Mitochondrial Energy Metabolism in Obese Women

Obesity Clinical Trial

Official title:

Mitochondrial Energy Metabolism in Obese Women Undergoing Concurrent Physical Training

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03119350
• Other study ID #: Process HCRP: 1.387.040/2016
• Status: Completed
• Phase: N/A
• Start date: April 1, 2016
• Est. completion date: September 15, 2016

Study information

• Verified date: April 2019
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Considering that the failure of the treatment of obesity is justified by the multifactorial pathophysiology of this morbidity, the present project has the following hypotheses:

1. The occurrence of obesity is due to the derange,ent of mitochondrial energy metabolism ;

2. The unbalance is therapeutically modified through physical training ;

3. Obesity courses with the break-down in energy metabolism mitochondrial disease associated with systemic inflammatory characteristics that can be corrected through a combined long-term physical training program.

This study have as objective : to analyse changes in mitochondrial function, inflammatory profile, oxidative stress and energy metabolism caused by concurrent physical training in obese women.

Description:

Specific objectives:

Body composition by deuterium oxide; Metabolic rate of resting and oxidation of substrates by indirect calorimetry; Proinflammatory cytokines Anti-inflammatory cytokines Oxidative Stress: Malondialdehyde, Superoxide Dismutase, Glutathione-Peroxidase; Fatty acids: ceramide and palmitate; Mitochondrial respiration and citrate synthase enzyme; Quantify and qualify: mitochondrial number, endoplasmic reticulum structure, adipose cell size; Gene expression, quantify by microscopy and analyze the protein by western blot.

The study began with 20 women, however, there was withdrawal of 6, ending with 14 women.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: September 15, 2016
• Est. primary completion date: July 1, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• This study included women with obesity (BMI of 30 to 40 kg / m²), sedentary, with no associated comorbidity, convenience sample

Exclusion Criteria:

• Women who have undergone bariatric surgery, menopause, cancer or any metabolic disease, smokers, alcoholics, who are in use of drugs that act directly on the metabolism and that have medical impediment to the practice of physical exercise.

Related Conditions & MeSH terms

• Metabolic Diseases
• Metabolism Disorder
• Mitochondrial Alteration
• Obesity
• Physical Activity

Intervention

Other:
• Physical Training
Intervention with concurrent physical training: strength and aerobic exercises in the same session. Duration: 2 weeks of adaptation to physical exercise, 8 weeks of training. Frequency: 3 times a week. Time: 55 minutes each session. Intensity: 75 to 90% of maximum heart rate.

Locations

Country	Name	City	State
Brazil	Camila Fernanda Cunha Brandão	Ribeirao Preto	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (27)

BROWN, L.E.; WEIR, J.P.; ASEP procedures recommendation i: accurate assessment of muscular strength and power, Journal of Exercise Physiology, v. 4, n. 3, p. 1-21, 2001.

Burgomaster KA, Howarth KR, Phillips SM, Rakobowchuk M, Macdonald MJ, McGee SL, Gibala MJ. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J Physiol. 2008 Jan 1;586(1):151-60. Epub 2007 Nov 8. — View Citation

Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156-9. — View Citation

Colégio Americano de Medicina Esportiva, CAME. Guia para Teste de Esforço e Prescrição de Exercício. 3º Edição, Medsi, Rio de janeiro, RJ, p.25, 1987.

Crump C, Sundquist J, Winkleby MA, Sundquist K. Interactive effects of obesity and physical fitness on risk of ischemic heart disease. Int J Obes (Lond). 2017 Feb;41(2):255-261. doi: 10.1038/ijo.2016.209. Epub 2016 Nov 21. — View Citation

Curtis JM, Grimsrud PA, Wright WS, Xu X, Foncea RE, Graham DW, Brestoff JR, Wiczer BM, Ilkayeva O, Cianflone K, Muoio DE, Arriaga EA, Bernlohr DA. Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction. Diabetes. 2010 May;59(5):1132-42. doi: 10.2337/db09-1105. Epub 2010 Feb 11. — View Citation

Daussin FN, Zoll J, Dufour SP, Ponsot E, Lonsdorfer-Wolf E, Doutreleau S, Mettauer B, Piquard F, Geny B, Richard R. Effect of interval versus continuous training on cardiorespiratory and mitochondrial functions: relationship to aerobic performance improvements in sedentary subjects. Am J Physiol Regul Integr Comp Physiol. 2008 Jul;295(1):R264-72. doi: 10.1152/ajpregu.00875.2007. Epub 2008 Apr 16. — View Citation

EIGENTLER, A.; DRAXL, A.; et al. Laboratory Protocol: Citrate synthase a mitochondrial marker enzyme. Mitochondrial Physiology Network, v. 17.04, n. 3, p. 1-11, 2015.

Fernström M, Bakkman L, Loogna P, Rooyackers O, Svensson M, Jakobsson T, Brandt L, Lagerros YT. Improved Muscle Mitochondrial Capacity Following Gastric Bypass Surgery in Obese Subjects. Obes Surg. 2016 Jul;26(7):1391-7. doi: 10.1007/s11695-015-1932-z. — View Citation

Ferreira FC, Bertucci DR, Barbosa MR, Nunes JE, Botero JP, Rodrigues MF, Shiguemoto GE, Santoro V, Verzola AC, Nonaka RO, Verzola RM, Baldissera V, Perez SE. Circuit resistance training in women with normal weight obesity syndrome: body composition, cardiometabolic and echocardiographic parameters, and cardiovascular and skeletal muscle fitness. J Sports Med Phys Fitness. 2017 Jul-Aug;57(7-8):1033-1044. doi: 10.23736/S0022-4707.16.06391-X. Epub 2016 Jul 6. — View Citation

FETT, C.A.; FETT, W.C.R.; MARCHINI, J.S. Fitness Level of Overweight/Obese Women After 08 Weeks of Aerobic or Mixed Metabolism Exercises. Revista Brasileira de Cineantropometria & Desempenho Humano, v. 11, p. 261-266, 2009.

Foster C. Monitoring training in athletes with reference to overtraining syndrome. Med Sci Sports Exerc. 1998 Jul;30(7):1164-8. — View Citation

Frayn KN. Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol Respir Environ Exerc Physiol. 1983 Aug;55(2):628-34. — View Citation

Grimble GK, West MF, Acuti AB, Rees RG, Hunjan MK, Webster JD, Frost PG, Silk DB. Assessment of an automated chemiluminescence nitrogen analyzer for routine use in clinical nutrition. JPEN J Parenter Enteral Nutr. 1988 Jan-Feb;12(1):100-6. — View Citation

Heilbronn LK, Gan SK, Turner N, Campbell LV, Chisholm DJ. Markers of mitochondrial biogenesis and metabolism are lower in overweight and obese insulin-resistant subjects. J Clin Endocrinol Metab. 2007 Apr;92(4):1467-73. Epub 2007 Jan 23. — View Citation

Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, Kim SY, Kim MS, Kim SW, Park IS, Youn JH, Lee KU. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes. 2007 Dec;56(12):2973-81. Epub 2007 Sep 7. — View Citation

Kong Z, Sun S, Liu M, Shi Q. Short-Term High-Intensity Interval Training on Body Composition and Blood Glucose in Overweight and Obese Young Women. J Diabetes Res. 2016;2016:4073618. Epub 2016 Sep 28. — View Citation

Kraunsøe R, Boushel R, Hansen CN, Schjerling P, Qvortrup K, Støckel M, Mikines KJ, Dela F. Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity. J Physiol. 2010 Jun 15;588(Pt 12):2023-32. doi: 10.1113/jphysiol.2009.184754. Epub 2010 Apr 26. Erratum in: J Physiol. 2010 Oct 15; 588(Pt 20):4055. — View Citation

Lepage G, Roy CC. Improved recovery of fatty acid through direct transesterification without prior extraction or purification. J Lipid Res. 1984 Dec 1;25(12):1391-6. — View Citation

Medbø JI, Mamen A, Holt Olsen O, Evertsen F. Examination of four different instruments for measuring blood lactate concentration. Scand J Clin Lab Invest. 2000 Aug;60(5):367-80. — View Citation

Perry CG, Lally J, Holloway GP, Heigenhauser GJ, Bonen A, Spriet LL. Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol. 2010 Dec 1;588(Pt 23):4795-810. doi: 10.1113/jphysiol.2010.199448. Epub 2010 Oct 4. — View Citation

Pfrimer K, Moriguti JC, Lima NK, Marchini JS, Ferriolli E. Bioelectrical impedance with different equations versus deuterium oxide dilution method for the inference of body composition in healthy older persons. J Nutr Health Aging. 2012 Feb;16(2):124-7. — View Citation

POLLOCK, M.L.; WILMORE, J.H.; FOX III, S.M. Exercícios na Saúde e na Doença - Avaliação e prescrição para prevenção e reabilitação. Rio de Janeiro: 1986.

Singh SJ, Morgan MD, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax. 1992 Dec;47(12):1019-24. — View Citation

Tan S, Wang J, Cao L, Guo Z, Wang Y. Positive effect of exercise training at maximal fat oxidation intensity on body composition and lipid metabolism in overweight middle-aged women. Clin Physiol Funct Imaging. 2016 May;36(3):225-30. doi: 10.1111/cpf.12217. Epub 2014 Nov 19. — View Citation

WEIR JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949 Aug;109(1-2):1-9. — View Citation

Yin X, Lanza IR, Swain JM, Sarr MG, Nair KS, Jensen MD. Adipocyte mitochondrial function is reduced in human obesity independent of fat cell size. J Clin Endocrinol Metab. 2014 Feb;99(2):E209-16. doi: 10.1210/jc.2013-3042. Epub 2013 Nov 25. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes Body weight	Body weight was measured by digital balance before and after the intervention	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes Body composition	The change in body composition through deuterium oxide was evaluated.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes White adipose tissue biopsy	A subcutaneous tissue sample was collected for analysis of: mitochondrial respiration, citrate synthase enzyme, gene expression (UCP1, 2 and 3).	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes Indirect calorimetry	With a gas analyzer (indirect calorimeter), we evaluated the metabolic rate and rest (REE) and oxidation of substrates (Lipids and carbohydrates).	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes in fatty acids	Collected in lithium heparin tubes, they were centrifuged.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes oxidative stress	Collected in lithium heparin tubes, they were centrifuged.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes inflammatory cytokines	Collected in lithium heparin tubes, they were centrifuged.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes in total cholesterol	Collected in lithium heparin tubes, they were centrifuged.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes Physical Performance	Based on the Shuttle Walking Test adaptation.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes in Determination of Lactate	Blood samples were collected by manual puncture of the earlobe in previously calibrated and heparinized capillary tubes, stored in eppendorf with sodium fluoride. Analyzed by electrochemical lactate analyser.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes Food intake	Food registry of 3 days, the quantification of the daily intake of nutrients will still be made using software.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes Nitrogen Balance	Through the collection of urine of 24 hours the dosage of urinary nitrogen will be made by the chemiluminescence method for determination of protein nitrogen.	Two times: (1) First day and (2) 10 weeks after adaptation and intervention
Primary	Changes Telomere length	peripheral blood in ethylenediaminetetraacetic acid tubes and genomic DNA was automatically extracted from Peripheral Blood Mononuclear Cell. The relative quantification of Telomere length was determined using the telomere to single copy gene ratio by Quantitative Polymerase Chain Reaction (qPCR).	Two times: (1) First day and (2) 10 weeks after adaptation and intervention