Clinical trial NCT01824173: Muscle Protein Metabolism in Obesity
Official title: Regulation of Muscle ATP Synthase Beta Subunit Metabolism in Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obesity
Keywords: muscle
mitochondria
amino acids
exercise
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2013-04-04
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Obesity is associated with reduced adenosine triphosphate (ATP) turnover in skeletal muscle, a condition that can impair muscle metabolism. The proposed research will discover mechanisms responsible for decreased content in mitochondrial proteins as well as in protein β-F1-ATPase, which is directly responsible for ATP assembly, in the muscle of obese individuals. This research will further examine the effectiveness of interventions, such as increased plasma amino acid availability and exercise, to increase the rate of production of mitochondrial proteins as well as that of β-F1-ATPase in the muscle of obese individuals. The findings will help to develop appropriate interventions to improve muscle ATP turnover and metabolism in obese people.


Eligibility criteria: Inclusion criteria:

1. Body mass index (BMI): lean, 19-26 kg/m2; obese, 30-40 kg/m2
2. Availability of transportation
3. Ability to sign informed consent form

Exclusion criteria:

1. Medication or supplements (i.e. amino acids, protein) known to affect protein metabolism
2. Presence of acute illness
3. History of liver disease
4. Uncontrolled metabolic disease
5. ECG documented abnormalities, atrial fibrillation, history of syncope, limiting or unstable angina, or congestive heart failure
6. Chronically elevated blood pressure (systolic, \>140 mmHg; diastolic, \>100 mmHg)
7. Cardiac pacemaker or other medical device implanted in the body
8. Low hemoglobin or hematocrit
9. Current participation in a weight-loss regimen, including extreme dietary practices
10. Smoking
11. Use of anabolic steroids or corticosteroids (within 3 months)

Primary outcomes:
measure: Rate of synthesis of muscle proteins (mixed muscle proteins, mitochondrial proteins, β-F1-ATPase)
timeFrame: Measured during a 9-hour infusion study
Secondary outcomes:
measure: β-F1-ATPase mRNA expression; PGC-1 expression
timeFrame: Measured during a 9-hour infusion study
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
Study officials:
affiliation: Mayo Clinic
name: Lori Roust, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arizona State University/Mayo Clinic Arizona
name: Christos S Katsanos, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Serrano N, Tran L, Hoffman N, Roust L, De Filippis EA, Carroll CC, Patel SH, Kras KA, Buras M, Katsanos CS. Lack of Increase in Muscle Mitochondrial Protein Synthesis During the Course of Aerobic Exercise and Its Recovery in the Fasting State Irrespective of Obesity. Front Physiol. 2021 Aug 2;12:702742. doi: 10.3389/fphys.2021.702742. eCollection 2021.
citation: Kras KA, Langlais PR, Hoffman N, Roust LR, Benjamin TR, De Filippis EA, Dinu V, Katsanos CS. Obesity modifies the stoichiometry of mitochondrial proteins in a way that is distinct to the subcellular localization of the mitochondria in skeletal muscle. Metabolism. 2018 Dec;89:18-26. doi: 10.1016/j.metabol.2018.09.006. Epub 2018 Sep 22.
citation: Tran L, Kras KA, Hoffman N, Ravichandran J, Dickinson JM, D'Lugos A, Carroll CC, Patel SH, Mandarino LJ, Roust L, Katsanos CS. Lower Fasted-State but Greater Increase in Muscle Protein Synthesis in Response to Elevated Plasma Amino Acids in Obesity. Obesity (Silver Spring). 2018 Jul;26(7):1179-1187. doi: 10.1002/oby.22213. Epub 2018 Jun 12.
citation: Kras KA, Hoffman N, Roust LR, Patel SH, Carroll CC, Katsanos CS. Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4515-4525. doi: 10.1210/jc.2017-01201.