Context Exercise training improves bone mineral density, but little is known about the effects of training on bone marrow (BM) metabolism. BM insulin sensitivity has been suggested to play an important role in bone health and whole-body insulin sensitivity. Objective To study the effects of exercise training on BM metabolism. Design Randomized controlled trial Setting Clinical research center Participants Sedentary healthy (n=28, 40-55 years, all males) and insulin resistant subjects (IR) (n=26, 43-55 years, males/females 16/10) Intervention Two weeks of sprint interval training or moderate-intensity continuous training Main outcome measures We measured femoral, lumbar and thoracic BM insulin-stimulated glucose uptake (GU) and fasting free fatty acid uptake (FFAU) using positron-emission tomography and bone turnover markers from plasma. Results At baseline, GU was highest in lumbar, followed by thoracic and lowest in femoral BM (all p<0.0001). FFAU was higher in lumbar and thoracic than femoral BM (both p<0.0001). BM FFAU and femoral BM GU were higher in healthy compared to IR men and in females compared to males (all p<0.05). Training increased femoral BM GU similarly in all groups and decreased lumbar BM FFAU in males (all p<0.05). Osteocalcin and PINP were lower in IR than healthy men and correlated positively with femoral BM GU and glycemic status (all p<0.05). Conclusions BM metabolism differs regarding anatomical location. Short-term training improves BM GU and FFAU in healthy and IR subjects. Bone turnover rate is decreased in insulin resistance and associates positively with BM metabolism and glycemic control.

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.