Muscle Protein Metabolism in Obesity

NCT01824173 | Completed Phase 1

• 1 other identifier: 12-004000
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

muscle; mitochondria; amino acids; exercise

Outcome Measures

Primary Outcomes (1)

• Rate of synthesis of muscle proteins (mixed muscle proteins, mitochondrial proteins, β-F1-ATPase)

  Measured during a 9-hour infusion study

Secondary Outcomes (1)

• β-F1-ATPase mRNA expression; PGC-1 expression

  Measured during a 9-hour infusion study

Study Arms (4)

Amino Acid Infusion in Lean

EXPERIMENTAL

Amino Acid Infusion in Lean

Other: Increase in the levels of plasma amino acids

Amino acid Infusion in Obese

EXPERIMENTAL

Amino acid Infusion in Obese

Other: Increase in the levels of plasma amino acids

Exercise in lean

EXPERIMENTAL

Exercise in lean

Other: Aerobic exercise

Exercise in Obese

EXPERIMENTAL

Exercise in Obese

Other: Aerobic exercise

Interventions

Increase in the levels of plasma amino acids OTHER

Aminosyn 15%; 160 mg/kg FFM/h for 4 hours

Amino Acid Infusion in Lean; Amino acid Infusion in Obese

Aerobic exercise OTHER

Moderate intensity for 45 minutes

Exercise in Obese; Exercise in lean

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Related Publications (4)

• 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.

  PMID: 34408662 DERIVED

• 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.

  PMID: 30253140 DERIVED

• 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.

  PMID: 29896930 DERIVED

• 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.

  PMID: 29029131 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Obesity; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Lori Roust, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Christos S Katsanos, PhD

  Arizona State University/Mayo Clinic Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: April 1, 2013
• First Posted: April 4, 2013
• Study Start: October 1, 2012
• Primary Completion: February 9, 2017
• Study Completion: February 7, 2020
• Last Updated: April 3, 2020

Record last verified: 2020-04

Locations

US (1)