Aging, Inflammation, Obesity
Conditions
Keywords
Insulin resistance, Exercise, Omega-3 fatty acids, Adipose tissue
Brief summary
Dysfunction of adipose tissue in obesity, inflammation and aging: mechanisms and effects of physical exercise and omega-3 fatty acids.
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.
Interventions
DIETARY_SUPPLEMENTOmega-3 (DHA-rich dietary supplement)
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
DIETARY_SUPPLEMENTPlacebo (olive oil)
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
OTHERResistance training
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.
Sponsors
Ministerio de Economía y Competitividad, Spain
Centro de Estudios, Investigación y Medicina del Deporte
Instituto de Investigación Sanitaria de Navarra (IdiSNA)
Clinica Universidad de Navarra, Universidad de Navarra
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fat mass reduction | Week 0 (baseline) | Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight loss | Week 0 (baseline) | Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg |
| Evolution of body composition | Week 0 (baseline) | Evaluation of fat-free mass changes will be analyzed by bioimpedance. |
| Hip circumference | Week 0 (baseline) | Hip circumference will be measured with a measuring tape. |
| Neck circumference | Week 0 (baseline) | Neck circumference will be measured with a measuring tape. |
| Waist circumference | Week 0 (baseline) | Waist circumference will be measured with a measuring tape. |
| Abdomen circumference | Week 0 (baseline) | Abdomen circumference will be measured with a measuring tape. |
| Arm circumference | Week 0 (baseline) | Arm circumference will be measured with a measuring tape. |
| Midthigh circumference | Week 0 (baseline) | Midthigh circumference will be measured with a measuring tape. |
| Midcalf circumference | Week 0 (baseline) | Midcalf circumference will be measured with a measuring tape. |
| Triceps skinfold | Week 0 (baseline) | Triceps skinfold will be measured with a caliper. |
| Thigh skinfold | Week 0 (baseline) | Thigh skinfold will be measured with a caliper. |
| Medial calf skinfold | Week 0 (baseline) | Medial calf skinfold will be measured with a caliper. |
| Blood pressure | Week 0 (baseline) | Systolic and diastolic blood pressure will be measured with a tensiometer. |
| Serum glucose | Week 0 (baseline) | Fasting serum glucose will be measured after overnight fast. |
| Serum insulin | Week 0 (baseline) | Fasting serum insulin will be measured after overnight fast. |
| Evolution of fat mass reduction | Week 0 (baseline) | Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance. |
| Lipid metabolism biomarkers | Week 0 (baseline) | Serum free fatty acids, triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations will be measured after an overnight fast. |
| Ketone bodies | Week 0 (baseline) | Ketone bodies concentrations will be measured after an overnight fast. |
| Thyroid function (body metabolism) | Week 0 (baseline) | TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits |
| Cardiovascular risk biomarkers | 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 |
| Inflammation biomarkers | 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 |
| Satiety and eating behavior traits | 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 |
| Plasma adipokines and myo-kines | Week 0 (baseline) | CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits |
| Plasma lipids and bioactive lipid mediators | Week 0 (baseline) | Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry). |
| Adipose tissue gene profiling | 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). |
| Adipose tissue miRNA profiling | Week 0 (baseline) | MiRNA expression will be measured by RNA-seq or GeneChip miRNA 4.0 Array (Affymetrix) in subcutaneous abdominal adipose tissue biopsies. |
| Bioactive lipid mediators involved in inflammation in adipose tissue | Week 0 (baseline) | Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS |
| Determination of telomeres length | 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. |
| Characterization of gut microbiota | 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. |
| Urine metabolomic profile | Week 0 (baseline) | Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach. |
| Oral Glucose Tolerance Test | Week 0 (baseline) | Oral Glucose Tolerance Test will be carried out after overnight fast. |
Countries
Spain
Outcome results
None listed