Abdominal Adiposity and Muscle Mitochondrial Functions

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?

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Key information

Conditions

Mitochondrial Respiratory Chain Deficiencies Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Mitochondrial Diseases Nutritional and Metabolic Diseases

Age range

35 year–50 year

Sex eligibility

Male

Study type

Observational

Primary location

Centre ed Recherche en Nutrition Humaine d'Auvergne (CRNH), Unité d'Exploration Nutritionnelle, Laboratoire de Nutrition humaine

Clermont-Ferrand, 63009 cedex 1, France

About this study

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)

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Male subjects
Age between 35 and 50
waist circumference > 75 cm
Baecke score < 1 (activity score for sedentary subjects)
Subjects giving written informed consent
Subjects willing to comply with the study procedures
Subjects considered as normal after clinical examination and medical questionnaire

Exclusion criteria

Weight change > 3 kg within 3 months prior to study
Patients with type 1 or type 2 diabetes
Serologic evidence of active hepatitis B or HIV
History of cancer or significant intestinal, hepatic, renal or cardiovascular disorders within the past 5 years
History of systemic infections or inflammatory diseases within the past 2 months
Hypocaloric or special diets (e.g. vegetarian)
Patients currently known to abuse or to be dependent on any drug, including alcohol (daily consumption > 20g) and tobacco (daily consumption > 5 cigarettes)
CRP < 5 mg/L
Blood coagulation disorders
Allergy to xylocaïne
for test meal : Food allergy (particularly milk allergy and lactose intolerance)
for MRI : Claustrophobia

Sponsors and collaborators

Lead sponsor

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Other

Registry information

Official study title

Study of Interaction Between Adipose and Muscle Tissues in the Control of Muscle Mitochondrial Functions

Acronym: Mithycal

Important dates

Study start: 2006
Primary completion: 2006
Study completion: 2007
First posted: Mar 13, 2007
Registry last updated: Sep 19, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed