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:
Participant gender:
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
Details
Lead Sponsor:
University of Nottingham
Collaborator:
Biotechnology and Biological Sciences Research Council