb;148(2):774-81. doi: 10.1210/en.2006-1168. Epub 2006 Oct 26.
Results Reference
background
PubMed Identifier
17601491
Citation
Lundasen T, Hunt MC, Nilsson LM, Sanyal S, Angelin B, Alexson SE, Rudling M. PPARalpha is a key regulator of hepatic FGF21. Biochem Biophys Res Commun. 2007 Aug 24;360(2):437-40. doi: 10.1016/j.bbrc.2007.06.068. Epub 2007 Jun 21.
Results Reference
background
PubMed Identifier
16936195
Citation
Wente W, Efanov AM, Brenner M, Kharitonenkov A, Koster A, Sandusky GE, Sewing S, Treinies I, Zitzer H, Gromada J. Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes. 2006 Sep;55(9):2470-8. doi: 10.2337/db05-1435.
Results Reference
background
PubMed Identifier
21309058
Citation
Mashili FL, Austin RL, Deshmukh AS, Fritz T, Caidahl K, Bergdahl K, Zierath JR, Chibalin AV, Moller DE, Kharitonenkov A, Krook A. Direct effects of FGF21 on glucose uptake in human skeletal muscle: implications for type 2 diabetes and obesity. Diabetes Metab Res Rev. 2011 Mar;27(3):286-97. doi: 10.1002/dmrr.1177.
Results Reference
background
PubMed Identifier
22398021
Citation
Lee MS, Choi SE, Ha ES, An SY, Kim TH, Han SJ, Kim HJ, Kim DJ, Kang Y, Lee KW. Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-kappaB. Metabolism. 2012 Aug;61(8):1142-51. doi: 10.1016/j.metabol.2012.01.012. Epub 2012 Mar 6.
Results Reference
background
PubMed Identifier
22237023
Citation
Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012 Jan 11;481(7382):463-8. doi: 10.1038/nature10777.
Results Reference
background
PubMed Identifier
2035628
Citation
Goodman MN. Tumor necrosis factor induces skeletal muscle protein breakdown in rats. Am J Physiol. 1991 May;260(5 Pt 1):E727-30. doi: 10.1152/ajpendo.1991.260.5.E727.
Results Reference
background
PubMed Identifier
15746179
Citation
Li YP, Chen Y, John J, Moylan J, Jin B, Mann DL, Reid MB. TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J. 2005 Mar;19(3):362-70. doi: 10.1096/fj.04-2364com.
Results Reference
background
PubMed Identifier
15701678
Citation
Williamson DL, Kimball SR, Jefferson LS. Acute treatment with TNF-alpha attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism. Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E95-104. doi: 10.1152/ajpendo.00397.2004. Epub 2005 Feb 8.
Results Reference
background
PubMed Identifier
16967774
Citation
Nieman DC, Henson DA, Gojanovich G, Davis JM, Murphy EA, Mayer EP, Pearce S, Dumke CL, Utter AC, McAnulty SR, McAnulty LS. Influence of carbohydrate on immune function following 2 h cycling. Res Sports Med. 2006 Jul-Sep;14(3):225-37. doi: 10.1080/15438620600854793.
Results Reference
background
PubMed Identifier
12533503
Citation
Nieman DC, Davis JM, Henson DA, Walberg-Rankin J, Shute M, Dumke CL, Utter AC, Vinci DM, Carson JA, Brown A, Lee WJ, McAnulty SR, McAnulty LS. Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run. J Appl Physiol (1985). 2003 May;94(5):1917-25. doi: 10.1152/japplphysiol.01130.2002. Epub 2003 Jan 17.
Results Reference
background
PubMed Identifier
10976104
Citation
Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, Kambadur R. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J Biol Chem. 2000 Dec 22;275(51):40235-43. doi: 10.1074/jbc.M004356200.
Results Reference
background
PubMed Identifier
9139826
Citation
McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997 May 1;387(6628):83-90. doi: 10.1038/387083a0.
Results Reference
background
PubMed Identifier
11877467
Citation
McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest. 2002 Mar;109(5):595-601. doi: 10.1172/JCI13562.
Results Reference
background
PubMed Identifier
19509018
Citation
Tu P, Bhasin S, Hruz PW, Herbst KL, Castellani LW, Hua N, Hamilton JA, Guo W. Genetic disruption of myostatin reduces the development of proatherogenic dyslipidemia and atherogenic lesions in Ldlr null mice. Diabetes. 2009 Aug;58(8):1739-48. doi: 10.2337/db09-0349. Epub 2009 Jun 9.
Results Reference
background
PubMed Identifier
12181291
Citation
Zoll J, Sanchez H, N'Guessan B, Ribera F, Lampert E, Bigard X, Serrurier B, Fortin D, Geny B, Veksler V, Ventura-Clapier R, Mettauer B. Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle. J Physiol. 2002 Aug 15;543(Pt 1):191-200. doi: 10.1113/jphysiol.2002.019661.
Results Reference
background
PubMed Identifier
1573181
Citation
Coggan AR, Spina RJ, King DS, Rogers MA, Brown M, Nemeth PM, Holloszy JO. Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. J Gerontol. 1992 May;47(3):B71-6. doi: 10.1093/geronj/47.3.b71.
Results Reference
background
PubMed Identifier
7665396
Citation
Proctor DN, Sinning WE, Walro JM, Sieck GC, Lemon PW. Oxidative capacity of human muscle fiber types: effects of age and training status. J Appl Physiol (1985). 1995 Jun;78(6):2033-8. doi: 10.1152/jappl.1995.78.6.2033.
Results Reference
background
PubMed Identifier
4797912
Citation
Hoppeler H, Luthi P, Claassen H, Weibel ER, Howald H. The ultrastructure of the normal human skeletal muscle. A morphometric analysis on untrained men, women and well-trained orienteers. Pflugers Arch. 1973 Nov 28;344(3):217-32. doi: 10.1007/BF00588462. No abstract available.
Results Reference
background
PubMed Identifier
17095651
Citation
Tarnopolsky MA, Rennie CD, Robertshaw HA, Fedak-Tarnopolsky SN, Devries MC, Hamadeh MJ. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am J Physiol Regul Integr Comp Physiol. 2007 Mar;292(3):R1271-8. doi: 10.1152/ajpregu.00472.2006. Epub 2006 Nov 9.
Results Reference
background
PubMed Identifier
19556459
Citation
Larsen RG, Callahan DM, Foulis SA, Kent-Braun JA. In vivo oxidative capacity varies with muscle and training status in young adults. J Appl Physiol (1985). 2009 Sep;107(3):873-9. doi: 10.1152/japplphysiol.00260.2009. Epub 2009 Jun 25.
Results Reference
background
PubMed Identifier
11583863
Citation
Mettauer B, Zoll J, Sanchez H, Lampert E, Ribera F, Veksler V, Bigard X, Mateo P, Epailly E, Lonsdorfer J, Ventura-Clapier R. Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active control subjects. J Am Coll Cardiol. 2001 Oct;38(4):947-54. doi: 10.1016/s0735-1097(01)01460-7.
Results Reference
background
PubMed Identifier
23150693
Citation
Conley KE, Amara CE, Bajpeyi S, Costford SR, Murray K, Jubrias SA, Arakaki L, Marcinek DJ, Smith SR. Higher mitochondrial respiration and uncoupling with reduced electron transport chain content in vivo in muscle of sedentary versus active subjects. J Clin Endocrinol Metab. 2013 Jan;98(1):129-36. doi: 10.1210/jc.2012-2967. Epub 2012 Nov 12.
Results Reference
background
PubMed Identifier
16204368
Citation
Bogacka I, Ukropcova B, McNeil M, Gimble JM, Smith SR. Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro. J Clin Endocrinol Metab. 2005 Dec;90(12):6650-6. doi: 10.1210/jc.2005-1024. Epub 2005 Oct 4.
Results Reference
background
PubMed Identifier
21760887
Citation
Sparks LM, Moro C, Ukropcova B, Bajpeyi S, Civitarese AE, Hulver MW, Thoresen GH, Rustan AC, Smith SR. Remodeling lipid metabolism and improving insulin responsiveness in human primary myotubes. PLoS One. 2011;6(7):e21068. doi: 10.1371/journal.pone.0021068. Epub 2011 Jul 8.
Results Reference
background
PubMed Identifier
20631206
Citation
Henningsen J, Rigbolt KT, Blagoev B, Pedersen BK, Kratchmarova I. Dynamics of the skeletal muscle secretome during myoblast differentiation. Mol Cell Proteomics. 2010 Nov;9(11):2482-96. doi: 10.1074/mcp.M110.002113. Epub 2010 Jul 14.
Results Reference
background
PubMed Identifier
20603081
Citation
Zhang Y, Liu D, Chen X, Li J, Li L, Bian Z, Sun F, Lu J, Yin Y, Cai X, Sun Q, Wang K, Ba Y, Wang Q, Wang D, Yang J, Liu P, Xu T, Yan Q, Zhang J, Zen K, Zhang CY. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell. 2010 Jul 9;39(1):133-44. doi: 10.1016/j.molcel.2010.06.010.
Results Reference
background
PubMed Identifier
20146715
Citation
Davidson-Moncada J, Papavasiliou FN, Tam W. MicroRNAs of the immune system: roles in inflammation and cancer. Ann N Y Acad Sci. 2010 Jan;1183:183-94. doi: 10.1111/j.1749-6632.2009.05121.x.
Results Reference
background
PubMed Identifier
20086171
Citation
Dang CV. Rethinking the Warburg effect with Myc micromanaging glutamine metabolism. Cancer Res. 2010 Feb 1;70(3):859-62. doi: 10.1158/0008-5472.CAN-09-3556. Epub 2010 Jan 19.
Results Reference
background
PubMed Identifier
20237418
Citation
Chan SY, Loscalzo J. MicroRNA-210: a unique and pleiotropic hypoxamir. Cell Cycle. 2010 Mar 15;9(6):1072-83. doi: 10.4161/cc.9.6.11006. Epub 2010 Mar 15.
Results Reference
background
PubMed Identifier
19278845
Citation
Williams AH, Liu N, van Rooij E, Olson EN. MicroRNA control of muscle development and disease. Curr Opin Cell Biol. 2009 Jun;21(3):461-9. doi: 10.1016/j.ceb.2009.01.029. Epub 2009 Mar 9.
Results Reference
background
PubMed Identifier
21030674
Citation
Davidsen PK, Gallagher IJ, Hartman JW, Tarnopolsky MA, Dela F, Helge JW, Timmons JA, Phillips SM. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. J Appl Physiol (1985). 2011 Feb;110(2):309-17. doi: 10.1152/japplphysiol.00901.2010. Epub 2010 Oct 28.
Results Reference
background
PubMed Identifier
17234972
Citation
Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. 2007 Feb 16;100(3):416-24. doi: 10.1161/01.RES.0000257913.42552.23. Epub 2007 Jan 18.
Results Reference
background
PubMed Identifier
17379774
Citation
van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 2007 Apr 27;316(5824):575-9. doi: 10.1126/science.1139089. Epub 2007 Mar 22.
Results Reference
background
PubMed Identifier
17210790
Citation
Boutz PL, Chawla G, Stoilov P, Black DL. MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev. 2007 Jan 1;21(1):71-84. doi: 10.1101/gad.1500707.
Results Reference
background
PubMed Identifier
16380711
Citation
Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006 Feb;38(2):228-33. doi: 10.1038/ng1725. Epub 2005 Dec 25.
Results Reference
background
PubMed Identifier
17220889
Citation
Flynt AS, Li N, Thatcher EJ, Solnica-Krezel L, Patton JG. Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate. Nat Genet. 2007 Feb;39(2):259-63. doi: 10.1038/ng1953. Epub 2007 Jan 14.
Results Reference
background
PubMed Identifier
16923828
Citation
Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A. Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol. 2006 Aug 28;174(5):677-87. doi: 10.1083/jcb.200603008. Epub 2006 Aug 21.
Results Reference
background
PubMed Identifier
17008435
Citation
McCarthy JJ, Esser KA. MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. J Appl Physiol (1985). 2007 Jan;102(1):306-13. doi: 10.1152/japplphysiol.00932.2006. Epub 2006 Sep 28.
Results Reference
background
PubMed Identifier
16489342
Citation
Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M, Cuvellier S, Harel-Bellan A. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol. 2006 Mar;8(3):278-84. doi: 10.1038/ncb1373. Epub 2006 Feb 19.
Results Reference
background
PubMed Identifier
20533884
Citation
Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79:351-79. doi: 10.1146/annurev-biochem-060308-103103.
Results Reference
background
PubMed Identifier
19440340
Citation
Safdar A, Abadi A, Akhtar M, Hettinga BP, Tarnopolsky MA. miRNA in the regulation of skeletal muscle adaptation to acute endurance exercise in C57Bl/6J male mice. PLoS One. 2009;4(5):e5610. doi: 10.1371/journal.pone.0005610. Epub 2009 May 19.
Results Reference
background
PubMed Identifier
20086200
Citation
Aoi W, Naito Y, Mizushima K, Takanami Y, Kawai Y, Ichikawa H, Yoshikawa T. The microRNA miR-696 regulates PGC-1alpha in mouse skeletal muscle in response to physical activity. Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E799-806. doi: 10.1152/ajpendo.00448.2009. Epub 2010 Jan 19.
Results Reference
background
PubMed Identifier
20724368
Citation
Nielsen S, Scheele C, Yfanti C, Akerstrom T, Nielsen AR, Pedersen BK, Laye MJ. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle. J Physiol. 2010 Oct 15;588(Pt 20):4029-37. doi: 10.1113/jphysiol.2010.189860. Erratum In: J Physiol. 2011 Mar 1;589(Pt 5):1239. Laye, Matthew [corrected to Laye, Matthew J]. J Physiol. 2015 Mar 1;593(5):1323.
Results Reference
background
PubMed Identifier
20110541
Citation
Radom-Aizik S, Zaldivar F Jr, Oliver S, Galassetti P, Cooper DM. Evidence for microRNA involvement in exercise-associated neutrophil gene expression changes. J Appl Physiol (1985). 2010 Jul;109(1):252-61. doi: 10.1152/japplphysiol.01291.2009. Epub 2010 Jan 28.
Results Reference
background
PubMed Identifier
20839489
Citation
Wessner B, Gryadunov-Masutti L, Tschan H, Bachl N, Roth E. Is there a role for microRNAs in exercise immunology? A synopsis of current literature and future developments. Exerc Immunol Rev. 2010;16:22-39.
Results Reference
background
PubMed Identifier
21690193
Citation
Baggish AL, Hale A, Weiner RB, Lewis GD, Systrom D, Wang F, Wang TJ, Chan SY. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol. 2011 Aug 15;589(Pt 16):3983-94. doi: 10.1113/jphysiol.2011.213363. Epub 2011 Jun 20.
Results Reference
background
PubMed Identifier
20084391
Citation
Camera DM, Anderson MJ, Hawley JA, Carey AL. Short-term endurance training does not alter the oxidative capacity of human subcutaneous adipose tissue. Eur J Appl Physiol. 2010 May;109(2):307-16. doi: 10.1007/s00421-010-1356-3. Epub 2010 Jan 19.
Results Reference
background
PubMed Identifier
19887595
Citation
Costford SR, Bajpeyi S, Pasarica M, Albarado DC, Thomas SC, Xie H, Church TS, Jubrias SA, Conley KE, Smith SR. Skeletal muscle NAMPT is induced by exercise in humans. Am J Physiol Endocrinol Metab. 2010 Jan;298(1):E117-26. doi: 10.1152/ajpendo.00318.2009. Epub 2009 Nov 3.
Results Reference
background
PubMed Identifier
8779956
Citation
Chesley A, Heigenhauser GJ, Spriet LL. Regulation of muscle glycogen phosphorylase activity following short-term endurance training. Am J Physiol. 1996 Feb;270(2 Pt 1):E328-35. doi: 10.1152/ajpendo.1996.270.2.E328.
Results Reference
background
PubMed Identifier
8806937
Citation
Spina RJ, Chi MM, Hopkins MG, Nemeth PM, Lowry OH, Holloszy JO. Mitochondrial enzymes increase in muscle in response to 7-10 days of cycle exercise. J Appl Physiol (1985). 1996 Jun;80(6):2250-4. doi: 10.1152/jappl.1996.80.6.2250.
Results Reference
background
PubMed Identifier
17082363
Citation
Freyssenet D. Energy sensing and regulation of gene expression in skeletal muscle. J Appl Physiol (1985). 2007 Feb;102(2):529-40. doi: 10.1152/japplphysiol.01126.2005. Epub 2006 Nov 2.
Results Reference
background
PubMed Identifier
22817841
Citation
Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab. 2012 Sep;23(9):459-66. doi: 10.1016/j.tem.2012.06.006. Epub 2012 Jul 18.
Results Reference
background
PubMed Identifier
10555139
Citation
Lowell BB. PPARgamma: an essential regulator of adipogenesis and modulator of fat cell function. Cell. 1999 Oct 29;99(3):239-42. doi: 10.1016/s0092-8674(00)81654-2. No abstract available.
Results Reference
background
PubMed Identifier
15497675
Citation
van Raalte DH, Li M, Pritchard PH, Wasan KM. Peroxisome proliferator-activated receptor (PPAR)-alpha: a pharmacological target with a promising future. Pharm Res. 2004 Sep;21(9):1531-8. doi: 10.1023/b:pham.0000041444.06122.8d.
Results Reference
background
PubMed Identifier
10913035
Citation
Horowitz JF, Leone TC, Feng W, Kelly DP, Klein S. Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. Am J Physiol Endocrinol Metab. 2000 Aug;279(2):E348-55. doi: 10.1152/ajpendo.2000.279.2.E348.
Results Reference
background
PubMed Identifier
14525942
Citation
Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, Rassoulzadegan M, Grimaldi PA. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability. FASEB J. 2003 Dec;17(15):2299-301. doi: 10.1096/fj.03-0269fje. Epub 2003 Oct 2.
Results Reference
background
PubMed Identifier
15985525
Citation
Mahoney DJ, Parise G, Melov S, Safdar A, Tarnopolsky MA. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB J. 2005 Sep;19(11):1498-500. doi: 10.1096/fj.04-3149fje. Epub 2005 Jun 28.
Results Reference
background
PubMed Identifier
10878112
Citation
Conley KE, Jubrias SA, Esselman PC. Oxidative capacity and ageing in human muscle. J Physiol. 2000 Jul 1;526 Pt 1(Pt 1):203-10. doi: 10.1111/j.1469-7793.2000.t01-1-00203.x. Erratum In: J Physiol 2001 Jun 15;533 Pt 3:921.
Results Reference
background
PubMed Identifier
21088973
Citation
Mendham AE, Donges CE, Liberts EA, Duffield R. Effects of mode and intensity on the acute exercise-induced IL-6 and CRP responses in a sedentary, overweight population. Eur J Appl Physiol. 2011 Jun;111(6):1035-45. doi: 10.1007/s00421-010-1724-z. Epub 2010 Nov 19.
Results Reference
background
PubMed Identifier
14514869
Citation
Jubrias SA, Crowther GJ, Shankland EG, Gronka RK, Conley KE. Acidosis inhibits oxidative phosphorylation in contracting human skeletal muscle in vivo. J Physiol. 2003 Dec 1;553(Pt 2):589-99. doi: 10.1113/jphysiol.2003.045872. Epub 2003 Sep 26.
Results Reference
background
PubMed Identifier
8024651
Citation
Blei ML, Conley KE, Kushmerick MJ. Separate measures of ATP utilization and recovery in human skeletal muscle. J Physiol. 1993 Jun;465:203-22. doi: 10.1113/jphysiol.1993.sp019673. Erratum In: J Physiol (Lond) 1994 Mar 15;475(3):548.
Results Reference
background
PubMed Identifier
15090482
Citation
Kim J, Heshka S, Gallagher D, Kotler DP, Mayer L, Albu J, Shen W, Freda PU, Heymsfield SB. Intermuscular adipose tissue-free skeletal muscle mass: estimation by dual-energy X-ray absorptiometry in adults. J Appl Physiol (1985). 2004 Aug;97(2):655-60. doi: 10.1152/japplphysiol.00260.2004. Epub 2004 Apr 16.
Results Reference
background
PubMed Identifier
20422397
Citation
Phielix E, Meex R, Moonen-Kornips E, Hesselink MK, Schrauwen P. Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals. Diabetologia. 2010 Aug;53(8):1714-21. doi: 10.1007/s00125-010-1764-2. Epub 2010 Apr 27.
Results Reference
background
PubMed Identifier
3593705
Citation
Veksler VI, Kuznetsov AV, Sharov VG, Kapelko VI, Saks VA. Mitochondrial respiratory parameters in cardiac tissue: a novel method of assessment by using saponin-skinned fibers. Biochim Biophys Acta. 1987 Jun 29;892(2):191-6. doi: 10.1016/0005-2728(87)90174-5.
Results Reference
background
PubMed Identifier
18663219
Citation
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8. doi: 10.1073/pnas.0804549105. Epub 2008 Jul 28.
Results Reference
background
PubMed Identifier
15983191
Citation
Sparks LM, Xie H, Koza RA, Mynatt R, Hulver MW, Bray GA, Smith SR. A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes. 2005 Jul;54(7):1926-33. doi: 10.2337/diabetes.54.7.1926.
Results Reference
background
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Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation (Columbus)
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