Abdominal Adiposity and Muscle Mitochondrial Functions - Full Text View

Sponsored by:	French National Institute for Agricultural Research
Information provided by:	French National Institute for Agricultural Research
ClinicalTrials.gov Identifier:	NCT00446745

Purpose

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?

Condition
Mitochondrial Respiratory Chain Deficiencies

Genetics Home Reference related topics: mitochondrial neurogastrointestinal encephalopathy disease

MedlinePlus related topics: Metabolic Disorders

U.S. FDA Resources

Study Type:	Observational
Study Design:	Prospective
Official Title:	Study of Interaction Between Adipose and Muscle Tissues in the Control of Muscle Mitochondrial Functions

Further study details as provided by French National Institute for Agricultural Research:

Estimated Enrollment:	60
Study Start Date:	April 2006
Estimated Study Completion Date:	January 2007

Detailed Description:

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)

Eligibility

Ages Eligible for Study:	35 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00446745

Locations

France
Centre ed Recherche en Nutrition Humaine d'Auvergne (CRNH), Unité d'Exploration Nutritionnelle, Laboratoire de Nutrition humaine
Clermont Ferrand, France, 63009 cedex 1

Sponsors and Collaborators

French National Institute for Agricultural Research

Investigators

Principal Investigator:	Yves Boirie, PU-PH	UMR1019 INRA - Auvergne University
Study Director:	Beatrice Morio, PhD	UMR 1019 INRA - Auvergne University

More Information

ANR consortium website This link exits the ClinicalTrials.gov site

Human Nutrition Unit website This link exits the ClinicalTrials.gov site

Publications:

Chanseaume E, Tardy AL, Salles J, Giraudet C, Rousset P, Tissandier A, Boirie Y, Morio B. Chronological approach of diet-induced alterations in muscle mitochondrial functions in rats. Obesity (Silver Spring). 2007 Jan;15(1):50-9.

Chanseaume E, Malpuech-Brugere C, Patrac V, Bielicki G, Rousset P, Couturier K, Salles J, Renou JP, Boirie Y, Morio B. Diets high in sugar, fat, and energy induce muscle type-specific adaptations in mitochondrial functions in rats. J Nutr. 2006 Aug;136(8):2194-200.

Study ID Numbers:	AU628
Study First Received:	March 9, 2007
Last Updated:	January 13, 2009
ClinicalTrials.gov Identifier:	NCT00446745
Health Authority:	France: Ministry of Health

Keywords provided by French National Institute for Agricultural Research:

Nutritional and Metabolic Diseases
Insulin resistance
Energy Metabolisms
Skeletal muscle
Visceral Adipose Tissue

Study placed in the following topic categories:

Obesity
Metabolic Diseases
Insulin Resistance

Metabolic disorder
Mitochondrial Diseases
Insulin

ClinicalTrials.gov processed this record on February 11, 2009