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Our aim was to compare three research-grade accelerometers for their accuracy in step detection and energy expenditure (EE) estimation in a laboratory setting, at different speeds, especially in overweight/obese participants. Forty-eight overweight/obese subjects participated. Participants performed an exercise routine on a treadmill with six different speeds (1.5, 3, 4.5, 6, 7.5, and 9 km/h) for 4 min each. The exercise was recorded on video and subjects wore three accelerometers during the exercise: Sartorio Xelometer (SX, hip), activPAL (AP, thigh), and ActiGraph GT3X (AG, hip), and energy expenditure (EE) was estimated using indirect calorimetry for comparisons. For step detection, speed-wise mean absolute percentage errors for the SX ranged between 9.73–2.26, 6.39–0.95 for the AP, and 88.69–2.63 for the AG. The activPALs step detection was the most accurate. For EE estimation, the ranges were 21.41–15.15 for the SX, 57.38–12.36 for the AP, and 59.45–28.92 for the AG. All EE estimation errors were due to underestimation. All three devices were accurate in detecting steps when speed exceeded 4 km/h and inaccurate in EE estimation regardless of speed. Our results will guide users to recognize the differences, weaknesses, and strengths of the accelerometer devices and their algorithms.

Summary Multiple endocrine neoplasia type 1 NM_001370259.2(MEN1):c.466G>C(p.Gly156Arg) is characterized by tumors of various endocrine organs. We report on a rare, growth hormone-releasing hormone (GHRH)-releasing pancreatic tumor in a MEN1 patient with a long-term follow-up after surgery. A 22-year-old male with MEN1 syndrome, primary hyperparathyroidism and an acromegalic habitus was observed to have a pancreatic tumor on abdominal CT scanning, growth hormone (GH) and insulin-like growth factor 1 (IGF1) were elevated and plasma GHRH was exceptionally high. GHRH and GH were measured before the treatment and were followed during the study. During octreotide treatment, IGF1 normalized and the GH curve was near normal. After surgical treatment of primary hyperparathyroidism, a pancreatic tail tumor was enucleated. The tumor cells were positive for GHRH antibody staining. After the operation, acromegaly was cured as judged by laboratory tests. No reactivation of acromegaly has been seen during a 20-year follow-up. In conclusion, an ectopic GHRH-producing, pancreatic endocrine neoplasia may represent a rare manifestation of MEN1 syndrome.

Milk is an evolutionary benefit for humans. For infants, it offers optimal nutrients for normal growth, neural development, and protection from harmful microbes. Humans are the only mammals who drink milk throughout their life. Lipids in colostrum originate mostly from milk fat globule membrane (MFGM) droplets extruded from the mammary gland. The MFGM gained much interest as a potential nutraceutical, due to their high phospholipid (PL), ganglioside (GD), and protein contents. In this review, we focused on health effects of MFGM ingredients and dairy food across the life span, especially on neurodevelopment, cardiometabolic health, and frailty in older adults. The MFGM supplements to infants and children reduced gastrointestinal and respiratory tract infections and improved neurodevelopment due to the higher content of protein, PL, and GD in MFGM. The MFGM formulas containing PL and GD improved brain myelination and fastened nerve conduction speed, resulting in improved behavioral developments. Administration of MFGM-rich ingredients improved insulin sensitivity and decreased inflammatory markers, LDL-cholesterol, and triglycerides by lowering intestinal absorption of cholesterol and increasing its fecal excretion. The MFGM supplements, together with exercise, improved ambulatory activities, leg muscle mass, and muscle fiber velocity in older adults. There are great variations in the composition of lipids and proteins in MFGM products, which make comparisons of the different studies impossible. In addition, investigations of the individual MFGM components are required to evaluate their specific effects and molecular mechanisms. Although we are currently only beginning to understand the possible health effects of MFGM products, the current MFGM supplementation trials as presented in this review have shown significant clinical health benefits across the human life span, which are worth further investigation.

Physical activity (PA) is one of the most efficient ways to prevent obesity and its associated diseases worldwide. In the USA, less than 10% of the adult population were able to meet the PA recommendations when accelerometers were used to assess PA habituation. Accelerometers significantly differ from each other in step recognition and do not reveal raw data. The aim of our study was to compare a novel accelerometer, Sartorio Xelometer, which enables to gather raw data, with existing accelerometers ActiGraph GT3X+ and activPAL in terms of step detection and energy expenditure estimation accuracy. 53 healthy subjects were divided into 2 cohorts (cohort 1 optimization; cohort 2 validation) and wore 3 accelerometers and performed an exercise routine consisting of the following speeds: 1.5, 3, 4.5, 9 and 10.5 km/h (6 km/h for 2nd cohort included). Data from optimization cohort was used to optimize Sartorio step detection algorithm. Actual taken steps were recorded with a video camera and energy expenditure (EE) was measured. To observe the similarity between video and accelerometer step counts, paired samples t test and intraclass correlation were used separately for step counts in different speeds and for total counts as well as EE estimations. In speeds of 1.5, 3, 4.5, 6, 9 and 10.5 km/h mean absolute percentage error (MAPE) % were 8.1, 3.5, 4.3, 4.2, 3.1 and 7.8 for the Xelometer, respectively (after optimization). For ActiGraph GT3X+ the MAPE-% were 96.93 (87.4), 34.69 (23.1), 2.13 (2.3), 1.96 (2.6) and 2.99 (3.8), respectively and for activPAL 6.55 (5.6), 1.59 (0.6), 0.81 (1.1), 10.60 (10.3) and 15.76 (13.8), respectively. Significant intraclass correlations were observed with Xelometer estimates and actual steps in all speeds. Xelometer estimated the EE with a MAPE-% of 30.3, activPAL and ActiGraph GT3X+ with MAPE percentages of 20.5 and 24.3, respectively. The Xelometer is a valid device for assessing step counts at different gait speeds. MAPE is differe

Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades low-density lipoprotein cholesterol (LDL-C) receptors, and thus regulates the LDL-C levels in the circulation. Type 2 diabetics often have elevated LDL-C levels. However, the functions of PCSK9 in patients with alterations of glu-cose metabolism and statin therapy are still unclear. Method: we investigated a large cohort of 608 subjects, born in 1945 in Oulu, Finland (Oulu Cohort 1945). We studied the effects of PSCK9 lev-els with different glucose tolerances (normal glucose tolerance (NGT), prediabetes (PreDM) or type 2 diabetes (T2D)) with and without statin medication, and analyzed clinical data, NMR metabolomics and PCSK9 plasma levels. Results: PCSK9 plasma levels did not significantly differ between the three groups. Statin therapy significantly increased the PCSK9 levels in NGT, PreDM and T2D groups compared with subjects with no statins. In the NGT group, negative associations between PCSK9 and LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol and LDL and IDL triglycerides were observed under statin medication. In contrast, in the PreDM and T2D groups, these associa-tions were lost. Conclusions: our data suggest that in subjects with abnormal glucose metabolism and statin therapy, the significant PCSK9-mediated effects on the lipid metabolites are lost com-pared to NGT subjects, but statins reduced the LDL-C and VLDL-C levels.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a liver serine protease regulating LDL cholesterol metabolism. PCSK9 binds to LDL receptors and guides them to lysosomes for degradation, thus increasing the amount of circulating LDL cholesterol. The aim of the study was to investigate associations between physical activity and plasma PCSK9 in subjects with high risk for type 2 diabetes (T2D). Methods: Sixty-eight subjects from both genders with a high risk for T2D were included to a randomized controlled trial with a 3-month physical activity intervention. Physical activity intensities and frequencies were monitored throughout the intervention using a hip worn portable accelerometer. The plasma was collected before and after intervention for analysis of PCSK9 and cardiovascular biomarkers. Results: Plasma PCSK9 did not relate to physical activity although number of steps were 46% higher in the intervention group than in the control group (p < 0.029). Total cholesterol was positively correlated with plasma PCSK9 (R = 0.320, p = 0.008), while maximal oxygen uptake was negatively associated (R = −0.252, p = 0.044). After the physical activity intervention PCSK9 levels were even stronger inversely associated with maximal oxygen uptake (R = −0.410, p = 0.0008) and positively correlated with HDL cholesterol (R = 0.264, p = 0.030). Interestingly, plasma PCSK9 levels were higher in the beginning than at the end of the study. Conclusion: The low physical activity that our subjects with high risk for T2D could perform did not influence plasma PCSK9 levels. Intervention with higher physical activities might be more effective in influencing PCSK9 levels.

Orexin-A (OXA) has been originally isolated from a precursor peptide prepro-orexin from the lateral hypothalamus. The orexin system has been attributed to important functions in sleep, arousal and regulation of energy homeostasis. In addition to its high levels in cerebrospinal fluid, OXA is present in blood. However, reported peptide concentrations in plasma vary significantly depending on the method used. Therefore, a specific and sensitive OXA radioimmunoassay (RIA) with solid phase extraction method was developed to determine whether plasma OXA concentrations is affected by acute feeding and/or wake and sleep in young healthy males. Blood samples were collected for 24 h from nine healthy males (aged 20–24 years; BMI 20.7–26.5) every 2 h starting at 11 a.m. Food was served at 12 p.m, 5:30 p.m, 8 p.m and 8 a.m and the sleep time was between 10 p.m and 7 a.m. Plasma samples were analyzed in addition for cortisol and melatonin levels. Blood pressure was monitored through the experimental period. OXA antibody was raised in rabbits. OXA antiserum had only minor cross-reactivity with prepro-orexin precursor (<0.001%), amino-terminal peptide (<0.001%), carboxy-terminal peptide (0.001%), and orexin-B (0.3%) with high sensitivity (0.15 pg/tube). Plasma OXA levels varied between 0.5 and 16 pg/ml in seven subjects and were undetectable (below 0.5 pg/ml) in two subjects. The OXA concentrations did not correlate to feeding nor wake/sleep, whereas cortisol, melatonin and mean arterial blood pressure presented a clear circadian rhythm in each subject. In conclusion, OXA is present in blood in low amounts and its levels do not follow autonomic nor neuroendocrine circadian rhythms. Thereby, studies examining regulatory mechanisms and influences of OXA from blood samples should interpret results very cautiously.

Our objectives were to determine if there are quantitative associations between amounts and intensities of physical activities (PA) on NMR biomarkers and changes in skeletal muscle gene expressions in subjects with high risk for type 2 diabetes (T2D) performing a 3-month PA intervention. We found that PA was associated with beneficial biomarker changes in a factor containing several VLDL and HDL subclasses and lipids in principal component analysis (P = <0.01). Division of PA into quartiles demonstrated significant changes in NMR biomarkers in the 2nd – 4th quartiles compared to the 1st quartile representing PA of less than 2850 daily steps (P = 0.0036). Mediation analysis of PA-related reductions in lipoproteins showed that the effects of PA was 4–15 times greater than those of body weight or fat mass reductions. In a subset study in highly active subjects’ gene expressions of oxidative fiber markers, Apo D, and G0/G1 Switch Gene 2, controlling insulin signaling and glucose metabolism were significantly increased. Slow walking at speeds of 2–3 km/h exceeding 2895 steps/day attenuated several circulating lipoprotein lipids. The effects were mediated rather by PA than body weight or fat loss. Thus, lower thresholds for PA may exist for long term prevention of cardio-metabolic diseases in sedentary overweight subjects.

Mice are used extensively in physiological research. Automated home‐cage systems have been developed to study single‐housed animals. Increased stress by different housing conditions might affect greatly the results when investigating metabolic responses. Urinary corticosteroid concentration is considered as a stress marker. The aim of the study was to compare the effects of different housing conditions and an automated home‐cage system with indirect calorimetry located in an environmental chamber on corticosterone levels in mice. Male mice were housed in different conditions and in automated home‐cage system to evaluate the effects of housing and measuring conditions on urine corticosterone levels. Corticosterone levels in single‐housed mice in the laboratory animal center were consistently lower compared with the group‐housed mice. Single‐housed mice in a separate, small animal unit showed a rise in their corticosterone levels a day after they were separated to their individual cages, which decreased during the following 2 days. The corticosterone levels of group‐housed mice in the same unit were increased during the first 7 days and then decreased. On day 7, the corticosterone concentrations of group‐housed mice were significantly higher compared with that of single‐housed mice, including the metabolic measurement protocol. In conclusion, single housing caused less stress when compared with group‐housed mice. In addition, the urine corticosterone levels were decreased in single‐housed mice before the metabolic measurement started. Thus, stress does not affect the results when utilizing the automated system for measuring metabolic parameters like food and water intake and calorimetry.

Orexins, or hypocretins, are peptides originally found in the hypothalamus, and have been shown to be involved in the stabilization and maintenance of sleep and wakefulness. In addition, these peptides are known for their actions on energy homeostasis by increased heat production or physical activity. Previous results suggest them to be also involved in peripheral actions on the regulation of intestinal secretion, depending on the subject’s nutritional status (fasted-fed). Orexin-A and Orexin-B peptides, are derived from the prepro-orexin precursor protein. These ligands bind to two G-protein-coupled receptors, orexin-1 and -2 -receptors. Despite intensive research, the role of orexins has not yet been clarified. The aim of the present study was to investigate the role of orexins and their receptors on sleep and wake patterns, energy homeostasis and intestinal secretion. The effects of orexins on sleep and wakefulness, and energy homeostasis were studied in a novel transgenic mouse line, overexpressing the human prepro-orexin gene. The overexpression of prepro-orexin and orexin-A was confirmed in the hypothalami of transgenic mice. The transgenic mice showed a significant reduction in their REM sleep during day and night time, and differences in their vigilance states in the light/dark transition periods. In addition, the mice demonstrated a significantly elevated day time food intake at room temperature, and an increased metabolic heat production independent of uncoupling protein 1 mediated thermogenesis in brown adipose tissue. Instead, transgenic mice showed increased levels of uncoupling protein 2 in white adipose tissue. Furthermore, transgenic mice significantly decreased their total locomotor activity during the first two nights in response to cold exposure (+4°C). The effect of orexins and their receptors on duodenal HCO3– secretion were studied after an overnight (16 h) food deprivation in an in situ perfused organ. Fasting decreased the expression