Beneficial Effects of Exercise and Healthy Diets on Muscle and Adipose Tissue

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2013 by University of Chile
Sponsor:
Information provided by (Responsible Party):
MARIA PIA DE LA MAZA, University of Chile
ClinicalTrials.gov Identifier:
NCT01793896
First received: February 11, 2013
Last updated: February 18, 2013
Last verified: February 2013
  Purpose

Both dietary caloric restriction (CR) and physical exercise (PE) exert beneficial effects, which retard or prevent age-related diseases and prolong life span. Subjects with the metabolic syndrome age prematurely, therefore preventive measures should be initiated early. The present study intends to demonstrate that physical exercise and/or Mediterranean diet, in middle aged volunteers with the metabolic syndrome, preserve adequate adipose tissue functionality and retard skeletal muscle aging (assessed by mitochondrial biogenesis and accumulation of ROS), by activating several pathways, homologous to CR. The investigators plan to study this by using two approaches: 1) A cross- sectional model, in which the expression of the mentioned metabolic mediators, indicators of muscle mitochondrial biogenesis and muscle oxidative damage will be compared between men with different body compositions, fat distribution, muscle strength and exercise capacity (VO2max). Also, in these men the investigators will assess the expression of uncoupling protein 1 (UCP1) in subcutaneous white adipose tissue (as a measure of adaptive thermogenesis), and inflammatory markers (Interleukin 1-6, Interleukin 1ß and CCL2 chemokine (C-C motif ligand 2)) in preperitoneal adipose tissue, plus inflammation and adipogenesis potential of their cultured preadipocytes. Moreover, in vitro studies will evaluate the functional effects of exposure of a cell lyne of human adipocyte cells (LS14)to factors secreted by media conditioned by the patients´ adipose tissue explants. 2) A prospective intervention in overweight/moderately obese middle aged volunteers that will be assigned to a weight-maintenance period (as a control group), and then randomly y assigned to a Mediterranean diet, exercise training or diet plus training. Before and after 3 months of intervention the investigators will obtain muscle tissue samples to study the expression of Peroxisome proliferator activated receptor (PPAR) gamma coactivator 1 alpha (PGC1), uncoupling protein 3 (UCP3), AMP activated protein kinase (AMPK), Sirtuin 1 (SIRT-1), mitochondrial DNA and oxidative damage indicators (8-oxo-7,8-dihydro-2-deoxyguanosine (oxodG), carboxymethyllysine (CML and its receptor (RAGE)). In vitro studies will evaluate the effect of circulating factors from the patients (serum) on LS14 inflammatory and adipogenic potential, at baseline and after 3 months of intervention.


Condition Intervention
Metabolic Syndrome
Behavioral: Control period
Behavioral: Diet Group
Behavioral: Exercise group
Behavioral: Diet + Exercise

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Mitochondrial Biogenesis, Reduction of Muscle Oxidative Damage and Improvement in Adipose Tissue Functional Profile, Account for the Beneficial Effects of Exercise and Healthy Diets

Resource links provided by NLM:


Further study details as provided by University of Chile:

Primary Outcome Measures:
  • Change in mitochondrial density in muscle tissue [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    As described in the methodology section


Secondary Outcome Measures:
  • Change in Oxidative damage in muscle tissue [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    As described in the methodology section


Estimated Enrollment: 115
Study Start Date: July 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: control period
control period with no intervention. Comparison of parameters at entrance and one month later without any intervention
Behavioral: Control period
Analysis at recruitment and after a month without any intervention
Other Name: Before randomization
Experimental: Diet group
Mediterranean diet prescription during 3 months
Behavioral: Diet Group
selected subjects will adopt a Mediterranean low-AGE diet. We will not include red wine in the Mediterranean diet (7 Kilocalories (KCal)/g), in order to attain more weight loss. Each subject will be instructed to reduce 500 Kcal of their estimated total daily energy requirements, so theoretically they will be able to reduce 5 - 10 % of their body weight in 3 months.
Other Name: Mediterranean diet
Experimental: Exercise group
Subjects will be trained 3 times a week during 3 months
Behavioral: Exercise group
The intervention will consist of 3 weekly 1 hour sessions (5 minutes of preconditioning, followed by 20 minutes cycling, brisk walking or jogging at 65-70 % maximal aerobic capacity, then 25 minutes resistance weight-lifting exercises and finally 10 minutes of stretching). Exercise intensity will be increased weekly according to the Borg Scale intensity. The exercise intervention will be supervised by physical education teachers, registering attendance at every session.
Experimental: Diet + Exercise
Both a dietary prescription plus exercise training during 3 months
Behavioral: Diet + Exercise
these patients will be incorporated to receive both Mediterranean diet plus exercise interventions

  Hide Detailed Description

Detailed Description:

METHODOLOGY:

This study will be composed of 2 parts:

I - CROSS SECTIONAL STUDY The aim of this section is to compare men with different body compositions, fat distribution and exercise capacity with respect to their muscle mitochondrial biogenesis, oxidative damage and energy flux regulator molecules, together with their adipose tissue inflammation, adipokine expression and thermogenic potential.

Inclusion criteria :

  • male sex
  • age 25 - 50 years
  • BMI from 20 - 35 kg/mt2
  • indication for surgery of an inguinal hernia

Exclusion criteria:

  • diabetes mellitus
  • chronic neuromuscular or neurological deficits precluding normal physical activity
  • heavy smoking (> 5 cigarettes per day)
  • alcohol intake > 30 g/day
  • chronic diseases such as cancer, HIV-AIDS, renal, pulmonary, cardiac or hepatic conditions.

Before the operation and after signing a written informed consent, the following assessment will be performed:

  1. Medical history including medication intake and complete physical examination.
  2. Dietary recall of habitual intake and calculation of AGEs ingestion.
  3. Regular physical activity assessment using the International Physical Activity Questionnaire
  4. Anthropometrics (height, weight, waist circumference)
  5. Fasting blood sampling for routine determinations (haemoglobin,lipoproteins, creatinine,prothrombin, TSH), AGEs concentrations (CML) free fatty acids, adiponectin and 8- Isoprostanes.
  6. Fasting and post glucose serum sampling for glucose and insulin measurements, and calculation of Homeostasis Model Assessment (HOMA-IR) and the Matsuda Index for determination of peripheral insulin sensitivity.
  7. Resting and exercise indirect calorimetry for estimation of resting energy expenditure, respiratory quotient and VO2 max.
  8. Handgrip and quadriceps muscle strength
  9. Dual X-Ray Energy Densitometry (DEXA) for estimation of body composition
  10. CT scan of abdominal region at L4 level for measurement of visceral and subcutaneous fat areas and estimation of liver fat infiltration.
  11. Ultrasound intensity analysis in thigh ultrasonography indicating muscle fat infiltration. After the initial evaluation, subjects will be classified as with or without the metabolic syndrome, according to the international guidelines guidelines, for further analysis of data.

A few days later, during the surgical procedure, a sample of muscle tissue (approximately 200 mg of internal abdominal oblique) will be obtained for measurement of:

  1. Fiber type
  2. Messenger Ribonucleic acid (mRNA) expression of PGC-1-alpha, SIRT-1, UCP-3 and AMPK
  3. Mitochondrial density by measurement of mitDNA and Cytochrome C activity
  4. Oxidative damage (8-oxodG, CML and RAGE).

During the same operation, 2 samples of adipose tissue will also be obtained, one subcutaneous (at the site of the incision) and the other preperitoneal (at the inguinal sac), for in vitro studies:

  1. UCP1 and inflammatory marker (interleukin 6, 1ß, CCL2) expression in mature adipocytes
  2. Inflammatory profile and adipogenic potential (expression of lipoprotein lipase, PPAR gamma and adiponectin) in cultured preadipocytes
  3. Adipogenic potential and inflammatory expression profile of LS14 adipose cells exposed to conditioned media from adipose tissue explants.

A small part of these adipose tissue samples will be placed in formaldehyde, fixed and stained with H.E for histologic estimation of adipocyte cell size.

II - INTERVENTION STUDY This section intends to demonstrate the effects of a low-AGEs Mediterranean diet and/or exercise, over skeletal muscle metabolic profile and adipogenic/inflammatory features of adipocytes.

Inclusion criteria:

  • Overweight or obese men and women
  • Ages 25 - 50 years
  • Interest in losing weight

Exclusion criteria:

  • weight fluctuations (> 3 k in the last 3 months)
  • diabetes mellitus
  • chronic neuromuscular or neurologic diseases
  • heavy smoking (> 5 cigarettes per day)
  • alcohol intake > 30 g/day
  • chronic diseases such as cancer, HIV, renal, pulmonary, cardiac or hepatic conditions.

Subjects will be invited to participate in a trial using a Mediterranean low-AGEs diet and/or physical exercise during 3 months. After signing a written informed consent,subjects will be allocated to one of these interventions, which will be randomly selected, and the following assessment will be performed, at baseline and after 3 months of intervention:

  1. Medical and medication intake history and complete physical examination.
  2. Dietary recall of habitual intake and calculation of AGEs ingestion.
  3. Physical activity questionnaire (IPAQ)
  4. Anthropometrics (height, weight, waist circumference)
  5. Fasting blood sampling for routine determinations (haemoglobin, lipoproteins, creatinine, prothrombin and TSH), AGEs concentrations (CML), free fatty acids, adiponectin, 8-Isoprostanes and serum for in vitro adipose tissue studies (see below).
  6. Fasting and post glucose blood sampling for glucose and insulin measurements, and calculation of HOMA-IR and the Matsuda Index for determination of peripheral insulin sensitivity.
  7. Dual X-Ray Energy Densitometry (DEXA) for estimation of body composition
  8. CT scan of abdominal region at L4 level for measurement of visceral and subcutaneous fat areas and estimation of liver fat infiltration
  9. Resting and exercise indirect calorimetry for estimation of resting energy expenditure, respiratory quotient and VO2 max.
  10. Handgrip and quadriceps muscle strength
  11. Ultrasound intensity analysis in thigh indicating muscle fat infiltration
  12. Ultrasound guided quadriceps muscle biopsy to measure mitochondrial density (mitDNA) and expression of PGC-1
  Eligibility

Ages Eligible for Study:   25 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

CROSS SECTIONAL: male sex, age 25 -50 years, with BMI ranging from 20 to 35 kg/mt2. INTERVENTION STUDY: Overweight or obese men and women aged 25 - 50 years interested in losing weight,will

Exclusion Criteria:

CROSS SECTIONAL : diabetes mellitus, chronic neuromuscular or neurological deficits precluding normal physical activity, heavy smoking (> 5 cigarettes per day), alcohol intake > 30 g/day and chronic diseases such as cancer, HIV-AIDS, renal, pulmonary, cardiac or hepatic conditions.

INTERVENTION STUDY: weight fluctuations (> 3 k in the last 3 months), diabetes mellitus, chronic neuromuscular or neurologic diseases, heavy smoking (> 5 cigarettes per day) and alcohol intake > 30 g/day, and chronic diseases such as cancer, HIV, renal, pulmonary, cardiac or hepatic conditions.

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01793896

Contacts
Contact: Maria Pia de la Maza, Professor 56229781400 ext 1502 mpmaza@inta.uchile.cl
Contact: Daniel Bunout, Professor 56229781400 ext 1495 dbunout@inta.uchile.cl

Locations
Chile
Institute of Nutrition & Food Technology (INTA) Not yet recruiting
Santiago, Metropolitan Region, Chile, 7830490
Contact: Maria Pia de la Maza, Professor    56229781400 ext 1502    mpmaza@inta.uchile.cl   
Sub-Investigator: Daniel Bunout, Professor         
Sponsors and Collaborators
University of Chile
Investigators
Principal Investigator: Maria Pia de la Maza, Professor University of Chile
  More Information

No publications provided

Responsible Party: MARIA PIA DE LA MAZA, Professor, University of Chile
ClinicalTrials.gov Identifier: NCT01793896     History of Changes
Other Study ID Numbers: Fondecyt 1130284, INSTITUTE OF NUTRITION 2013
Study First Received: February 11, 2013
Last Updated: February 18, 2013
Health Authority: Chile: Comisión Nacional de Investigación Científica y Tecnológica

Keywords provided by University of Chile:
Metabolic syndrome
Ageing
Mitochondrial density
Oxidative damage
Inflammatory mediators
AMPK
Adipogenesis

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 28, 2014