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

Obesity Clinical Trial

— OBELEX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03300388
• Other study ID #: OBELEX
• Status: Completed
• Phase: N/A
• Start date: August 21, 2017
• Est. completion date: June 13, 2019

Study information

• Verified date: March 2017
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: June 13, 2019
• Est. primary completion date: June 13, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 55 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Inflammation
• Obesity

Intervention

Dietary Supplement:
• Omega-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.
• Placebo (olive oil)
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.

Other:
• Resistance training
Double-blind randomized placebo-controlled intervention with DHA-rich dietary supplement with or without resistance training program for 16 weeks.

Locations

Country	Name	City	State
Spain	Department of Nutrition, Food Science and Physiology. Centre for Nutrition Research.	Pamplona	Navarra

Sponsors (4)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra	Centro de Estudios, Investigación y Medicina del Deporte, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Ministerio de Economía y Competitividad, Spain

Country where clinical trial is conducted

Spain, 

References & Publications (21)

González-Muniesa P, Marrades MP, Martínez JA, Moreno-Aliaga MJ. Differential proinflammatory and oxidative stress response and vulnerability to metabolic syndrome in habitual high-fat young male consumers putatively predisposed by their genetic background. Int J Mol Sci. 2013 Aug 22;14(9):17238-55. doi: 10.3390/ijms140917238. — View Citation

Huerta AE, Navas-Carretero S, Prieto-Hontoria PL, Martínez JA, Moreno-Aliaga MJ. Effects of a-lipoic acid and eicosapentaenoic acid in overweight and obese women during weight loss. Obesity (Silver Spring). 2015 Feb;23(2):313-21. doi: 10.1002/oby.20966. Epub 2014 Dec 31. — View Citation

Huerta AE, Prieto-Hontoria PL, Fernández-Galilea M, Escoté X, Martínez JA, Moreno-Aliaga MJ. Effects of dietary supplementation with EPA and/or a-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet. Biofactors. 2017 Jan 2;43(1):117-131. doi: 10.1002/biof.1317. Epub 2016 Aug 10. — View Citation

Huerta AE, Prieto-Hontoria PL, Fernández-Galilea M, Sáinz N, Cuervo M, Martínez JA, Moreno-Aliaga MJ. Circulating irisin and glucose metabolism in overweight/obese women: effects of a-lipoic acid and eicosapentaenoic acid. J Physiol Biochem. 2015 Sep;71(3):547-58. doi: 10.1007/s13105-015-0400-5. Epub 2015 Mar 28. — View Citation

Huerta AE, Prieto-Hontoria PL, Sáinz N, Martínez JA, Moreno-Aliaga MJ. Supplementation with a-Lipoic Acid Alone or in Combination with Eicosapentaenoic Acid Modulates the Inflammatory Status of Healthy Overweight or Obese Women Consuming an Energy-Restricted Diet. J Nutr. 2015 Apr 1;146(4):889S-896S. doi: 10.3945/jn.115.224105. — View Citation

Laiglesia LM, Lorente-Cebrián S, Prieto-Hontoria PL, Fernández-Galilea M, Ribeiro SM, Sáinz N, Martínez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects. J Nutr Biochem. 2016 Nov;37:76-82. doi: 10.1016/j.jnutbio.2016.07.019. Epub 2016 Aug 26. — View Citation

López-Yoldi M, Stanhope KL, Garaulet M, Chen XG, Marcos-Gómez B, Carrasco-Benso MP, Santa Maria EM, Escoté X, Lee V, Nunez MV, Medici V, Martínez-Ansó E, Sáinz N, Huerta AE, Laiglesia LM, Prieto J, Martínez JA, Bustos M, Havel PJ, Moreno-Aliaga MJ. Role of cardiotrophin-1 in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24-h circulating CT-1 profiles in normal-weight and overweight/obese subjects. FASEB J. 2017 Apr;31(4):1639-1649. doi: 10.1096/fj.201600396RR. Epub 2017 Jan 17. — View Citation

Lorente-Cebrián S, Bustos M, Marti A, Fernández-Galilea M, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid inhibits tumour necrosis factor-a-induced lipolysis in murine cultured adipocytes. J Nutr Biochem. 2012 Mar;23(3):218-27. doi: 10.1016/j.jnutbio.2010.11.018. Epub 2011 Apr 14. — View Citation

Lorente-Cebrián S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond). 2009 Aug 14;117(6):243-9. doi: 10.1042/CS20090020. — View Citation

Lorente-Cebrián S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes. Mol Nutr Food Res. 2010 May;54 Suppl 1:S104-11. doi: 10.1002/mnfr.200900522. — View Citation

Lorente-Cebrián S, Costa AG, Navas-Carretero S, Zabala M, Laiglesia LM, Martínez JA, Moreno-Aliaga MJ. An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases. J Physiol Biochem. 2015 Jun;71(2):341-9. doi: 10.1007/s13105-015-0395-y. Epub 2015 Mar 11. Review. — View Citation

Lorente-Cebrián S, Costa AG, Navas-Carretero S, Zabala M, Martínez JA, Moreno-Aliaga MJ. Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: a review of the evidence. J Physiol Biochem. 2013 Sep;69(3):633-51. doi: 10.1007/s13105-013-0265-4. Epub 2013 Jun 22. Review. — View Citation

Mansego ML, Milagro FI, Zulet MÁ, Moreno-Aliaga MJ, Martínez JA. Differential DNA Methylation in Relation to Age and Health Risks of Obesity. Int J Mol Sci. 2015 Jul 24;16(8):16816-32. doi: 10.3390/ijms160816816. — View Citation

Marrades MP, González-Muniesa P, Arteta D, Martínez JA, Moreno-Aliaga MJ. Orchestrated downregulation of genes involved in oxidative metabolic pathways in obese vs. lean high-fat young male consumers. J Physiol Biochem. 2011 Mar;67(1):15-26. doi: 10.1007/s13105-010-0044-4. Epub 2010 Sep 30. — View Citation

Marrades MP, González-Muniesa P, Martínez JA, Moreno-Aliaga MJ. A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity. Obes Facts. 2010 Oct;3(5):312-8. doi: 10.1159/000321451. Epub 2010 Oct 15. — View Citation

Martínez-Fernández L, González-Muniesa P, Laiglesia LM, Sáinz N, Prieto-Hontoria PL, Escoté X, Odriozola L, Corrales FJ, Arbones-Mainar JM, Martínez JA, Moreno-Aliaga MJ. Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet-induced obese mice. FASEB J. 2017 May;31(5):2135-2145. doi: 10.1096/fj.201600859R. Epub 2017 Feb 10. — View Citation

Martínez-Fernández L, Laiglesia LM, Huerta AE, Martínez JA, Moreno-Aliaga MJ. Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome. Prostaglandins Other Lipid Mediat. 2015 Sep;121(Pt A):24-41. doi: 10.1016/j.prostaglandins.2015.07.003. Epub 2015 Jul 26. Review. — View Citation

Milagro FI, Moreno-Aliaga MJ, Martinez JA. FTO Obesity Variant and Adipocyte Browning in Humans. N Engl J Med. 2016 Jan 14;374(2):190-1. doi: 10.1056/NEJMc1513316. — View Citation

Moreno-Aliaga MJ, Lorente-Cebrián S, Martínez JA. Regulation of adipokine secretion by n-3 fatty acids. Proc Nutr Soc. 2010 Aug;69(3):324-32. doi: 10.1017/S0029665110001801. Epub 2010 Jun 14. Review. — View Citation

Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Marti A, Martínez JA, Moreno-Aliaga MJ. Down-regulation in muscle and liver lipogenic genes: EPA ethyl ester treatment in lean and overweight (high-fat-fed) rats. J Nutr Biochem. 2009 Sep;20(9):705-14. doi: 10.1016/j.jnutbio.2008.06.013. Epub 2008 Sep 30. — View Citation

Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, López-Yoldi M, Sinal CJ, Martínez JA, Moreno-Aliaga MJ. Effects of alpha-lipoic acid on chemerin secretion in 3T3-L1 and human adipocytes. Biochim Biophys Acta. 2016 Mar;1861(3):260-8. doi: 10.1016/j.bbalip.2015.12.011. Epub 2015 Dec 22. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fat mass reduction	Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA).	Week 0 (baseline)
Primary	Fat mass reduction	Evaluation of body fat mass changes induced by the different interventions, analyzed by Dual X-ray Absorptiometry (DXA).	Week 16 (end of intervention)
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 0 (baseline)
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 2
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 4
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 6
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 8
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 10
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 12
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 14
Secondary	Evolution of fat mass reduction	Evaluation of body fat mass changes induced by the different interventions analyzed by bioimpedance.	Week 16 (end of intervention)
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 0 (baseline)
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 2
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 4
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 6
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 8
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 10
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 12
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 14
Secondary	Weight loss	Changes in body weight will be measured by a body weight scale to the nearest 0.1 kg	Week 16 (end of intervention)
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 0 (baseline)
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 2
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 4
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 6
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 8
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 10
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 12
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 14
Secondary	Evolution of body composition	Evaluation of fat-free mass changes will be analyzed by bioimpedance.	Week 16 (end of intervention)
Secondary	Hip circumference	Hip circumference will be measured with a measuring tape.	Week 0 (baseline)
Secondary	Hip circumference	Hip circumference will be measured with a measuring tape.	Week 8
Secondary	Hip circumference	Hip circumference will be measured with a measuring tape.	Week 16 (end of intervention)
Secondary	Neck circumference	Neck circumference will be measured with a measuring tape.	Week 0 (baseline)
Secondary	Neck circumference	Neck circumference will be measured with a measuring tape.	Week 8
Secondary	Neck circumference	Neck circumference will be measured with a measuring tape.	Week 16 (end of intervention)
Secondary	Waist circumference	Waist circumference will be measured with a measuring tape.	Week 0 (baseline)
Secondary	Waist circumference	Waist circumference will be measured with a measuring tape.	Week 8
Secondary	Waist circumference	Waist circumference will be measured with a measuring tape.	Week 16 (end of intervention)
Secondary	Abdomen circumference	Abdomen circumference will be measured with a measuring tape.	Week 0 (baseline)
Secondary	Abdomen circumference	Abdomen circumference will be measured with a measuring tape.	Week 8
Secondary	Abdomen circumference	Abdomen circumference will be measured with a measuring tape.	Week 16 (end of intervention)
Secondary	Arm circumference	Arm circumference will be measured with a measuring tape.	Week 0 (baseline)
Secondary	Arm circumference	Arm circumference will be measured with a measuring tape.	Week 8
Secondary	Arm circumference	Arm circumference will be measured with a measuring tape.	Week 16 (end of intervention)
Secondary	Midthigh circumference	Midthigh circumference will be measured with a measuring tape.	Week 0 (baseline)
Secondary	Midthigh circumference	Midthigh circumference will be measured with a measuring tape.	Week 8
Secondary	Midthigh circumference	Midthigh circumference will be measured with a measuring tape.	Week 16 (end of intervention)
Secondary	Midcalf circumference	Midcalf circumference will be measured with a measuring tape.	Week 0 (baseline)
Secondary	Midcalf circumference	Midcalf circumference will be measured with a measuring tape.	Week 8
Secondary	Midcalf circumference	Midcalf circumference will be measured with a measuring tape.	Week 16 (end of intervention)
Secondary	Triceps skinfold	Triceps skinfold will be measured with a caliper.	Week 0 (baseline)
Secondary	Triceps skinfold	Triceps skinfold will be measured with a caliper.	Week 8
Secondary	Triceps skinfold	Triceps skinfold will be measured with a caliper.	Week 16 (end of intervention)
Secondary	Thigh skinfold	Thigh skinfold will be measured with a caliper.	Week 0 (baseline)
Secondary	Thigh skinfold	Thigh skinfold will be measured with a caliper.	Week 8
Secondary	Thigh skinfold	Thigh skinfold will be measured with a caliper.	Week 16 (end of intervention)
Secondary	Medial calf skinfold	Medial calf skinfold will be measured with a caliper.	Week 0 (baseline)
Secondary	Medial calf skinfold	Medial calf skinfold will be measured with a caliper.	Week 8
Secondary	Medial calf skinfold	Medial calf skinfold will be measured with a caliper.	Week 16 (end of intervention)
Secondary	Blood pressure	Systolic and diastolic blood pressure will be measured with a tensiometer.	Week 0 (baseline)
Secondary	Blood pressure	Systolic and diastolic blood pressure will be measured with a tensiometer.	Week 8
Secondary	Blood pressure	Systolic and diastolic blood pressure will be measured with a tensiometer.	Week 16 (end of intervention)
Secondary	Serum glucose	Fasting serum glucose will be measured after overnight fast.	Week 0 (baseline)
Secondary	Serum glucose	Fasting serum glucose will be measured after overnight fast.	Week 16 (end of intervention)
Secondary	Serum insulin	Fasting serum insulin will be measured after overnight fast.	Week 0 (baseline)
Secondary	Serum insulin	Fasting serum insulin will be measured after overnight fast.	Week 16 (end of intervention)
Secondary	Oral Glucose Tolerance Test	Oral Glucose Tolerance Test will be carried out after overnight fast.	Week 0 (baseline)
Secondary	Oral Glucose Tolerance Test	Oral Glucose Tolerance Test will be carried out after overnight fast.	Week 16 (end of intervention)
Secondary	Lipid metabolism biomarkers	Serum free fatty acids, triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations will be measured after an overnight fast.	Week 0 (baseline)
Secondary	Lipid metabolism biomarkers	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)
Secondary	Ketone bodies	Ketone bodies concentrations will be measured after an overnight fast.	Week 0 (baseline)
Secondary	Ketone bodies	Ketone bodies concentrations will be measured after an overnight fast.	Week 16 (end of intervention)
Secondary	Thyroid function (body metabolism)	TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits	Week 0 (baseline)
Secondary	Thyroid function (body metabolism)	TSH (thyroid-stimulating hormone), T3 and T4 hormones will be evaluated with ELISA kits	Week 16 (end of intervention)
Secondary	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	Week 0 (baseline)
Secondary	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	Week 16 (end of intervention)
Secondary	Inflammation biomarkers	TNF-a (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)
Secondary	Inflammation biomarkers	TNF-a (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)
Secondary	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	Week 0 (baseline)
Secondary	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	Week 16 (end of intervention)
Secondary	Plasma adipokines and myo-kines	CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits	Week 0 (baseline)
Secondary	Plasma adipokines and myo-kines	CT-1, irisin, FGF21 (fibroblast growth factor 21) and meteorin-like will be measured using ELISA kits	Week 16 (end of intervention)
Secondary	Plasma lipids and bioactive lipid mediators	Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry).	Week 0 (baseline)
Secondary	Plasma lipids and bioactive lipid mediators	Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS (high pressure liquid chromatography-mass spectrometry).	Week 16 (end of intervention)
Secondary	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).	Week 0 (baseline)
Secondary	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).	Week 16 (end of intervention)
Secondary	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.	Week 0 (baseline)
Secondary	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.	Week 16 (end of intervention)
Secondary	Bioactive lipid mediators involved in inflammation in adipose tissue	Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS	Week 0 (baseline)
Secondary	Bioactive lipid mediators involved in inflammation in adipose tissue	Lipidomic profile will be measured using targeted metabolomic-lipidomics by HPLC-MS	Week 16 (end of intervention)
Secondary	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.	Week 0 (baseline)
Secondary	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.	Week 16 (end of intervention)
Secondary	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.	Week 0 (baseline)
Secondary	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.	Week 16 (end of intervention)
Secondary	Urine metabolomic profile	Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach.	Week 0 (baseline)
Secondary	Urine metabolomic profile	Urine will be collected and urinary metabolomic profile will be also evaluated by a HPLC-MS approach.	Week 16 (end of intervention)

External Links

•   Centre for Nutrition Research. University of Navarra
•   Department of Nutrition, Food Science and Physiology. University of Navarra