Abdominal Adiposity and Muscle Mitochondrial Functions (Mithycal)
Numerous studies have demonstrated that excess perivisceral adipose tissue is associated with metabolic diseases such as insulin resistance.
In skeletal muscle, insulin resistance has been correlated with reduced mitochondrial oxidative functions. According to the actual theory, mitochondrial dysfunctions are proposed to play a causal role in the aetiology of insulin resistance. Mechanisms involve increased intramyocellular lipids storage. Yet, the causes responsible for the decline in muscle mitochondrial functions remain to be elucidated.
The investigators hypothesize that these alterations are induced by combined changes in plasma profiles of lipids and adipokines, which originate from perivisceral adipose tissue. The study aims at answering the following questions :
- Are muscle mitochondrial functions altered in association with increased perivisceral adipose tissue storage?
- Do changes in the pattern of plasma lipids and adipokines explain this correlation?
Mitochondrial Respiratory Chain Deficiencies
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Study of Interaction Between Adipose and Muscle Tissues in the Control of Muscle Mitochondrial Functions|
|Study Start Date:||April 2006|
|Study Completion Date:||January 2007|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
60 males were recruited according to waist circumference, from lean to obese values
Sixty 35 to 50-years old sedentary men will be included based on their abdominal circumference (from 75 to over 102 cm).
Body composition will be evaluated using dual-energy X-ray absorptiometry and perivisceral, intramuscular and intrahepatic adiposity will be assess by MRI and proton-NMR spectroscopy. Subjects will be also characterized by their glucose tolerance (OGTT), basal metabolism (indirect calorimetry) and maximal oxygen consumption (maximal aerobic power test on exercise bike).
Blood samples will be collected in the fasted state to assess lipids and adipokines concentrations.
Biopsies will be obtained from the vastus lateralis muscle to examine mitochondrial functions (respiration rates, ATP and superoxide anion production rates, maximal activity of oxidative enzyme). Gene expression of key enzymes, protein and transcription factors involved in lipid and energy metabolism will be assessed using real-time quantitative PCR.
Finally, whole body and muscle protein metabolism will be investigated in half of the subjects using tracer infusion (incorporation of L-[1-13C]leucine) and biopsies from vastus lateralis, both in the post-absorptive and post-prandial states (test meal)
|Centre ed Recherche en Nutrition Humaine d'Auvergne (CRNH), Unité d'Exploration Nutritionnelle, Laboratoire de Nutrition humaine|
|Clermont Ferrand, France, 63009 cedex 1|
|Principal Investigator:||Yves Boirie, PU-PH||UMR1019 INRA - Auvergne University|
|Study Director:||Beatrice Morio, PhD||UMR 1019 INRA - Auvergne University|