Publications by authors named "Kari Kalliokoski"

118 Publications

Positron emission tomography study of effects of two pressure-relieving support surfaces on pressure ulcer development.

J Wound Care 2021 Jan;30(1):54-62

Turku PET Centre, Turku University Hospital and University of Turku, Kiinamyllynkatu 4-8, Turku, Finland.

Objective: To study the pathophysiological cascade of pressure ulcer (PU) development consisting of tissue deformation, inflammation and hypoxia.

Method: In this crossover study, deformation was measured with computerised tomography (CT) linked with contact area reflecting immersion and envelopment. Inflammation and hypoxia were measured using subepidermal moisture (SEM), skin temperature and tissue perfusion with positron emission tomography. These variables were investigated under 90 minutes of pressure exposure caused by two functionally different support surfaces-a regular foam mattress and a minimum pressure air (MPA) mattress.

Results: A total of eight healthy volunteers took part in the study. There was major tissue deformation when the participants lay on a foam mattress while the tissues retained their original shape on the MPA mattress (p<0.0001). During the pressure exposure, the skin temperature increased significantly on both support surfaces but the final temperature on the foam mattress was about 1oC higher than on the MPA mattress (p<0.0001). SEM increased on both support surfaces compared with an unexposed reference site, but the cause may be different between the two support surfaces. Tissue perfusion was lowest in the skin followed by subcutaneous tissues and highest in the muscles. The pressure exposure did not cause any substantial changes in perfusion. The results showed that tissue deformation was more pronounced, the support surface contact area (envelopment), was smaller and the skin temperature higher on the foam mattress than on the MPA mattress, without significant differences in tissue perfusion.

Conclusion: In this study, the MPA mattress support surface had mechanobiological properties that counteracted tissue deformation and thereby may prevent PUs.
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http://dx.doi.org/10.12968/jowc.2021.30.1.54DOI Listing
January 2021

Exercise intensity regulates cytokine and klotho responses in men.

Nutr Diabetes 2021 01 7;11(1). Epub 2021 Jan 7.

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.

Background: Short-term exercise training programs that consist of moderate intensity endurance training or high intensity interval training have become popular choices for healthy lifestyle modifications, with as little as two weeks of training being shown to improve cardiorespiratory fitness and whole-body glucose metabolism. An emerging concept in exercise biology is that exercise stimulates the release of cytokines and other factors into the blood that contribute to the beneficial effects of exercise on metabolism, but whether these factors behave similarly in response to moderate and high intensity short term training is not known. Here, we determined the effects of two short-term exercise training programs on the concentrations of select secreted cytokines and Klotho, a protein involved in anti-aging.

Methods: Healthy, sedentary men (n = 22) were randomized to moderate intensity training (MIT) or sprint intensity training (SIT) treatment groups. SIT consisted of 6 sessions over 2 weeks of 6 × 30 s all out cycle ergometer sprints with 4 min of recovery between sprints. MIT consisted of 6 sessions over 2 weeks of cycle ergometer exercise at 60% VO, gradually increasing in duration from 40 to 60 min. Blood was taken before the intervention and 48 h after the last training session, and glucose uptake was measured using [F]FDG-PET/CT scanning. Cytokines were measured by multiplex and Klotho concentrations by ELISA.

Results: Both training protocols similarly increased VO and decreased fat percentage and visceral fat (P < 0.05). MIT and SIT training programs both reduced the concentrations of IL-6, Hepatocyte Growth Factor (HGF) and Leptin. Interestingly, MIT, but not SIT increased monocyte chemoattractant protein-1 (MCP-1) concentrations, an exercise-induced cytokine, as well as Klotho concentrations.

Conclusion: Short-term exercise training at markedly different intensities similarly improves cardiovascular fitness but results in intensity-specific changes in cytokine responses to exercise.
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http://dx.doi.org/10.1038/s41387-020-00144-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791135PMC
January 2021

Seasonal Variation in the Brain μ-Opioid Receptor Availability.

J Neurosci 2021 Feb 23;41(6):1265-1273. Epub 2020 Dec 23.

Turku PET Centre, University of Turku, FIN-20520 Turku, Finland.

Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported evidence. Here, we first conducted a cross-sectional study with previously acquired human [C]carfentanil PET imaging data (132 male and 72 female healthy subjects) to test whether there is seasonal variation in MOR availability. We then investigated experimentally whether seasonal variation in daylength causally influences brain MOR availability in rats. Rats (six male and three female rats) underwent daylength cycle simulating seasonal changes; control animals (two male and one female rats) were kept under constant daylength. Animals were scanned repeatedly with [C]carfentanil PET imaging. Seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability in humans. Brain regions sensitive to daylength spanned the socioemotional brain circuits, where MOR availability peaked during spring. In rats, MOR availabilities in the brain neocortex, thalamus, and striatum peaked at intermediate daylength. Varying daylength also affected the weight gain and stress hormone levels. We conclude that cerebral MOR availability in humans and rats shows significant seasonal variation, which is predominately associated with seasonal photoperiodic variation. Given the intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior. Seasonal rhythms influence emotion and sociability. The central μ-opioid receptor (MOR) system modulates numerous seasonally varying socioemotional functions, but its seasonal variation remains elusive. Here we used positron emission tomography to show that MOR levels in both human and rat brains show daylength-dependent seasonal variation. The highest MOR availability was observed at intermediate daylengths. Given the intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior.
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http://dx.doi.org/10.1523/JNEUROSCI.2380-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888218PMC
February 2021

Effects of Different Exercise Training Protocols on Gene Expression of Rac1 and PAK1 in Healthy Rat Fast- and Slow-Type Muscles.

Front Physiol 2020 19;11:584661. Epub 2020 Nov 19.

Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland.

Purpose: Rac1 and its downstream target PAK1 are novel regulators of insulin and exercise-induced glucose uptake in skeletal muscle. However, it is not yet understood how different training intensities affect the expression of these proteins. Therefore, we studied the effects of (HIIT) and (MICT) on Rac1 and PAK1 expression in fast-type (, GC) and slow-type (, SOL) muscles in rats after HIIT and MICT swimming exercises.

Methods: The mRNA expression was determined using qPCR and protein expression levels with reverse-phase protein microarray (RPPA).

Results: HIIT significantly mRNA expression in GC compared to MICT ( = 0.003) and to the control group (CON) ( = 0.001). At the protein level Rac1 was in GC in both training groups, but only the difference between HIIT and CON was significant ( = 0.02). HIIT caused significant of mRNA expression in GC compared to MICT ( = 0.007) and to CON ( = 0.001). At the protein level, HIIT increased PAK1 expression in GC compared to MICT and CON (by ∼17%), but the difference was not statistically significant ( = 0.3, = 0.2, respectively). There were no significant differences in the Rac1 or PAK1 expression in SOL between the groups.

Conclusion: Our results indicate that HIIT, but not MICT, Rac1 and PAK1 mRNA expression and the protein expression of especially Rac1 but only in fast-type muscle. These exercise training findings may reveal new therapeutic targets to treat patients with metabolic diseases.
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http://dx.doi.org/10.3389/fphys.2020.584661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711069PMC
November 2020

Both sedentary time and physical activity are associated with cardiometabolic health in overweight adults in a 1 month accelerometer measurement.

Sci Rep 2020 11 25;10(1):20578. Epub 2020 Nov 25.

Turku PET Centre, University of Turku and Turku University Hospital, P.O. box 52, 20521, Turku, Finland.

The aim of this study was to examine the associations of cardiometabolic health markers with device-measured sedentary behavior (SB) duration and different intensities of physical activity (PA) among overweight working-aged adults with low self-reported PA levels. This cross-sectional analysis included 144 subjects (42 men) with mean age of 57 (SD 6.5) years and mean BMI of 31.7 (SD 4) kg/m. SB and standing time, breaks in sedentary time, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured for 4 consecutive weeks (mean 25 days, SD 4) with hip-worn accelerometers. Fasting plasma glucose, insulin, HbA, triglycerides and total cholesterol, HDL and LDL were measured from venous blood samples. HOMA-IR index was calculated as a surrogate of insulin resistance. The associations were examined using linear models. LPA, MVPA, and daily steps associated with better insulin sensitivity and favorable plasma lipid profile, when adjusted for age, sex and BMI, whereas greater proportion of SB associated with insulin resistance and unfavorable lipid profile. As all PA intensities associated with better cardiometabolic health, the total daily duration of PA may be more relevant than intensity in maintaining metabolic health in overweight adults, if the current guidelines for PA are not met.Trial Registration: ClinicalTrials.gov NCT03101228, registered 05/04/2017, https://clinicaltrials.gov/show/NCT03101228 .
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http://dx.doi.org/10.1038/s41598-020-77637-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688927PMC
November 2020

Safety, biodistribution and radiation dosimetry of F-rhPSMA-7.3 in healthy adult volunteers.

J Nucl Med 2020 Oct 16. Epub 2020 Oct 16.

Clinical Research Services Turku - CRST Ltd., Finland.

This first-in-human study investigated the safety, biodistribution and radiation dosimetry of the novel F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) positron emission tomography (PET) imaging agent, F-rhPSMA-7.3. Six healthy volunteer subjects (3 males, 3 females) underwent multiple whole-body PET acquisitions at scheduled time points up to 248 minutes after the administration of F-rhPSMA-7.3 (mean activity 220; range, 210-228 MBq). PET scans were conducted in three separate sessions and subjects were encouraged to void between sessions. Blood and urine samples were collected for up to 4 hours post-injection to assess metabolite-corrected radioactivity in whole blood, plasma and urine. Quantitative measurements of F radioactivity in volumes of interest (VOIs) over target organs were determined directly from the PET images at 8 time points and normalized time-activity concentration curves were generated. These normalized cumulated activities were then inputted into the OLINDA/EXM package to calculate the internal radiation dosimetry and the subjects' effective dose. F-rhPSMA-7.3 was well tolerated. One adverse event (mild headache, not requiring medication) was considered possibly related to F-rhPSMA-7.3: because of the temporal association with F-rhPSMA-7.3 injection, a causal relationship could not be excluded. The calculated effective dose was 0.0141 mSv/MBq when using a 3.5-hour voiding interval. The organs with the highest absorbed dose per unit of administered radioactivity were the adrenals (mean absorbed dose, 0.1835 mSv/MBq), the kidneys (mean absorbed dose, 0.1722 mSv/MBq), the submandibular glands (mean absorbed dose, 0.1479 mSv) and the parotid glands (mean absorbed dose, 0.1137 mSv/MBq). At the end of the first scanning session (mean time, 111 min post-injection), an average of 7.2% (range, 4.4-9.0%) of the injected radioactivity of F-rhPSMA-7.3 was excreted into urine. The safety, biodistribution and internal radiation dosimetry F-rhPSMA-7.3 are considered favorable for PET imaging.
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http://dx.doi.org/10.2967/jnumed.120.252114DOI Listing
October 2020

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery.

Nutr Metab Cardiovasc Dis 2020 11 15;30(12):2363-2371. Epub 2020 Jul 15.

Turku PET Centre, University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland. Electronic address:

Background And Aims: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients.

Methods And Results: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002).

Conclusion: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity.

Clinical Trial Registration Number: NCT01373892.
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http://dx.doi.org/10.1016/j.numecd.2020.07.010DOI Listing
November 2020

Exercise training improves adipose tissue metabolism and vasculature regardless of baseline glucose tolerance and sex.

BMJ Open Diabetes Res Care 2020 08;8(1)

Turku PET Centre, University of Turku, Turku, Finland

Introduction: We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex.

Research Design And Methods: 26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4-6×30 s at maximum effort) and MICT (40-60 min at 60% of maximal aerobic capacity (VO)). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation.

Results: Training increased glucose uptake in VAT (p<0.001) and femoral SAT (p<0.001) and decreased fatty acid uptake in VAT (p=0.01) irrespective of baseline glucose tolerance and sex. In IR participants, training increased adipose tissue vasculature and decreased CD36 and ANGPTL4 gene expression in abdominal SAT. SIT was superior in increasing VO and VAT glucose uptake in the IR group, whereas MICT reduced VAT fatty acid uptake more than SIT.

Conclusions: Short-term training improves adipose tissue metabolism both in healthy and IR participants independently of the sex. Adipose tissue angiogenesis and gene expression was only significantly affected in IR participants.
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http://dx.doi.org/10.1136/bmjdrc-2019-000830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437884PMC
August 2020

Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training.

J Clin Endocrinol Metab 2020 12;105(12)

Turku PET Centre, University of Turku, Turku, Finland.

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 (IR) subjects (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 Ps < 0.0001). FFAU was higher in lumbar and thoracic than femoral BM (both Ps < 0.0001). BM FFAU and femoral BM GU were higher in healthy compared to IR men and in females compared to males (all Ps < 0.05). Training increased femoral BM GU similarly in all groups and decreased lumbar BM FFAU in males (all Ps < 0.05). Osteocalcin and PINP were lower in IR than healthy men and correlated positively with femoral BM GU and glycemic status (all Ps < 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.

Clinical Trial Registration Number: NCT01344928.
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http://dx.doi.org/10.1210/clinem/dgaa516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526736PMC
December 2020

Lowered endogenous mu-opioid receptor availability in subclinical depression and anxiety.

Neuropsychopharmacology 2020 10 30;45(11):1953-1959. Epub 2020 May 30.

Turku PET Centre, University of Turku, Turku, Finland.

Major depressive disorder is associated with lowered mood, anxiety, anhedonia, sleep problems, and cognitive impairments. Many of these functions are regulated by μ-opioid receptor (MOR) system. Preclinical, in vivo, and post-mortem studies have however yielded inconclusive results regarding the role of the MOR in depression and anxiety. Moreover, it is not known whether alterations in MOR are already present in subclinical depression and anxiety. In a large-scale retrospective cross-sectional study we pooled data from 135 (113 males and 22 females) healthy subjects whose brain's MOR availability was measured with positron emission tomography (PET) using an agonist radioligand [C]carfentanil that has high affinity for MORs. Depressive and anxious symptomology was addressed with BDI-II and STAI-X questionnaires, respectively. Both anxiety and depression scores in the subclinical range were negatively associated with MOR availability in cortical and subcortical areas, notably in amygdala, hippocampus, ventral striatum, and orbitofrontal and cingulate cortices. We conclude that dysregulated MOR availability is involved in altered mood and pathophysiology of depression and anxiety disorders.
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http://dx.doi.org/10.1038/s41386-020-0725-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608336PMC
October 2020

Interindividual variability and lateralization of μ-opioid receptors in the human brain.

Neuroimage 2020 08 11;217:116922. Epub 2020 May 11.

Turku PET Centre, University of Turku, Finland; Department of Psychology, University of Turku, Finland.

Alterations in the brain's μ-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. Multiple epidemiological factors have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. We compiled [C]carfentanil positron emission tomography scans from 204 individuals with no neurologic or psychiatric disorders, and estimated the effects of sex, age, body mass index (BMI) and smoking on [C]carfentanil binding potential using between-subject regression analysis. We also examined hemispheric differences in MOR availability. Older age was associated with increase in MOR availability in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders. Lateralized MOR system may reflect hemispheric work specialization in central emotion and pain processes.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116922DOI Listing
August 2020

Changes in quadriceps femoris muscle perfusion following different degrees of cold-water immersion.

J Appl Physiol (1985) 2020 05 30;128(5):1392-1401. Epub 2020 Apr 30.

Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.

We examined the influence of graded cold-water immersion (CWI) on global and regional quadriceps muscle perfusion with positron emission tomography (PET) and [O]HO. In 30 healthy men [33 ± 8 yr; 81 ± 10 kg; 184 ± 5 cm; percentage body fat: 13 ± 5%; peak oxygen uptake (V̇o): 47 ± 8 mL·kg·min] quadriceps perfusion, thigh and calf cutaneous vascular conductance (CVC), intestinal, muscle, and local skin temperatures, thermal comfort, mean arterial pressure, and heart rate were assessed before and after 10 min of CWI at 8°C, 15°C, or 22°C. Global quadriceps perfusion did not change beyond a clinically relevant threshold (0.75 mL·100 g·min) in any condition and was similar between conditions {range of differences [95% confidence interval (CI)]: 0.1 mL·100 g·min (-0.9 to 1.2 mL·100 g·min) to 0.9 mL·100 g·min (-0.2 to 1.9 mL·100 g·min)}. Muscle perfusion was greater in vastus intermedius (VI) compared with vastus lateralis (VL) (2.2 mL·100 g·min; 95% CI 1.5 to 3.0 mL·100 g·min) and rectus femoris (RF) (2.2 mL·100 g·min; 1.4 to 2.9 mL·100 g·min). A clinically relevant increase in VI muscle perfusion after immersion at 8°C and a decrease in RF muscle perfusion at 15°C were observed. A clinically relevant increase in perfusion was observed in VI in 8°C compared with 22°C water (2.3 mL·100 g·min; 1.1 to 3.5 mL·100 g·min). There were no clinically relevant between-condition differences in thigh CVC. Our findings suggest that CWI (8-22°C) does not reduce global quadriceps muscle perfusion to a clinically relevant extent; however, colder water increases (8°C) deep muscle perfusion and reduces (15°C) superficial muscle (RF) perfusion in the quadriceps muscle. Using positron emission tomography, we report for the first time muscle perfusion heterogeneity in the quadriceps femoris in response to different degrees of cold-water immersion (CWI). Noxious CWI temperatures (8°C) increase perfusion in the deep quadriceps muscle, whereas superficial quadriceps muscle perfusion is reduced in cooler (15°C) water. Therefore, these data have important implications for the selection of CWI approaches used in the treatment of soft tissue injury, while also increasing our understanding of the potential mechanisms underpinning CWI.
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http://dx.doi.org/10.1152/japplphysiol.00833.2019DOI Listing
May 2020

Predicting Skeletal Muscle and Whole-Body Insulin Sensitivity Using NMR-Metabolomic Profiling.

J Endocr Soc 2020 Apr 11;4(4):bvaa026. Epub 2020 Mar 11.

Turku PET Centre, University of Turku, Turku, Finland.

Purpose: Abnormal lipoprotein and amino acid profiles are associated with insulin resistance and may help to identify this condition. The aim of this study was to create models estimating skeletal muscle and whole-body insulin sensitivity using fasting metabolite profiles and common clinical and laboratory measures.

Material And Methods: The cross-sectional study population included 259 subjects with normal or impaired fasting glucose or type 2 diabetes in whom skeletal muscle and whole-body insulin sensitivity (M-value) were measured during euglycemic hyperinsulinemic clamp. Muscle glucose uptake (GU) was measured directly using [F]FDG-PET. Serum metabolites were measured using nuclear magnetic resonance (NMR) spectroscopy. We used linear regression to build the models for the muscle GU (Muscle-insulin sensitivity index [ISI]) and M-value (whole-body [WB]-ISI). The models were created and tested using randomly selected training (n = 173) and test groups (n = 86). The models were compared to common fasting indices of insulin sensitivity, homeostatic model assessment-insulin resistance (HOMA-IR) and the revised quantitative insulin sensitivity check index (QUICKI).

Results: WB-ISI had higher correlation with actual M-value than HOMA-IR or revised QUICKI ( = 0.83 vs -0.67 and 0.66;  < 0.05 for both comparisons), whereas the correlation of Muscle-ISI with the actual skeletal muscle GU was not significantly stronger than HOMA-IR's or revised QUICKI's ( = 0.67 vs -0.58 and 0.59; both nonsignificant) in the test dataset.

Conclusion: Muscle-ISI and WB-ISI based on NMR-metabolomics and common laboratory measurements from fasting serum samples and basic anthropometrics are promising rapid and inexpensive tools for determining insulin sensitivity in at-risk individuals.
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http://dx.doi.org/10.1210/jendso/bvaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093091PMC
April 2020

Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia.

Med Sci Sports Exerc 2020 01;52(1):94-104

Turku PET Centre, University of Turku, Turku, FINLAND.

Introduction: Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance.

Methods: Twenty-six, sedentary subjects (prediabetic, n = 9; type 2 diabetes, n = 17; age, 49 [SD, 4] yr; body mass index, 30.5 [SD, 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using positron emission tomography. Gut microbiota composition was analyzed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit.

Results: V˙O2peak improved only after SIT (P = 0.01). Both training modes reduced systematic and intestinal inflammatory markers (tumor necrosis factor-α, lipopolysaccharide binding protein) (time P < 0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time P = 0.03) and decreasing Firmicutes/Bacteroidetes ratio (time P = 0.04). Moreover, there was a decrease in Clostridium genus (time P = 0.04) and Blautia (time P = 0.051). Only MICT decreased jejunal FAU (P = 0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus.

Conclusions: Intestinal substrate uptake associates with gut microbiota composition and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.
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http://dx.doi.org/10.1249/MSS.0000000000002112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028471PMC
January 2020

Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Right and Left Ventricles at Rest and During Exercise Using O-Labeled Compounds and PET.

Front Physiol 2019 19;10:741. Epub 2019 Jun 19.

Turku PET Centre, University of Turku, Turku, Finland.

Simultaneous measurement of right (RV) and left ventricle (LV) myocardial blood flow (MBF), oxygen extraction fraction (OEF), and oxygen consumption (MVO) non-invasively in humans would provide new possibilities to understand cardiac physiology and different patho-physiological states. We developed and tested an optimized novel method to measure MBF, OEF, and MVO simultaneously both in the RV and LV free wall (FW) using positron emission tomography in healthy young men at rest and during supine bicycle exercise. Resting MBF was not significantly different between the three myocardial regions. Exercise increased MBF in the LVFW and septum, but MBF was lower in the RV compared to septum and LVFW during exercise. Resting OEF was similar between the three different myocardial regions (~70%) and increased in response to exercise similarly in all regions. MVO increased approximately two to three times from rest to exercise in all myocardial regions, but was significantly lower in the RV during exercise as compared to septum LVFW. MBF, OEF, and MVO can be assessed simultaneously in the RV and LV myocardia at rest and during exercise. Although there are no major differences in the MBF and OEF between LV and RV myocardial regions in the resting myocardium, MVO per gram of myocardium appears to be lower the RV in the exercising healthy human heart due to lower mean blood flow. The presented method may provide valuable insights for the assessment of MBF, OEF and MVO in hearts in different pathophysiological states.
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http://dx.doi.org/10.3389/fphys.2019.00741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593089PMC
June 2019

TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism.

Nat Metab 2019 02 11;1(2):291-303. Epub 2019 Feb 11.

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.

Exercise improves health and well-being across diverse organ systems, and elucidating mechanisms underlying the beneficial effects of exercise can lead to new therapies. Here, we show that transforming growth factor-β2 (TGF-β2) is secreted from adipose tissue in response to exercise and improves glucose tolerance in mice. We identify TGF-β2 as an exercise-induced adipokine in a gene expression analysis of human subcutaneous adipose tissue biopsies after exercise training. In mice, exercise training increases TGF-β2 in scWAT, serum, and its secretion from fat explants. Transplanting scWAT from exercise-trained wild type mice, but not from adipose tissue-specific Tgfb2-/- mice, into sedentary mice improves glucose tolerance. TGF-β2 treatment reverses the detrimental metabolic effects of high fat feeding in mice. Lactate, a metabolite released from muscle during exercise, stimulates TGF-β2 expression in human adipocytes. Administration of the lactate-lowering agent dichloroacetate during exercise training in mice decreases circulating TGF-β2 levels and reduces exercise-stimulated improvements in glucose tolerance. Thus, exercise training improves systemic metabolism through inter-organ communication with fat via a lactate-TGF-β2-signaling cycle.
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http://dx.doi.org/10.1038/s42255-018-0030-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481955PMC
February 2019

Effects of short-term sprint interval and moderate-intensity continuous training on liver fat content, lipoprotein profile, and substrate uptake: a randomized trial.

J Appl Physiol (1985) 2019 06 18;126(6):1756-1768. Epub 2019 Apr 18.

Turku PET Centre, University of Turku , Turku , Finland.

Type 2 diabetes (T2D) and increased liver fat content (LFC) alter lipoprotein profile and composition and impair liver substrate uptake. Exercise training mitigates T2D and reduces LFC, but the benefits of different training intensities in terms of lipoprotein classes and liver substrate uptake are unclear. The aim of this study was to evaluate the effects of moderate-intensity continuous training (MICT) or sprint interval training (SIT) on LFC, liver substrate uptake, and lipoprotein profile in subjects with normoglycemia or prediabetes/T2D. We randomized 54 subjects (normoglycemic group, = 28; group with prediabetes/T2D, = 26; age = 40-55 yr) to perform either MICT or SIT for 2 wk and measured LFC with magnetic resonance spectroscopy, lipoprotein composition with NMR, and liver glucose uptake (GU) and fatty acid uptake (FAU) using PET. At baseline, the group with prediabetes/T2D had higher LFC, impaired lipoprotein profile, and lower whole body insulin sensitivity and aerobic capacity compared with the normoglycemic group. Both training modes improved aerobic capacity ( < 0.001) and lipoprotein profile (reduced LDL and increased large HDL subclasses; all < 0.05) with no training regimen (SIT vs. MICT) or group effect (normoglycemia vs. prediabetes/T2D). LFC tended to be reduced in the group with prediabetes/T2D compared with the normoglycemic group posttraining ( = 0.051). When subjects were divided according to LFC (high LFC, >5.6%; low LFC, <5.6%), training reduced LFC in subjects with high LFC ( = 0.009), and only MICT increased insulin-stimulated liver GU ( = 0.03). Short-term SIT and MICT are effective in reducing LFC in subjects with fatty liver and in improving lipoprotein profile regardless of baseline glucose tolerance. Short-term MICT is more efficient in improving liver insulin sensitivity compared with SIT. In the short term, both sprint interval training and moderate-intensity continuous training (MICT) reduce liver fat content and improve lipoprotein profile; however, MICT seems to be preferable in improving liver insulin sensitivity.
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http://dx.doi.org/10.1152/japplphysiol.00900.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620664PMC
June 2019

Intramyocellular lipid accumulation after sprint interval and moderate-intensity continuous training in healthy and diabetic subjects.

Physiol Rep 2019 02;7(3):e13980

Turku PET Centre, University of Turku, Turku, Finland.

The effects of sprint interval training (SIT) on intramyocellular (IMCL) and extramyocellular (EMCL) lipid accumulation are unclear. We tested the effects of SIT and moderate-intensity continuous training (MICT) on IMCL and EMCL accumulation in a randomized controlled setting in two different study populations; healthy untrained men (n 28) and subjects with type 2 diabetes (T2D) or prediabetes (n 26). Proton magnetic resonance spectroscopy ( H MRS) was used to determine IMCL and EMCL in the Tibialis anterior muscle (TA) before and after a 2-week exercise period. The exercise period comprised six sessions of SIT or MICT cycling on a cycle ergometer. IMCL increased after SIT compared to MICT (P = 0.042) in both healthy and T2D/prediabetic subjects. On EMCL the training intervention had no significant effect. In conclusion, IMCL serves as an important energy depot during exercise and can be extended by high intensity exercise. The effects of high intensity interval exercise on IMCL seem to be similar regardless of insulin sensitivity or the presence of T2D.
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http://dx.doi.org/10.14814/phy2.13980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369060PMC
February 2019

Muscle Free Fatty-Acid Uptake Associates to Mechanical Efficiency During Exercise in Humans.

Front Physiol 2018 21;9:1171. Epub 2018 Aug 21.

Turku PET Centre, University of Turku, Turku, Finland.

Intrinsic factors related to muscle metabolism may explain the differences in mechanical efficiency (ME) during exercise. Therefore, this study aimed to investigate the relationship between muscle metabolism and ME. Totally 17 healthy recreationally active male participants were recruited and divided into efficient (EF; = 8) and inefficient (IE; = 9) groups, which were matched for age (mean ± SD 24 ± 2 vs. 23 ± 2 years), BMI (23 ± 1 vs. 23 ± 2 kg m), physical activity levels (3.4 ± 1.0 vs. 4.1 ± 1.0 sessions/week), and Opeak (53 ± 3 vs. 52 ± 3 mL kg min), respectively, but differed for ME at 45% of Opeak intensity during submaximal bicycle ergometer test (EF 20.5 ± 3.5 vs. IE 15.4 ± 0.8%, < 0.001). Using positron emission tomography, muscle blood flow (BF) and uptakes of oxygen (m O), fatty acids (FAU) and glucose (GU) were measured during dynamic submaximal knee-extension exercise. Workload-normalized BF (EF 35 ± 14 vs. IE 34 ± 11 mL 100 g min, = 0.896), m O (EF 4.1 ± 1.2 vs. IE 3.9 ± 1.2 mL 100 g min, = 0.808), and GU (EF 3.1 ± 1.8 vs. IE 2.6 ± 2.3 μmol 100 g min, = 0.641) as well as the delivery of oxygen, glucose, and FAU, as well as respiratory quotient were not different between the groups. However, FAU was significantly higher in EF than IE (3.1 ± 1.7 vs. 1.7 ± 0.6 μmol 100 g min, = 0.047) and it also correlated with ME ( = 0.56, = 0.024) in the entire study group. EF group also demonstrated higher use of plasma FAU than IE, but no differences in use of plasma glucose and intramuscular energy sources were observed between the groups. These findings suggest that the effective use of plasma FAU is an important determinant of ME during exercise.
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http://dx.doi.org/10.3389/fphys.2018.01171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110921PMC
August 2018

Increase of Glucose Uptake in Human Bone Marrow With Increasing Exercise Intensity.

Int J Sport Nutr Exerc Metab 2019 May 18;29(3):254-258. Epub 2018 Nov 18.

1 University of Turku.

Human bone marrow is a metabolically active tissue that responds to acute low-intensity exercise by having increased glucose uptake (GU). Here, the authors studied whether bone marrow GU increases more with increased exercise intensities. Femoral bone marrow GU was measured using positron emission tomography and [F]-fluorodeoxyglucose in six healthy young men during cycling at intensities of 30% (low), 55% (moderate), and 75% (high) of maximal oxygen consumption on three separate days. Bone marrow GU at low was 17.2 µmol·kg·min (range 9.0-25.4) and increased significantly ( = .003) at moderate (31.2 µmol·kg·min, 22.9-39.4) but was not significant from moderate to high (37.4 µmol·kg·min, 29.0-45.7,  = .26). Furthermore, the ratio between bone and muscle GU decreased from low to moderate exercise intensity ( < .01) but not ( = .99) from moderate to high exercise intensity. In conclusion, these results show that although the increase is not as large as observed in exercising skeletal muscle, GU in femoral bone marrow increases with increasing exercise intensity at least from low- to moderate-intensity effort, which may be important for bone and whole-body metabolic health.
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http://dx.doi.org/10.1123/ijsnem.2018-0094DOI Listing
May 2019

Aerobic exercise modulates anticipatory reward processing via the μ-opioid receptor system.

Hum Brain Mapp 2018 10 8;39(10):3972-3983. Epub 2018 Jun 8.

Turku PET Centre, University of Turku, Turku, Finland.

Physical exercise modulates food reward and helps control body weight. The endogenous µ-opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise-induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR-selective radioligand [ C]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise-induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise-induced changes in MOR binding correlated negatively with the exercise-induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise-induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control.
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http://dx.doi.org/10.1002/hbm.24224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866313PMC
October 2018

Exercise training decreases pancreatic fat content and improves beta cell function regardless of baseline glucose tolerance: a randomised controlled trial.

Diabetologia 2018 08 2;61(8):1817-1828. Epub 2018 May 2.

Turku PET Centre, University of Turku, P.O. Box 52, FIN-20521, Turku, Finland.

Aims/hypothesis: Pancreatic fat accumulation may contribute to the development of beta cell dysfunction. Exercise training improves whole-body insulin sensitivity, but its effects on pancreatic fat content and beta cell dysfunction are unclear. The aim of this parallel-group randomised controlled trial was to evaluate the effects of exercise training on pancreatic fat and beta cell function in healthy and prediabetic or type 2 diabetic participants and to test whether the responses were similar regardless of baseline glucose tolerance.

Methods: Using newspaper announcements, a total of 97 sedentary 40-55-year-old individuals were assessed for eligibility. Prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes were defined by ADA criteria. Of the screened candidates, 28 healthy men and 26 prediabetic or type 2 diabetic men and women met the inclusion criteria and were randomised into 2-week-long sprint interval or moderate-intensity continuous training programmes in a 1:1 allocation ratio using random permuted blocks. The primary outcome was pancreatic fat, which was measured by magnetic resonance spectroscopy. As secondary outcomes, beta cell function was studied using variables derived from OGTT, and whole-body insulin sensitivity and pancreatic fatty acid and glucose uptake were measured using positron emission tomography. The measurements were carried out at the Turku PET Centre, Finland. The analyses were based on an intention-to-treat principle. Given the nature of the intervention, blinding was not applicable.

Results: At baseline, the group of prediabetic or type 2 diabetic men had a higher pancreatic fat content and impaired beta cell function compared with the healthy men, while glucose and fatty acid uptake into the pancreas was similar. Exercise training decreased pancreatic fat similarly in healthy (from 4.4% [3.0%, 6.1%] to 3.6% [2.4%, 5.2%] [mean, 95% CI]) and prediabetic or type 2 diabetic men (from 8.7% [6.0%, 11.9%] to 6.7% [4.4%, 9.6%]; p = 0.036 for time effect) without any changes in pancreatic substrate uptake (p ≥ 0.31 for time effect in both insulin-stimulated glucose and fasting state fatty acid uptake). In prediabetic or type 2 diabetic men and women, both exercise modes similarly improved variables describing beta cell function.

Conclusions/interpretation: Two weeks of exercise training improves beta cell function in prediabetic or type 2 diabetic individuals and decreases pancreatic fat regardless of baseline glucose tolerance. This study shows that short-term training efficiently reduces ectopic fat within the pancreas, and exercise training may therefore reduce the risk of type 2 diabetes.

Trial Registration: ClinicalTrials.gov NCT01344928 FUNDING: This study was funded by the Emil Aaltonen Foundation, the European Foundation for the Study of Diabetes, the Finnish Diabetes Foundation, the Orion Research Foundation, the Academy of Finland (grants 251399, 256470, 281440, and 283319), the Ministry of Education of the State of Finland, the Paavo Nurmi Foundation, the Novo Nordisk Foundation, the Finnish Cultural Foundation, the Hospital District of Southwest Finland, the Turku University Foundation, and the Finnish Medical Foundation.
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http://dx.doi.org/10.1007/s00125-018-4627-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061150PMC
August 2018

μ-opioid receptor system mediates reward processing in humans.

Nat Commun 2018 04 16;9(1):1500. Epub 2018 Apr 16.

Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland.

The endogenous μ-opioid receptor (MOR) system regulates motivational and hedonic processing. We tested directly whether individual differences in MOR are associated with neural reward responses to food pictures in humans. We scanned 33 non-obese individuals with positron emission tomography (PET) using the MOR-specific radioligand [C]carfentanil. During a functional magnetic resonance imaging (fMRI) scan, the subjects viewed pictures of appetizing versus bland foods to elicit reward responses. MOR availability was measured in key components of the reward and emotion circuits and used to predict BOLD-fMRI responses to foods. Viewing palatable versus bland foods activates regions involved in homeostatic and reward processing, such as amygdala, ventral striatum, and hypothalamus. MOR availability in the reward and emotion circuit is negatively associated with the fMRI reward responses. Variation in MOR availability may explain why some people feel an urge to eat when encountering food cues, increasing risk for weight gain and obesity.
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http://dx.doi.org/10.1038/s41467-018-03848-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902580PMC
April 2018

Insulin-stimulated glucose uptake in skeletal muscle, adipose tissue and liver: a positron emission tomography study.

Eur J Endocrinol 2018 May 13;178(5):523-531. Epub 2018 Mar 13.

Turku PET Centre, University of TurkuTurku, Finland

Objective: Insulin resistance is reflected by the rates of reduced glucose uptake (GU) into the key insulin-sensitive tissues, skeletal muscle, liver and adipose tissue. It is unclear whether insulin resistance occurs simultaneously in all these tissues or whether insulin resistance is tissue specific.

Design And Methods: We measured GU in skeletal muscle, adipose tissue and liver and endogenous glucose production (EGP), in a single session using F-fluorodeoxyglucose with positron emission tomography (PET) and euglycemic-hyperinsulinemic clamp. The study population consisted of 326 subjects without diabetes from the CMgene study cohort.

Results: Skeletal muscle GU less than 33 µmol/kg tissue/min and subcutaneous adipose tissue GU less than 11.5 µmol/kg tissue/min characterized insulin-resistant individuals. Men had considerably worse insulin suppression of EGP compared to women. By using principal component analysis (PCA), BMI inversely and skeletal muscle, adipose tissue and liver GU positively loaded on same principal component explaining one-third of the variation in these measures. The results were largely similar when liver GU was replaced by EGP in PCA. Liver GU and EGP were positively associated with aging.

Conclusions: We have provided threshold values, which can be used to identify tissue-specific insulin resistance. In addition, we found that insulin resistance measured by GU was only partially similar across all insulin-sensitive tissues studied, skeletal muscle, adipose tissue and liver and was affected by obesity, aging and gender.
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http://dx.doi.org/10.1530/EJE-17-0882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920018PMC
May 2018

Brown adipose tissue lipid metabolism in morbid obesity: Effect of bariatric surgery-induced weight loss.

Diabetes Obes Metab 2018 05 22;20(5):1280-1288. Epub 2018 Feb 22.

Turku PET Centre, University of Turku, Turku, Finland.

Objective: We aimed to investigate the effect of bariatric surgery on lipid metabolism in supraclavicular brown adipose tissue in morbidly obese women. We hypothesized that lipid metabolism improves after surgery-induced weight loss.

Materials And Methods: A total of 23 morbidly obese women (BMI, 42.1 ± 4.2 kg/m ; age, 43.8 ± 9.8 years) were assessed before and 6 months after bariatric surgery and 15 age- and sex-matched controls (22.6 ± 2.8 kg/m ) were assessed once. In the supraclavicular fat depot, fractional (FUR) and NEFA uptake rates were measured with F-FTHA-PET. We assessed tissue morphology (triglyceride content) using computed tomography (CT)-radiodensity (in Hounsfield Units[HU]) and the proportion of fat with high density (sBAT [%]) in the entire supraclavicular fat depot.

Results: The supraclavicular fractional uptake rate was lower in obese women compared to controls (0.0055 ± 0.0035 vs 0.0161 ± 0.0177 1/min, P = .001). Both FUR (to 0.0074 ± 0.0035 1/min, P = .01) and NEFA uptake rates (to 0.50 ± 0.50 μmol/100 g/min, P = .001) increased after surgery. Compared to controls, obese women had lower CT-radiodensity (-101.2 ± 10.1 vs -82.5 ± 5.8 HU, P < .001) and sBAT (43.4 ± 8.4% vs 64.5 ± 12.4%, P < .001). After surgery, CT-radiodensity increased (to -82.5 ± 9.6 HU, P < .001), signifying decreased triglyceride content and sBAT improved (to 58.0 ± 10.7%, P < .001), indicating an increased proportion of brown fat. The change in tissue morphology, reflected as increase in CT-radiodensity and sBAT (%), was associated with a decrease in adiposity indices and an increase in whole-body insulin sensitivity.

Conclusions: A decrease in triglyceride content, coupled with the increased proportion of brown adipose tissue in the supraclavicular fat depot, may play a role in the improvement of whole-body insulin sensitivity observed in morbidly obese women after surgery-induced weight loss.
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http://dx.doi.org/10.1111/dom.13233DOI Listing
May 2018

Short-term interval training alters brain glucose metabolism in subjects with insulin resistance.

J Cereb Blood Flow Metab 2018 10 29;38(10):1828-1838. Epub 2017 Sep 29.

1 Turku PET Centre, University of Turku, Turku, Finland.

Brain insulin-stimulated glucose uptake (GU) is increased in obese and insulin resistant subjects but normalizes after weight loss along with improved whole-body insulin sensitivity. Our aim was to study whether short-term exercise training (moderate intensity continuous training (MICT) or sprint interval training (SIT)) alters substrates for brain energy metabolism in insulin resistance. Sedentary subjects ( n = 21, BMI 23.7-34.3 kg/m, age 43-55 y) with insulin resistance were randomized into MICT ( n = 11, intensity≥60% of VO) or SIT ( n = 10, all-out) groups for a two-week training intervention. Brain GU during insulin stimulation and fasting brain free fatty acid uptake (FAU) was measured using PET. At baseline, brain GU was positively associated with the fasting insulin level and negatively with the whole-body insulin sensitivity. The whole-body insulin sensitivity improved with both training modes (20%, p = 0.007), while only SIT led to an increase in aerobic capacity (5%, p = 0.03). SIT also reduced insulin-stimulated brain GU both in global cortical grey matter uptake (12%, p = 0.03) and in specific regions ( p < 0.05, all areas except the occipital cortex), whereas no changes were observed after MICT. Brain FAU remained unchanged after the training in both groups. These findings show that short-term SIT effectively decreases insulin-stimulated brain GU in sedentary subjects with insulin resistance.
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http://dx.doi.org/10.1177/0271678X17734998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168908PMC
October 2018

Sprint interval training decreases left-ventricular glucose uptake compared to moderate-intensity continuous training in subjects with type 2 diabetes or prediabetes.

Sci Rep 2017 09 5;7(1):10531. Epub 2017 Sep 5.

Turku PET Centre, University of Turku, Turku, Finland.

Type 2 diabetes mellitus (T2DM) is associated with reduced myocardial glucose uptake (GU) and increased free fatty acid uptake (FFAU). Sprint interval training (SIT) improves physical exercise capacity and metabolic biomarkers, but effects of SIT on cardiac function and energy substrate metabolism in diabetic subjects are unknown. We tested the hypothesis that SIT is more effective than moderate-intensity continuous training (MICT) on adaptations in left and right ventricle (LV and RV) glucose and fatty acid metabolism in diabetic subjects. Twenty-six untrained men and women with T2DM or prediabetes were randomized into two-week-long SIT (n = 13) and MICT (n = 13) interventions. Insulin-stimulated myocardial GU and fasted state FFAU were measured by positron emission tomography and changes in LV and RV structure and function by cardiac magnetic resonance. In contrast to our hypothesis, SIT significantly decreased GU compared to MICT in LV. FFAU of both ventricles remained unchanged by training. RV end-diastolic volume (EDV) and RV mass increased only after MICT, whereas LV EDV, LV mass, and RV and LV end-systolic volumes increased similarly after both training modes. As SIT decreases myocardial insulin-stimulated GU compared to MICT which may already be reduced in T2DM, SIT may be metabolically less beneficial than MICT for a diabetic heart.
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http://dx.doi.org/10.1038/s41598-017-10931-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585392PMC
September 2017

Affective Adaptation to Repeated SIT and MICT Protocols in Insulin-Resistant Subjects.

Med Sci Sports Exerc 2018 Jan;50(1):18-27

1Turku PET Centre, University of Turku, Turku, FINLAND; 2Department of Psychology, University of Turku, Turku, FINLAND; 3Department of Nursing Science, University of Turku, Turku, FINLAND; and 4Department of Biostatistics, University of Turku, Turku, FINLAND.

Introduction: The aim of this study was to investigate affective responses to repeated sessions of sprint interval training (SIT) in comparison with moderate-intensity continuous training (MICT) in insulin-resistant subjects.

Methods: Twenty-six insulin-resistant adults (age, 49 (4) yr; 10 women) were randomized into SIT (n = 13) or MICT (n = 13) groups. Subjects completed six supervised training sessions within 2 wk (SIT session, 4-6 × 30 s all-out cycling/4-min recovery; MICT session, 40-60 min at 60% peak work load). Perceived exertion, stress, and affective state were assessed with questionnaires before, during and after each training session.

Results: Perceived exertion, displeasure, and arousal were higher during the SIT compared with MICT sessions (all P < 0.01). These, however, alleviated similarly in response to SIT and MICT over the 6 d of training (all P < 0.05). SIT versus MICT exercise increased perceived stress and decreased positive affect and feeling of satisfaction acutely after exercise especially in the beginning of the intervention (all P < 0.05). These negative responses declined significantly during the training period: perceived stress and positive activation were no longer different between the training groups after the third, and satisfaction after the fifth training session (P > 0.05).

Conclusions: The perceptual and affective responses are more negative both during and acutely after SIT compared with MICT in untrained insulin-resistant adults. These responses, however, show significant improvements already within six training sessions, indicating rapid positive affective and physiological adaptations to continual exercise training, both SIT and MICT. These findings suggest that even very intense SIT is mentally tolerable alternative for untrained people with insulin resistance.
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http://dx.doi.org/10.1249/MSS.0000000000001415DOI Listing
January 2018

Opioid Release after High-Intensity Interval Training in Healthy Human Subjects.

Neuropsychopharmacology 2018 Jan 19;43(2):246-254. Epub 2017 Jul 19.

Turku PET Centre, University of Turku, Turku, Finland.

Central opioidergic mechanisms may modulate the positive effects of physical exercise such as mood elevation and stress reduction. How exercise intensity and concomitant effective changes affect central opioidergic responses is unknown. We studied the effects of acute physical exercise on the cerebral μ-opioid receptors (MOR) of 22 healthy recreationally active males using positron emission tomography (PET) and the MOR-selective radioligand [C]carfentanil. MOR binding was measured in three conditions on separate days: after a 60-min aerobic moderate-intensity exercise session, after a high-intensity interval training (HIIT) session, and after rest. Mood was measured repeatedly throughout the experiment. HIIT significantly decreased MOR binding selectively in the frontolimbic regions involved in pain, reward, and emotional processing (thalamus, insula, orbitofrontal cortex, hippocampus, and anterior cingulate cortex). Decreased binding correlated with increased negative emotionality. Moderate-intensity exercise did not change MOR binding, although increased euphoria correlated with decreased receptor binding. These observations, consistent with endogenous opioid release, highlight the role of the μ-opioid system in mediating affective responses to high-intensity training as opposed to recreational moderate physical exercise.
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http://dx.doi.org/10.1038/npp.2017.148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729560PMC
January 2018