Obesity, Inflammation and Aging: Effects of Physical Exercise and Omega-3 Fatty Acids. (OBELEX)

Dysfunction of Adipose Tissue in Obesity, Inflammation and Aging: Mechanisms and Effects of Physical Exercise and Omega-3 Fatty Acids.

Dysfunction of adipose tissue in obesity, inflammation and aging: mechanisms and effects of physical exercise and omega-3 fatty acids.

Study Overview

Detailed Description

Obesity is associated with the development of metabolic diseases including type 2 diabetes and immune disorders. Obesity also leads to reduced lifespan and accelerated cellular processes similar to those of aging. On the other hand, aging is accompanied by the accumulation of visceral fat and the metabolic complications associated to obesity. Both obesity and aging have been identified as chronic, low-grade inflammation disorders. The inflammation in aging has been considered as a risk factor for the development of most of age-related diseases, and therefore for morbidity and mortality in the elderly. However, the specific mechanisms leading to inflammation in aging remain largely unknown.

Resolution of inflammation is an active process which involves production of several series of specialized pro-resolving lipid mediators such lipoxins, resolvin, protectins and maresin. The hypothesis of this trial is that the chronic inflammation associated to obesity and aging could be the result of an impaired production of these specialized pro-resolutive lipid mediators, mainly in adipose tissue. On the other hand, the investigators also propose that altered transcriptional pattern might be responsible for the development of the inflammation associated with the pathophysiology of obesity and aging. Therefore the first general aim of the current project will be to characterize the mechanisms involved in the unresolved chronic inflammation that arises during obesity and aging.

Because n-3 PUFAs (polyunsaturated fatty acids) serve as substrates for the synthesis of specialized pro-resolving lipid mediators and are important transcriptional regulators, the investigators propose that dietary supplementation with n-3 PUFAs, alone or in combination with regular physical exercise could promote the resolution of local and systemic inflammation and the subsequent metabolic disorders associated to obesity and aging. A trial in overweight/obese postmenopausal women will be carried out to characterize the potential beneficial effects of regular administration of a DHA-rich dietary supplement and/or a progressive resistance training (PRT) program on weight and fat mass loss, insulin sensitivity, inflammatory markers and gene/miRNA/lipidomic/metabolomic profile in serum and/or adipose tissue. Moreover, changes in gut microbiota will be also addressed.

Study Type

Interventional

Enrollment (Actual)

85

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Department of Nutrition, Food Science and Physiology. Centre for Nutrition Research.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Post-menopausal women
  • Age between 55 and 70 years
  • Body Mass Index (BMI) between 27.5 and 35 kg/m²
  • Weight unchanged (± 3 kg) for the last 3 months
  • Overall physical and psychological condition that the investigator believes is in accordance with the overall aim of the study

Exclusion Criteria:

  • Use of regular prescription medication: specially statins, antidiabetic drugs, menopausal hormone replacement therapy
  • To suffer from any chronic metabolic condition: severe dislipidemia, type 1 or 2 diabetes, hepatic (cirrhosis), renal disease, cardiovascular disease, neuromuscular disease, arthritic disease, pulmonary disease and/or other debilitating diseases
  • Food allergies and/or food intolerance expected to come up during the study
  • Following special diets (Atkins, vegetarian, etc.) prior three months the start of the study
  • Eating disorders
  • Surgically treated obesity
  • Alcohol or drug abuse

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control
Dietary advice for a healthy diet supplemented with placebo (olive oil).
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
Experimental: Omega-3
Dietary advice for a healthy diet supplemented with DHA-rich dietary supplement (providing 1.650 mg/day of DHA).
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
Experimental: Resistance Training
Dietary advice for a healthy diet supplemented with placebo (olive oil) and moderate resistance training program.
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
Experimental: Omega-3 + Resistance Training
Dietary advice for a healthy diet supplemented with a DHA-rich dietary supplement (providing 1.650 mg/day of DHA) and moderate resistance training program.
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fat mass reduction
Time Frame: Week 0 (baseline)
Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA).
Week 0 (baseline)
Fat mass reduction
Time Frame: Week 16 (end of intervention)
Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA).
Week 16 (end of intervention)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evolution of fat mass reduction
Time Frame: Week 0 (baseline)
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 0 (baseline)
Evolution of fat mass reduction
Time Frame: Week 2
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 2
Evolution of fat mass reduction
Time Frame: Week 4
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 4
Evolution of fat mass reduction
Time Frame: Week 6
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 6
Evolution of fat mass reduction
Time Frame: Week 8
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 8
Evolution of fat mass reduction
Time Frame: Week 10
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 10
Evolution of fat mass reduction
Time Frame: Week 12
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 12
Evolution of fat mass reduction
Time Frame: Week 14
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 14
Evolution of fat mass reduction
Time Frame: Week 16 (end of intervention)
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Week 16 (end of intervention)
Weight loss
Time Frame: Week 0 (baseline)
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 0 (baseline)
Weight loss
Time Frame: Week 2
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 2
Weight loss
Time Frame: Week 4
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 4
Weight loss
Time Frame: Week 6
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 6
Weight loss
Time Frame: Week 8
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 8
Weight loss
Time Frame: Week 10
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 10
Weight loss
Time Frame: Week 12
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 12
Weight loss
Time Frame: Week 14
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 14
Weight loss
Time Frame: Week 16 (end of intervention)
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Week 16 (end of intervention)
Evolution of body composition
Time Frame: Week 0 (baseline)
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 0 (baseline)
Evolution of body composition
Time Frame: Week 2
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 2
Evolution of body composition
Time Frame: Week 4
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 4
Evolution of body composition
Time Frame: Week 6
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 6
Evolution of body composition
Time Frame: Week 8
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 8
Evolution of body composition
Time Frame: Week 10
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 10
Evolution of body composition
Time Frame: Week 12
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 12
Evolution of body composition
Time Frame: Week 14
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 14
Evolution of body composition
Time Frame: Week 16 (end of intervention)
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Week 16 (end of intervention)
Hip circumference
Time Frame: Week 0 (baseline)
Hip circumference will be measured with a measuring tape.
Week 0 (baseline)
Hip circumference
Time Frame: Week 8
Hip circumference will be measured with a measuring tape.
Week 8
Hip circumference
Time Frame: Week 16 (end of intervention)
Hip circumference will be measured with a measuring tape.
Week 16 (end of intervention)
Neck circumference
Time Frame: Week 0 (baseline)
Neck circumference will be measured with a measuring tape.
Week 0 (baseline)
Neck circumference
Time Frame: Week 8
Neck circumference will be measured with a measuring tape.
Week 8
Neck circumference
Time Frame: Week 16 (end of intervention)
Neck circumference will be measured with a measuring tape.
Week 16 (end of intervention)
Waist circumference
Time Frame: Week 0 (baseline)
Waist circumference will be measured with a measuring tape.
Week 0 (baseline)
Waist circumference
Time Frame: Week 8
Waist circumference will be measured with a measuring tape.
Week 8
Waist circumference
Time Frame: Week 16 (end of intervention)
Waist circumference will be measured with a measuring tape.
Week 16 (end of intervention)
Abdomen circumference
Time Frame: Week 0 (baseline)
Abdomen circumference will be measured with a measuring tape.
Week 0 (baseline)
Abdomen circumference
Time Frame: Week 8
Abdomen circumference will be measured with a measuring tape.
Week 8
Abdomen circumference
Time Frame: Week 16 (end of intervention)
Abdomen circumference will be measured with a measuring tape.
Week 16 (end of intervention)
Arm circumference
Time Frame: Week 0 (baseline)
Arm circumference will be measured with a measuring tape.
Week 0 (baseline)
Arm circumference
Time Frame: Week 8
Arm circumference will be measured with a measuring tape.
Week 8
Arm circumference
Time Frame: Week 16 (end of intervention)
Arm circumference will be measured with a measuring tape.
Week 16 (end of intervention)
Midthigh circumference
Time Frame: Week 0 (baseline)
Midthigh circumference will be measured with a measuring tape.
Week 0 (baseline)
Midthigh circumference
Time Frame: Week 8
Midthigh circumference will be measured with a measuring tape.
Week 8
Midthigh circumference
Time Frame: Week 16 (end of intervention)
Midthigh circumference will be measured with a measuring tape.
Week 16 (end of intervention)
Midcalf circumference
Time Frame: Week 0 (baseline)
Midcalf circumference will be measured with a measuring tape.
Week 0 (baseline)
Midcalf circumference
Time Frame: Week 8
Midcalf circumference will be measured with a measuring tape.
Week 8
Midcalf circumference
Time Frame: Week 16 (end of intervention)
Midcalf circumference will be measured with a measuring tape.
Week 16 (end of intervention)
Triceps skinfold
Time Frame: Week 0 (baseline)
Triceps skinfold will be measured with a caliper.
Week 0 (baseline)
Triceps skinfold
Time Frame: Week 8
Triceps skinfold will be measured with a caliper.
Week 8
Triceps skinfold
Time Frame: Week 16 (end of intervention)
Triceps skinfold will be measured with a caliper.
Week 16 (end of intervention)
Thigh skinfold
Time Frame: Week 0 (baseline)
Thigh skinfold will be measured with a caliper.
Week 0 (baseline)
Thigh skinfold
Time Frame: Week 8
Thigh skinfold will be measured with a caliper.
Week 8
Thigh skinfold
Time Frame: Week 16 (end of intervention)
Thigh skinfold will be measured with a caliper.
Week 16 (end of intervention)
Medial calf skinfold
Time Frame: Week 0 (baseline)
Medial calf skinfold will be measured with a caliper.
Week 0 (baseline)
Medial calf skinfold
Time Frame: Week 8
Medial calf skinfold will be measured with a caliper.
Week 8
Medial calf skinfold
Time Frame: Week 16 (end of intervention)
Medial calf skinfold will be measured with a caliper.
Week 16 (end of intervention)
Blood pressure
Time Frame: Week 0 (baseline)
Systolic and diastolic blood pressure will be measured with a tensiometer.
Week 0 (baseline)
Blood pressure
Time Frame: Week 8
Systolic and diastolic blood pressure will be measured with a tensiometer.
Week 8
Blood pressure
Time Frame: Week 16 (end of intervention)
Systolic and diastolic blood pressure will be measured with a tensiometer.
Week 16 (end of intervention)
Serum glucose
Time Frame: Week 0 (baseline)
Fasting serum glucose will be measured after overnight fast.
Week 0 (baseline)
Serum glucose
Time Frame: Week 16 (end of intervention)
Fasting serum glucose will be measured after overnight fast.
Week 16 (end of intervention)
Serum insulin
Time Frame: Week 0 (baseline)
Fasting serum insulin will be measured after overnight fast.
Week 0 (baseline)
Serum insulin
Time Frame: Week 16 (end of intervention)
Fasting serum insulin will be measured after overnight fast.
Week 16 (end of intervention)
Oral Glucose Tolerance Test
Time Frame: Week 0 (baseline)
Oral Glucose Tolerance Test will be carried out after overnight fast.
Week 0 (baseline)
Oral Glucose Tolerance Test
Time Frame: Week 16 (end of intervention)
Oral Glucose Tolerance Test will be carried out after overnight fast.
Week 16 (end of intervention)
Lipid metabolism biomarkers
Time Frame: Week 0 (baseline)
Serum free fatty acids, triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations will be measured after an overnight fast.
Week 0 (baseline)
Lipid metabolism biomarkers
Time Frame: Week 16 (end of intervention)
Serum free fatty acids, triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations will be measured after an overnight fast.
Week 16 (end of intervention)
Ketone bodies
Time Frame: Week 0 (baseline)
Ketone bodies concentrations will be measured after an overnight fast.
Week 0 (baseline)
Ketone bodies
Time Frame: Week 16 (end of intervention)
Ketone bodies concentrations will be measured after an overnight fast.
Week 16 (end of intervention)
Thyroid function (body metabolism)
Time Frame: Week 0 (baseline)
TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits
Week 0 (baseline)
Thyroid function (body metabolism)
Time Frame: Week 16 (end of intervention)
TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits
Week 16 (end of intervention)
Cardiovascular risk biomarkers
Time Frame: Week 0 (baseline)
PAI-1 (plasminogen activator inhibitor-1), ADMA (asymmetric dimethylarginine) and VEGF (vascular endothelial growth factor) will be measured in plasma using ELISA kits
Week 0 (baseline)
Cardiovascular risk biomarkers
Time Frame: Week 16 (end of intervention)
PAI-1 (plasminogen activator inhibitor-1), ADMA (asymmetric dimethylarginine) and VEGF (vascular endothelial growth factor) will be measured in plasma using ELISA kits
Week 16 (end of intervention)
Inflammation biomarkers
Time Frame: Week 0 (baseline)
TNF-α (tumour necrosis factor-alpha), IL-6 (interleukin 6), C-reactive protein, serum A-amyloid, leptin, adiponectin, chemerin will be measured by ELISA kits
Week 0 (baseline)
Inflammation biomarkers
Time Frame: Week 16 (end of intervention)
TNF-α (tumour necrosis factor-alpha), IL-6 (interleukin 6), C-reactive protein, serum A-amyloid, leptin, adiponectin, chemerin will be measured in plasma by ELISA kits
Week 16 (end of intervention)
Satiety and eating behavior traits
Time Frame: Week 0 (baseline)
Satiety will be also estimated by using a VAS (visual analogue scale) questionnaire and eating behavior traits will be also evaluated with validated questionnaires
Week 0 (baseline)
Satiety and eating behavior traits
Time Frame: Week 16 (end of intervention)
Satiety will be also estimated by using a VAS (visual analogue scale) questionnaire and eating behavior traits will be also evaluated with validated questionnaires
Week 16 (end of intervention)
Plasma adipokines and myo-kines
Time Frame: Week 0 (baseline)
CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits
Week 0 (baseline)
Plasma adipokines and myo-kines
Time Frame: Week 16 (end of intervention)
CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits
Week 16 (end of intervention)
Plasma lipids and bioactive lipid mediators
Time Frame: Week 0 (baseline)
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry).
Week 0 (baseline)
Plasma lipids and bioactive lipid mediators
Time Frame: Week 16 (end of intervention)
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry).
Week 16 (end of intervention)
Adipose tissue gene profiling
Time Frame: Week 0 (baseline)
A biopsy (2 g) of subcutaneous abdominal periumbilical area adipose tissue will be obtained by liposuction under local anesthesia. RNA expression will be measured by RNA-seq or GeneChip Human Gene 2.1 ST Array (Affymetrix).
Week 0 (baseline)
Adipose tissue gene profiling
Time Frame: Week 16 (end of intervention)
A biopsy (2 g) of subcutaneous abdominal periumbilical area adipose tissue will be obtained by liposuction under local anesthesia. RNA expression will be measured by RNA-seq or GeneChip Human Gene 2.1 ST Array (Affymetrix).
Week 16 (end of intervention)
Adipose tissue miRNA profiling
Time Frame: Week 0 (baseline)
MiRNA expression will be measured by RNA-seq or GeneChip miRNA 4.0 Array (Affymetrix) in subcutaneous abdominal adipose tissue biopsies.
Week 0 (baseline)
Adipose tissue miRNA profiling
Time Frame: Week 16 (end of intervention)
MiRNA expression will be measured by RNA-seq or GeneChip miRNA 4.0 Array (Affymetrix) in subcutaneous abdominal adipose tissue biopsies.
Week 16 (end of intervention)
Bioactive lipid mediators involved in inflammation in adipose tissue
Time Frame: Week 0 (baseline)
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS
Week 0 (baseline)
Bioactive lipid mediators involved in inflammation in adipose tissue
Time Frame: Week 16 (end of intervention)
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS
Week 16 (end of intervention)
Determination of telomeres length
Time Frame: Week 0 (baseline)
Telomeres length will be measured in genomic DNA extracted from human peripheral blood and adipose tissue samples with a real-time quantitative PCR (polymerase chain reaction) approach.
Week 0 (baseline)
Determination of telomeres length
Time Frame: Week 16 (end of intervention)
Telomeres length will be measured in genomic DNA extracted from human peripheral blood and adipose tissue samples with a real-time quantitative PCR (polymerase chain reaction) approach.
Week 16 (end of intervention)
Characterization of gut microbiota
Time Frame: Week 0 (baseline)
Feces will collected and gut microbiota profiling will be carried out by high-throughput 16S (Svedberg units) rDNA (ribosomal deoxyribonucleic acid) amplicon sequencing approach.
Week 0 (baseline)
Characterization of gut microbiota
Time Frame: Week 16 (end of intervention)
Feces will collected and gut microbiota profiling will be carried out by high-throughput 16S (Svedberg units) rDNA (ribosomal deoxyribonucleic acid) amplicon sequencing approach.
Week 16 (end of intervention)
Urine metabolomic profile
Time Frame: Week 0 (baseline)
Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach.
Week 0 (baseline)
Urine metabolomic profile
Time Frame: Week 16 (end of intervention)
Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach.
Week 16 (end of intervention)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Maria J Moreno-Aliaga, PhD, University of Navarra
  • Principal Investigator: Silvia Lorente-Cebrián, PhD, University of Navarra

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 21, 2017

Primary Completion (Actual)

June 13, 2019

Study Completion (Actual)

June 13, 2019

Study Registration Dates

First Submitted

August 7, 2017

First Submitted That Met QC Criteria

October 2, 2017

First Posted (Actual)

October 3, 2017

Study Record Updates

Last Update Posted (Actual)

November 30, 2020

Last Update Submitted That Met QC Criteria

November 26, 2020

Last Verified

March 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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