Dysfunction of adipose tissue in obesity, inflammation and aging: mechanisms and effects of physical exercise and omega-3 fatty acids.
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
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
85
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.
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
Department of Nutrition, Food Science and Physiology. Centre for Nutrition Research.
Pamplona, Navarre, Spain
Fat mass reduction
Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA).
Time frame: Week 0 (baseline)
Fat mass reduction
Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA).
Time frame: Week 16 (end of intervention)
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 0 (baseline)
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 2
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 4
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 6
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 8
Evolution of fat mass reduction
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Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 10
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 12
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 14
Evolution of fat mass reduction
Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Time frame: Week 16 (end of intervention)
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 0 (baseline)
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 2
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 4
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 6
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 8
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 10
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 12
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 14
Weight loss
Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Time frame: Week 16 (end of intervention)
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 0 (baseline)
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 2
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 4
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 6
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 8
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 10
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 12
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 14
Evolution of body composition
Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Time frame: Week 16 (end of intervention)
Hip circumference
Hip circumference will be measured with a measuring tape.
Time frame: Week 0 (baseline)
Hip circumference
Hip circumference will be measured with a measuring tape.
Time frame: Week 8
Hip circumference
Hip circumference will be measured with a measuring tape.
Time frame: Week 16 (end of intervention)
Neck circumference
Neck circumference will be measured with a measuring tape.
Time frame: Week 0 (baseline)
Neck circumference
Neck circumference will be measured with a measuring tape.
Time frame: Week 8
Neck circumference
Neck circumference will be measured with a measuring tape.
Time frame: Week 16 (end of intervention)
Waist circumference
Waist circumference will be measured with a measuring tape.
Time frame: Week 0 (baseline)
Waist circumference
Waist circumference will be measured with a measuring tape.
Time frame: Week 8
Waist circumference
Waist circumference will be measured with a measuring tape.
Time frame: Week 16 (end of intervention)
Abdomen circumference
Abdomen circumference will be measured with a measuring tape.
Time frame: Week 0 (baseline)
Abdomen circumference
Abdomen circumference will be measured with a measuring tape.
Time frame: Week 8
Abdomen circumference
Abdomen circumference will be measured with a measuring tape.
Time frame: Week 16 (end of intervention)
Arm circumference
Arm circumference will be measured with a measuring tape.
Time frame: Week 0 (baseline)
Arm circumference
Arm circumference will be measured with a measuring tape.
Time frame: Week 8
Arm circumference
Arm circumference will be measured with a measuring tape.
Time frame: Week 16 (end of intervention)
Midthigh circumference
Midthigh circumference will be measured with a measuring tape.
Time frame: Week 0 (baseline)
Midthigh circumference
Midthigh circumference will be measured with a measuring tape.
Time frame: Week 8
Midthigh circumference
Midthigh circumference will be measured with a measuring tape.
Time frame: Week 16 (end of intervention)
Midcalf circumference
Midcalf circumference will be measured with a measuring tape.
Time frame: Week 0 (baseline)
Midcalf circumference
Midcalf circumference will be measured with a measuring tape.
Time frame: Week 8
Midcalf circumference
Midcalf circumference will be measured with a measuring tape.
Time frame: Week 16 (end of intervention)
Triceps skinfold
Triceps skinfold will be measured with a caliper.
Time frame: Week 0 (baseline)
Triceps skinfold
Triceps skinfold will be measured with a caliper.
Time frame: Week 8
Triceps skinfold
Triceps skinfold will be measured with a caliper.
Time frame: Week 16 (end of intervention)
Thigh skinfold
Thigh skinfold will be measured with a caliper.
Time frame: Week 0 (baseline)
Thigh skinfold
Thigh skinfold will be measured with a caliper.
Time frame: Week 8
Thigh skinfold
Thigh skinfold will be measured with a caliper.
Time frame: Week 16 (end of intervention)
Medial calf skinfold
Medial calf skinfold will be measured with a caliper.
Time frame: Week 0 (baseline)
Medial calf skinfold
Medial calf skinfold will be measured with a caliper.
Time frame: Week 8
Medial calf skinfold
Medial calf skinfold will be measured with a caliper.
Time frame: Week 16 (end of intervention)
Blood pressure
Systolic and diastolic blood pressure will be measured with a tensiometer.
Time frame: Week 0 (baseline)
Blood pressure
Systolic and diastolic blood pressure will be measured with a tensiometer.
Time frame: Week 8
Blood pressure
Systolic and diastolic blood pressure will be measured with a tensiometer.
Time frame: Week 16 (end of intervention)
Serum glucose
Fasting serum glucose will be measured after overnight fast.
Time frame: Week 0 (baseline)
Serum glucose
Fasting serum glucose will be measured after overnight fast.
Time frame: Week 16 (end of intervention)
Serum insulin
Fasting serum insulin will be measured after overnight fast.
Time frame: Week 0 (baseline)
Serum insulin
Fasting serum insulin will be measured after overnight fast.
Time frame: Week 16 (end of intervention)
Oral Glucose Tolerance Test
Oral Glucose Tolerance Test will be carried out after overnight fast.
Time frame: Week 0 (baseline)
Oral Glucose Tolerance Test
Oral Glucose Tolerance Test will be carried out after overnight fast.
Time frame: Week 16 (end of intervention)
Lipid metabolism biomarkers
Serum free fatty acids, triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations will be measured after an overnight fast.
Time frame: Week 0 (baseline)
Lipid metabolism biomarkers
Serum free fatty acids, triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations will be measured after an overnight fast.
Time frame: Week 16 (end of intervention)
Ketone bodies
Ketone bodies concentrations will be measured after an overnight fast.
Time frame: Week 0 (baseline)
Ketone bodies
Ketone bodies concentrations will be measured after an overnight fast.
Time frame: Week 16 (end of intervention)
Thyroid function (body metabolism)
TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits
Time frame: Week 0 (baseline)
Thyroid function (body metabolism)
TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits
Time frame: Week 16 (end of intervention)
Cardiovascular risk biomarkers
PAI-1 (plasminogen activator inhibitor-1), ADMA (asymmetric dimethylarginine) and VEGF (vascular endothelial growth factor) will be measured in plasma using ELISA kits
Time frame: Week 0 (baseline)
Cardiovascular risk biomarkers
PAI-1 (plasminogen activator inhibitor-1), ADMA (asymmetric dimethylarginine) and VEGF (vascular endothelial growth factor) will be measured in plasma using ELISA kits
Time frame: Week 16 (end of intervention)
Inflammation biomarkers
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
Time frame: Week 0 (baseline)
Inflammation biomarkers
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
Time frame: Week 16 (end of intervention)
Satiety and eating behavior traits
Satiety will be also estimated by using a VAS (visual analogue scale) questionnaire and eating behavior traits will be also evaluated with validated questionnaires
Time frame: Week 0 (baseline)
Satiety and eating behavior traits
Satiety will be also estimated by using a VAS (visual analogue scale) questionnaire and eating behavior traits will be also evaluated with validated questionnaires
Time frame: Week 16 (end of intervention)
Plasma adipokines and myo-kines
CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits
Time frame: Week 0 (baseline)
Plasma adipokines and myo-kines
CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits
Time frame: Week 16 (end of intervention)
Plasma lipids and bioactive lipid mediators
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry).
Time frame: Week 0 (baseline)
Plasma lipids and bioactive lipid mediators
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry).
Time frame: Week 16 (end of intervention)
Adipose tissue gene profiling
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).
Time frame: Week 0 (baseline)
Adipose tissue gene profiling
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).
Time frame: Week 16 (end of intervention)
Adipose tissue miRNA profiling
MiRNA expression will be measured by RNA-seq or GeneChip miRNA 4.0 Array (Affymetrix) in subcutaneous abdominal adipose tissue biopsies.
Time frame: Week 0 (baseline)
Adipose tissue miRNA profiling
MiRNA expression will be measured by RNA-seq or GeneChip miRNA 4.0 Array (Affymetrix) in subcutaneous abdominal adipose tissue biopsies.
Time frame: Week 16 (end of intervention)
Bioactive lipid mediators involved in inflammation in adipose tissue
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS
Time frame: Week 0 (baseline)
Bioactive lipid mediators involved in inflammation in adipose tissue
Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS
Time frame: Week 16 (end of intervention)
Determination of telomeres length
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.
Time frame: Week 0 (baseline)
Determination of telomeres length
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.
Time frame: Week 16 (end of intervention)
Characterization of gut microbiota
Feces will collected and gut microbiota profiling will be carried out by high-throughput 16S (Svedberg units) rDNA (ribosomal deoxyribonucleic acid) amplicon sequencing approach.
Time frame: Week 0 (baseline)
Characterization of gut microbiota
Feces will collected and gut microbiota profiling will be carried out by high-throughput 16S (Svedberg units) rDNA (ribosomal deoxyribonucleic acid) amplicon sequencing approach.
Time frame: Week 16 (end of intervention)
Urine metabolomic profile
Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach.
Time frame: Week 0 (baseline)
Urine metabolomic profile
Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach.
Time frame: Week 16 (end of intervention)