Effect of Obesity-derived Cytokines on Protein Turnover and Carbohydrate Metabolism in Human Skeletal Muscle

Summary

Obesity in humans has been shown to result in the increased release of small inflammatory-inducing proteins, called cytokines, from the fat cells of the body. The investigators are interested in the effects of these cytokines on the mechanisms that control muscle mass and metabolism in the obese human. Previous research from work in cells and animals has shown the cytokines reduce the synthesis of muscle proteins and simultaneously enhance their rate of breakdown, resulting in a loss of muscle mass. Furthermore, research suggests that the same cytokines may inhibit carbohydrate oxidation, a pivotal step in muscle metabolism. However, despite these potential negative consequences for skeletal muscle function, the effect of low-level and persistent inflammation as seen in obese humans, remains largely unknown.

In the current study, the investigators plan to measure the rates of synthesis and breakdown of muscle proteins in conjunction with rates of carbohydrate oxidation in obese older participants, and compare them to rates determined in healthy non-obese individuals. Furthermore, participants will undergo a 12-week course of either pioglitazone, an insulin sensitiser often prescribed to type II diabetics, or a placebo. Pioglitazone has been shown previously to normalise the levels of cytokines in the blood of chronically inflamed individuals. By repeating after the 12-week intervention period the initial measurements described above, and by accurately determining the levels of the cytokines, the identification of the negative effects of obesity-induced inflammation in older adults on muscle metabolism will be determined.

Conditions

• Obesity
• Sarcopenia

Interventions

OTHER

[2H5]phenylalanine

Administered to allow the determination of leg protein breakdown rates in study visits. Description of amount administered provided elsewhere.

OTHER

[1-13C]leucine

Administered to allow the determination of muscle protein synthesis rates in study visits. Description of amount administered provided elsewhere.

DRUG

Pioglitazone

Described elsewhere

DRUG

Insulin

Administered to simulate the feeding response in study visits. Description of amount administered provided elsewhere.

DRUG

Octreotide

Administered to simulate the feeding response in study visits. Description of amount administered provided elsewhere.

DRUG

Glucose

Administered to simulate the feeding response in study visits. Description of amount administered provided elsewhere.

DRUG

Mixed Amino Acids

Administered to simulate the feeding response in study visits. Description of amount administered provided elsewhere.

Sponsors & Collaborators

• Biotechnology and Biological Sciences Research Council

  collaborator OTHER

• University of Nottingham

  lead OTHER

Principal Investigators

• Paul L Greenhaff, PhD · The University of Nottingham

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

55 Years

Max Age

75 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-10-31

Primary Completion

2011-10-31

Completion

2012-09-30

Countries

• United Kingdom

Study Locations