Obesity, Inflammation and Aging: Effects of Physical Exercise and Omega-3 Fatty Acids.
- Conditions
- ObesityAgingInflammation
- Interventions
- Dietary Supplement: Placebo (olive oil)Dietary Supplement: Omega-3 (DHA-rich dietary supplement)Other: Resistance training
- Registration Number
- NCT03300388
- Lead Sponsor
- Clinica Universidad de Navarra, Universidad de Navarra
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 85
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Omega-3 + Resistance Training 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. Control Placebo (olive oil) Dietary advice for a healthy diet supplemented with placebo (olive oil). Resistance Training Placebo (olive oil) Dietary advice for a healthy diet supplemented with placebo (olive oil) and moderate resistance training program. Omega-3 + Resistance Training Omega-3 (DHA-rich dietary supplement) 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. Omega-3 Omega-3 (DHA-rich dietary supplement) Dietary advice for a healthy diet supplemented with DHA-rich dietary supplement (providing 1.650 mg/day of DHA). Resistance Training Resistance training Dietary advice for a healthy diet supplemented with placebo (olive oil) and moderate resistance training program.
- Primary Outcome Measures
Name Time Method Fat mass reduction Week 16 (end of intervention) Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA).
- Secondary Outcome Measures
Name Time Method Urine metabolomic profile Week 16 (end of intervention) Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach.
Evolution of fat mass reduction Week 16 (end of intervention) Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.
Midcalf circumference Week 16 (end of intervention) Midcalf circumference will be measured with a measuring tape.
Evolution of body composition Week 16 (end of intervention) Evaluation of fat-free mass changes will be analyzed by bioimpedance.
Neck circumference Week 16 (end of intervention) Neck circumference will be measured with a measuring tape.
Abdomen circumference Week 16 (end of intervention) Abdomen circumference will be measured with a measuring tape.
Adipose tissue miRNA profiling 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.
Determination of telomeres length 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.
Hip circumference Week 16 (end of intervention) Hip circumference will be measured with a measuring tape.
Waist circumference Week 16 (end of intervention) Waist circumference will be measured with a measuring tape.
Arm circumference Week 16 (end of intervention) Arm circumference will be measured with a measuring tape.
Midthigh circumference Week 16 (end of intervention) Midthigh circumference will be measured with a measuring tape.
Thigh skinfold Week 16 (end of intervention) Thigh skinfold will be measured with a caliper.
Blood pressure Week 16 (end of intervention) Systolic and diastolic blood pressure will be measured with a tensiometer.
Adipose tissue gene profiling 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).
Characterization of gut microbiota 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.
Weight loss Week 16 (end of intervention) Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg
Medial calf skinfold Week 16 (end of intervention) Medial calf skinfold will be measured with a caliper.
Lipid metabolism biomarkers 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.
Thyroid function (body metabolism) Week 16 (end of intervention) TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits
Bioactive lipid mediators involved in inflammation in adipose tissue Week 16 (end of intervention) Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS
Serum insulin Week 16 (end of intervention) Fasting serum insulin will be measured after overnight fast.
Oral Glucose Tolerance Test Week 16 (end of intervention) Oral Glucose Tolerance Test will be carried out after overnight fast.
Cardiovascular risk biomarkers 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
Plasma adipokines and myo-kines Week 16 (end of intervention) CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits
Plasma lipids and bioactive lipid mediators Week 16 (end of intervention) Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry).
Triceps skinfold Week 16 (end of intervention) Triceps skinfold will be measured with a caliper.
Ketone bodies Week 16 (end of intervention) Ketone bodies concentrations will be measured after an overnight fast.
Inflammation biomarkers 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
Satiety and eating behavior traits 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
Serum glucose Week 16 (end of intervention) Fasting serum glucose will be measured after overnight fast.
Trial Locations
- Locations (1)
Department of Nutrition, Food Science and Physiology. Centre for Nutrition Research.
🇪🇸Pamplona, Navarra, Spain