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

• Status: Completed
• Trial end date: 2012-09-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Nottingham
• Collaborator: Biotechnology and Biological Sciences Research Council
• Treatments: Insulin; Insulin, Globin Zinc; Octreotide; Pioglitazone

Criteria

Inclusion Criteria:

• Male

• 55-75 years old

• Body Mass Index 20-25 or >30 kg/m2

• Residing in Nottinghamshire area

Exclusion Criteria:

• Taking statin medication

• Clotting disorders of previous central venous access (CVA) / thrombosis-inducing activity (TIA)/ deep vein thrombosis (DVT)

• Metabolic disease e.g. diabetes, thyroid dysfunction

• Inflammatory conditions e.g. Rheumatoid Arthritis, Crohn's Disease

• Tobacco smoker in previous 3 years

• Lower limb circulation problems e.g. Claudication

• Epilepsy

• Renal pathology

• Respiratory problems including asthma