Ignite Creation Date:
2024-05-06 @ 1:23 AM
Last Modification Date:
2024-10-26 @ 11:03 AM
Study NCT ID:
NCT01793896
Status:
TERMINATED
Last Update Posted:
2018-02-14
First Post:
2013-02-11
Brief Title:
Beneficial Effects of Exercise and Healthy Diets on Muscle and Adipose Tissue
Sponsor:
University of Chile
Organization:
University of Chile
Study Overview
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
Status:
TERMINATED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Serious difficulties for patient recruitment
to recruit patients
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 andor 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 LS14to factors secreted by media conditioned by the patients adipose tissue explants 2 A prospective intervention in overweightmoderately 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-78-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
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 kgmt2
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 gday
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 haemoglobinlipoproteins creatinineprothrombin 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 HE for histologic estimation of adipocyte cell size
II - INTERVENTION STUDY This section intends to demonstrate the effects of a low-AGEs Mediterranean diet andor exercise over skeletal muscle metabolic profile and adipogenicinflammatory 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 gday
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 andor physical exercise during 3 months After signing a written informed consentsubjects 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
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 kgmt2
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 gday
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 haemoglobinlipoproteins creatinineprothrombin 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 HE for histologic estimation of adipocyte cell size
II - INTERVENTION STUDY This section intends to demonstrate the effects of a low-AGEs Mediterranean diet andor exercise over skeletal muscle metabolic profile and adipogenicinflammatory 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 gday
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 andor physical exercise during 3 months After signing a written informed consentsubjects 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| INSTITUTE OF NUTRITION 2013 | OTHER | INTA | None |