Marja A Heiskanen1, Sanna M Honkala1, Jaakko Hentilä1, Ronja Ojala1, Riikka Lautamäki2, Kalle Koskensalo3, Martin S Lietzén1, Virva Saunavaara1,3, Jani Saunavaara3, Mika Helmiö4, Eliisa Löyttyniemi5, Lauri Nummenmaa1,6, Maria C Collado7,8, Tarja Malm9, Leo Lahti10, Kirsi H Pietiläinen11,12, Jaakko Kaprio13, Juha O Rinne1,14, Jarna C Hannukainen15. 1. Turku PET Centre, University of Turku, P.O. Box 52, FIN-20521, Turku, Finland. 2. Heart Centre, Turku University Hospital, Turku, Finland. 3. Department of Medical Physics, Turku University Hospital, Turku, Finland. 4. Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland. 5. Department of Biostatistics, University of Turku, Turku, Finland. 6. Department of Psychology, University of Turku, Turku, Finland. 7. Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Valencia, Spain. 8. Functional Food Forum, University of Turku, Turku, Finland. 9. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. 10. Department of Future Technologies, University of Turku, Turku, Finland. 11. Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 12. Abdominal Center, Obesity Center, Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. 13. Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland. 14. Turku PET Centre, Turku University Hospital, Turku, Finland. 15. Turku PET Centre, University of Turku, P.O. Box 52, FIN-20521, Turku, Finland. jhannukainen@gmail.com.
Abstract
BACKGROUND: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk. METHODS: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983-1987, 1975-1979, and 1945-1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength. DISCUSSION: This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03730610 . Prospectively registered 5 November 2018.
BACKGROUND:Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk. METHODS: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983-1987, 1975-1979, and 1945-1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength. DISCUSSION: This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03730610 . Prospectively registered 5 November 2018.
Authors: Claude Bouchard; Ligia M Antunes-Correa; Euan A Ashley; Nina Franklin; Paul M Hwang; C Mikael Mattsson; Carlos E Negrao; Shane A Phillips; Mark A Sarzynski; Ping-Yuan Wang; Matthew T Wheeler Journal: Prog Cardiovasc Dis Date: 2014-08-13 Impact factor: 8.194
Authors: Laura E Parton; Chian Ping Ye; Roberto Coppari; Pablo J Enriori; Brian Choi; Chen-Yu Zhang; Chun Xu; Claudia R Vianna; Nina Balthasar; Charlotte E Lee; Joel K Elmquist; Michael A Cowley; Bradford B Lowell Journal: Nature Date: 2007-08-29 Impact factor: 49.962
Authors: Jennifer D Deem; Kenjiro Muta; Jarrad M Scarlett; Gregory J Morton; Michael W Schwartz Journal: Diabetes Date: 2017-06-11 Impact factor: 9.461