Identification of doping suspicions through artificial intelligence-powered analysis on athlete's performance passport in female weightlifting.

Introduction: Doping remains a persistent concern in sports, compromising fair competition. The Athlete Biological Passport (ABP) has been a standard anti-doping measure, but confounding factors challenge its effectiveness. Our study introduces an artificial intelligence-driven approach for identifying potential doping suspicious, utilizing the Athlete's Performance Passport (APP), which integrates both demographic profiles and performance data, among elite female weightlifters. Methods: Analyzing publicly available performance data in female weightlifting from 1998 to 2020, along with demographic information, encompassing 17,058 entities, we categorized weightlifters by age, body weight (BW) class, and performance levels. Documented anti-doping rule violations (ADRVs) cases were also retained. We employed AI-powered algorithms, including XGBoost, Multilayer Perceptron (MLP), and an Ensemble model, which integrates XGBoost and MLP, to identify doping suspicions based on the dataset we obtained. Results: Our findings suggest a potential doping inclination in female weightlifters in their mid-twenties, and the sanctioned prevalence was the highest in the top 1% performance level and then decreased thereafter. Performance profiles and sanction trends across age groups and BW classes reveal consistently superior performances in sanctioned cases. The Ensemble model showcased impressive predictive performance, achieving a 53.8% prediction rate among the weightlifters sanctioned in the 2008, 2012, and 2016 Olympics. This demonstrated the practical application of the Athlete's Performance Passport (APP) in identifying potential doping suspicions. Discussion: Our study pioneers an AI-driven APP approach in anti-doping, offering a proactive and efficient methodology. The APP, coupled with advanced AI algorithms, holds promise in revolutionizing the efficiency and objectivity of doping tests, providing a novel avenue for enhancing anti-doping measures in elite female weightlifting and potentially extending to diverse sports. We also address the limitation of a constrained set of APPs, advocating for the development of a more accessible and enriched APP system for robust anti-doping practices.

A rationally designed miniature of soluble methane monooxygenase enables rapid and high-yield methanol production in Escherichia coli.

Soluble methane monooxygenase (sMMO) oxidizes a wide range of carbon feedstocks (C1 to C8) directly using intracellular NADH and is a useful means in developing green routes for industrial manufacturing of chemicals. However, the high-throughput biosynthesis of active recombinant sMMO and the ensuing catalytic oxidation have so far been unsuccessful due to the structural and functional complexity of sMMO, comprised of three functionally complementary components, which remains a major challenge for its industrial applications. Here we develop a catalytically active miniature of sMMO (mini-sMMO), with a turnover frequency of 0.32 s-1, through an optimal reassembly of minimal and modified components of sMMO on catalytically inert and stable apoferritin scaffold. We characterise the molecular characteristics in detail through in silico and experimental analyses and verifications. Notably, in-situ methanol production in a high-cell-density culture of mini-sMMO-expressing recombinant Escherichia coli resulted in higher yield and productivity (~ 3.0 g/L and 0.11 g/L/h, respectively) compared to traditional methanotrophic production.

Follistatin-like 1 is a myokine regulating lipid mobilization during endurance exercise and recovery.

OBJECTIVE: The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. METHODS: Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined. RESULTS: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. CONCLUSIONS: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes.

Theoretical and Experimental Analysis of Osmotically Assisted Reverse Osmosis for Minimum Liquid Discharge.

Osmotically assisted reverse osmosis (OARO) is an innovative process that shows promising potential in the treatment of brine produced by conventional reverse osmosis (RO) systems. This study presents a theoretical and experimental analysis of the OARO process, focusing on its application to achieve minimum liquid discharge (MLD). This theoretical analysis includes the development of a mathematical model to describe the transport phenomena occurring during OARO. By considering mass balance equations coupled with transport equations, the theoretical model allows for the simulation of a full-scale system consisting of a single-stage RO and a four-stage OARO. Experimental investigations are also conducted to validate the theoretical model and to evaluate the performance of the OARO process. A laboratory-scale OARO system is designed and operated using a synthetic RO brine. Various operating conditions, including applied pressure, feed concentration, and draw concentration, are varied to investigate their effects on process performance. The experimental results demonstrate the feasibility of OARO as an MLD solution and also validate the predictions of the theoretical model, confirming its reliability for process optimization and design. The results of the theoretical analysis show that OARO has the potential to significantly improve water recovery compared to conventional RO. Based on the simulation, the optimal operating conditions are explored, leading to a significant reduction (up to 89%) in the volume of brine discharge.

Exploring the Relationships Among (COVID)-19 Stress, Leisure Constraints, and Happiness for Adults During the (COVID)-19 Pandemic in Korea.

Objectives: The emergence of COVID-19 and its consequences has led to fears, worries, discomfort, depression, and anxiety for human beings worldwide. In this study, we examined the relationships among COVID-19 stress, leisure constraints, and happiness of Korean adults. Methods: We employed on-line convenience sampling to recruit participants. The sample consisted of Korean adults. A total of 600 surveys were distributed, we retained 293 responses for analysis. Results: COVID-19 stress subcomponents significantly impacted on individual happiness. Our findings align with research focusing on positive correlates between perceived COVID-19 stress and leisure constraints subcomponents. We also found that as COVID-19 stress decreased, perceived happiness increased. Conclusions: Future research is proposed to explore the mechanism of how leisure constraints influence the engagement of physical activities and strategies of leisure constraints negotiation to gain the benefits of happiness in the pandemic crisis. Managerial implications and future research are discussed from the perspectives of constraint negotiation and happiness.

Identifying the Relationship between Leisure Walking and Prevalence of Alzheimer's Disease and Other Dementias.

The literature suggests that leisure walking can play an important role in preventing dementia. The purpose of the present study was to investigate the relationship between leisure walking and the prevalence of Alzheimer's disease (AD) and other dementias among older adults. Using the 2020 Health and Retirement Study (HRS), 4581 responses constituted the sample for the present study. A hierarchical logit regression analysis was conducted to investigate the relationship between leisure walking and the prevalence of AD and dementia. The results show that leisure walking has been negatively associated with the prevalence of AD and other dementias-that is, they indicate that older adults who frequently engaged in leisure walking were less likely to develop AD and other dementias. This finding suggests the importance of leisure walking as a dementia prevention program for older adults.

The Effects of C. lacerata on Insulin Resistance in Type 2 Diabetes Patients.

BACKGROUND: Several experimental studies have suggested beneficial effects of Ceriporia lacerata on glucose metabolism. However, there has been no human study assessing the effects of C. lacerata on glucose metabolism. Therefore, we investigated whether C. lacerata improves glucose control and insulin resistance in type 2 diabetes patients. METHODS: Ninety patients diagnosed with type 2 diabetes (T2DM) for more than 6 months were enrolled. Subjects were randomly divided into placebo (n = 45) or C. lacerata (n = 45) groups and then assigned to take placebo or C. lacerata capsules (500 mg/capsule) for a 12-week intervention period. Biochemical markers, including fasting glucose, 2-hour postprandial plasma glucose, and lipid profile levels, as well as insulin, c-peptide, and Hba1c, were measured. Furthermore, insulin sensitivity indices, such as HOMA-IR, HOMA-beta, and QUICKI, were assessed before and after the 12-week administration. RESULTS: Eighty-four patients completed the study. There were no significant differences in fasting, postprandial glucose, HbA1c, or lipid parameters. HOMA-IR and QUICKI indices were improved at week 12 in the C. lacerata group, especially in subjects with HOMA-IR of 1.8 or more (p < 0.05). Fasting, postprandial c-peptide, and insulin levels decreased at week 12 in the C. lacerata group (p < 0.05). These significant differences were not observed in the placebo group. CONCLUSION: Twelve-week administration of C. lacerata in T2DM patients resulted in significant improvement in insulin resistance, especially in those with lower insulin sensitivity. A larger population study with a longer follow-up period and an effort to elucidate the mechanism is warranted to further assess the effects of C. lacerata on T2DM patients.

Antioxidant-Rich Dietary Intervention Improves Cardiometabolic Profiles and Arterial Stiffness in Elderly Koreans with Metabolic Syndrome.

PURPOSE: Oxidative stress plays an important role in the pathogenesis of chronic metabolic diseases. This study investigated the effect of the antioxidant-rich dietary intervention on oxidative stress, metabolic parameters, and arterial stiffness in elderly Koreans with metabolic syndrome (MetS). MATERIALS AND METHODS: Thirty-one subjects with MetS were enrolled and randomly divided into dietary intervention group and control group. Subjects in the intervention group received three meal boxes prepared with antioxidant-rich ingredients every day for 4 weeks, and subjects in the control group maintained their usual diets. Anthropometric and various biochemical parameters related to oxidative stress, inflammation, and MetS were assessed. Brachial-ankle pulse wave velocity (baPWV) and fat measurement using computed tomography were also conducted before and after 4 weeks. RESULTS: There were significant differences in waist circumference, visceral to subcutaneous fat ratio, lipid peroxidation, oxidized low density lipoprotein (oxLDL), systolic and diastolic blood pressure, lipid parameters, advanced glycation end products, and baPWV between before and after the study in the experimental group (all p<0.05). Significant inter-group differences were observed between the experimental and control group in terms of the differences in body mass index, waist circumference, oxygen radical absorbance capacity, protein carboxylation, lipid peroxidation, oxLDL, blood pressure, lipid parameters, and baPWV between before and after the study (all p<0.05). CONCLUSION: Antioxidant-rich dietary intervention for a 4-week period ameliorated the state of oxidative stress and improved the components of MetS including central obesity, dyslipidemia, hypertension, and arterial stiffness in elderly Koreans with MetS.

Exergy Analysis of a Direct Contact Membrane Distillation (DCMD) System Based on Computational Fluid Dynamics (CFD).

Understanding the energy efficiency of direct contact membrane distillation (DCMD) is important for the widespread application and practical implementation of the process. This study analyzed the available energy, known as exergy, in a DCMD system using computational fluid dynamics (CFD). A CFD model was developed to investigate the hydrodynamic and thermal conditions in a DCMD module. After the CFD model was verified, it was used to calculate the temperature polarization coefficient (TPC) and exergy destruction magnitudes under various operating conditions. The results revealed that slight decreases and increases in the TPC occurred with distance from the inlet in the module. The TPC was found to increase as the feed temperature was reduced and the feed and permeate flow rates were increased. The exergy destruction phenomenon was more significant under higher feed temperatures and higher flux conditions. Although the most significant exergy destruction in the permeate occurred near the feed inlet, the effect became less influential closer to the feed outlet. An analysis of exergy flows revealed that the efficiency loss in the permeate side corresponded to 32.9-45.3% of total exergy destruction.

Novel FoxO1 inhibitor, JY-2, ameliorates palmitic acid-induced lipotoxicity and gluconeogenesis in a murine model.

Forkhead transcription factor forkhead box O1 (FoxO1) plays an important role in glucose and lipid metabolism, contributing to the pathogenesis of metabolic disorders. This study aimed to discover a novel FoxO1 inhibitor as a potential new anti-diabetic drug candidate, and describes the biological effects of JY-2, 5-(2,4-dichlorophenyl)-3-(pyridin-2-yl)-1,2,4-oxadiazole in vitro and in vivo. JY-2 inhibited FoxO1 transcriptional activity in a concentration-dependent manner, with an IC50 value of 22 µM. The inhibitory effects of JY-2 on FoxO3a and FoxO4 appeared to be weaker than that on FoxO1. Consistent with its inhibitory effect on FoxO1, JY-2 reduced the palmitic acid (PA)-stimulated mRNA expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes involved in gluconeogenesis in HepG2 cells. In association with the reduced expression of lipid metabolism genes, triglyceride accumulation was also reduced by JY-2, as determined by Oil Red O staining. In addition, JY-2 restored PA-impaired glucose-stimulated insulin secretion (GSIS), in conjunction with an increased mRNA expression of PDX1, MafA, and insulin in INS-1 cells. The in vivo efficacy of JY-2 was examined using C57BL/6J, db/db, and high fat-diet induced obese and diabetic (DIO) mice models, and showed that JY-2 improved glucose tolerance, in parallel with a reduced mRNA expression of gluconeogenic genes. Pharmacokinetic analysis revealed that JY-2 exhibited excellent oral bioavailability (98%), with little adverse effects. These results demonstrated that the novel FoxO1 inhibitor, JY-2, may exert beneficial anti-diabetic effects and that it warrants further investigation as a novel anti-diabetic drug candidate.

The effect of Korean Red Ginseng on sarcopenia biomarkers in type 2 diabetes patients.

BACKGROUND: The elderly population is growing rapidly worldwide and sarcopenia, which is considered as a new geriatric syndrome has become an important issue. In particular, diabetes is known to be an important risk factor for sarcopenia. In this study, we investigated the effects of Korean Red Ginseng (KRG) on biomarkers of sarcopenia in middle and old age diabetes patients. PATIENTS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in sarcopenia biomarkers at week 24. Secondary outcomes were changes in inflammatory and antioxidant markers and lean body mass at week 24. RESULTS: Fifty-nine patients completed the study. Follistatin and sex hormone binding globulin (SHBG) were significantly improved in KRG group. In the subgroup analysis, female postmenopausal patients over the age of 55 showed a significant improvement in serum SHBG, follistatin, and growth differentiation factor 15 (GDF-15) and an attenuated reduction in Troponin T (TNT) after the administration of KRG. CONCLUSION: Twenty-four week administration of KRG in diabetes patients resulted in a significant improvement in follistatin and SHBG levels, especially in old postmenopausal women. A further, larger population study with a longer follow-up period is warranted to verify and understand the effects of KRG on sarcopenia.

Circulating myokine levels in different stages of glucose intolerance.

Type 2 diabetes is the fastest growing metabolic disease in the world. Recently, muscle is considered an endocrine organ which secretes various peptides that play an important role in insulin resistance and metabolic syndrome. We assessed 4 different myokines, irisin, interleukin-13 (IL-13), follistatin-related protein-1 (FSTL-1), and fractalkine, in normal, prediabetes, and diabetes patients.A total of 126 participants who visited Gangnam Severance Hospital were enrolled and divided into normal, prediabetes, and diabetes groups based on oral glucose tolerance test and hemoglobin a1c. A cross-sectional study was conducted to measure and compare serum levels of irisin, IL-13, FSTL-1, and fractalkine among the groups.Irisin level showed a tendency to increase in prediabetes group compared to normal group (P < .1) but showed a significant decrease when comparing diabetes from prediabetes group (P < .001). IL-13 decreased in diabetes group compared to prediabetes and normal group (P < .001, P < .05, respectively). FSTL-1 of diabetes group was lower than that of prediabetes group (P < .05), and fractalkine was higher in diabetes group compared to that of prediabetes and normal group (P < .01, P < .01, respectively).Irisin, IL-13, and FSTL-1 levels were reduced in diabetes group compared to normal or prediabetes group while fractalkine showed a progressive increase from normal to diabetes group. Further studies are warranted to study the roles of various myokine in diabetes through a larger prospective study.

Supplementation with Korean Red Ginseng Improves Current Perception Threshold in Korean Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. METHODS: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. RESULTS: Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. CONCLUSION: Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.

Anti-diabetic properties of different fractions of Korean red ginseng.

ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng (KRG) has been traditionally used to treat diabetes. Ginsenosides are considered as the major bioactive components mediating anti-diabetic effects of KRG. However, considering that ginsenosides account for only about 3-4% of ginsengs, other fractions of KRG may also carry potential anti-diabetic effects. There is no study reporting the differentiated effects of ginsenosides (Spn) and non-saponin fractions (NSpn) of KRG on glycemic control. AIM OF THE STUDY: We investigated the effects of KRG, Spn, and NSpn on the indications of glycemic control and sought to elucidate physiological factors contributing their effects. MATERIALS AND METHODS: Human T2DM mimicking Nagoya-Shibata-Yasuda (NSY/hos) mice were given KRG, Spn, or NSpn admixed in rodent diet at 200 mg/kg/day for 24 weeks. Glycemic and obesity indications, blood lipid profile, systematic and local oxidative stress markers in metabolically important organs, and systematic inflammatory markers were assessed. Molecular assessments associated with glycemic control in liver and skeletal muscle were further performed. RESULTS: KRG attenuated deterioration in glucose homeostasis as evidenced by significantly lower fasting blood glucose from 22nd week and AUC during GTT at the end of the experiment compare to control. Spn enhanced insulin secretion in response to glucose stimulation and reduced protein level of glycogen phosphorylase in liver. On the other hand, NSpn ameliorated oxidative stress and inflammation. Some beneficial effects of Spn and NSpn were reflected in KRG treated mice. KRG also attenuated the accumulation of malondialdehyde in skeletal muscle and, accordingly, enhanced insulin responsiveness compare to control. CONCLUSION: Anti-diabetic properties of KRG are not solely determined by the contents of ginsenosides but the harmonic functions of its different fractions.

Use of RBC deformability index as an early marker of diabetic nephropathy.

BACKGROUND AND OBJECTIVE: Hemorheologic alterations have been suggested to play a role in the pathogenesis of diabetic microvascular complications. We measured various hemorheologic parameters and assessed their possible role as a diagnostic tool for diabetic nephropathy (DN). METHODS: 248 subjects with type 2 diabetes and 222 subjects with prediabetes were included in this study. Hemorheologic parameters, including erythrocyte sedimentation rate (ESR), elongation index at 3 Pa (EI) were measured using microfluidic hemorheometer. Various metabolic parameters were measured from fasting blood samples. The subjects were stratified into three groups according to classification of DN by urinary albumin to creatinine ratio (ACR) and four groups by estimated glomerular filtration rate (GFR), than analyzed. RESULTS: Significant differences were observed in metabolic and hemorheologic parameters according to progression of DN. Among them, (Fibrinogen×ESR)/ EI differed in all three groups of urinary ACR. In multiple regression analysis, (Fibrinogen×ESR)/ EI was an independent predictor of urine ACR after adjusted with confounding factors (ß â€Š= 0.010, p < 0.001). (Fibrinogen×ESR)/ EI also showed significant difference no or minimal CKD stage, moderate CKD and severe CKD classified by GFR. This parameter showed area under curve (AUC) of the receiver operating characteristic (ROC) curve of 0.762, and moderate sensitivity and specificity to predict prevalence of microalbuminuria. CONCLUSIONS: (Fibrinogen×ESR)/ EI is a sensitive parameter for screening diabetic nephropathy.

The relationship between cholesterol concentration and carotid intima media thickness differs according to gender and menopausal status in Korean type 2 diabetic patients.

BACKGROUND: We investigated the associations between cardiometabolic factors and carotid intima media thickness (IMT) in Korea type 2 diabetes (T2DM) patients, and assessed the possible difference with respect to gender and menopausal status. METHODS: We conducted a cross-sectional study with 1288 T2DM patients from the Department of Endocrinology and Metabolism at Gangnam Severance Hospital. Carotid IMT and various biochemical parameters were measured, and the postmenopausal status was assessed. RESULTS: In partial correlation analysis, total cholesterol (TC) and LDL cholesterol (LDL-C) were positively correlated with right maximum IMT in men. For postmenopausal women, TC and LDL-C were positively correlated with IMT (all p<0.05) while no such correlation was observed in premenopausal women. In regression analysis, age was the most predominant factor for IMT in all 3 groups. For men, insulin and TC were predictive factors for maximum IMT (all p<0.05), and for postmenopausal women, TC and LDL-C were significant factors for mean and maximum IMT (all p<0.01). However, cholesterol concentrations were not related to all types of IMT in premenopausal women. CONCLUSION: The association between LDL-C and carotid IMT seems to differ according to gender and menopausal status in T2DM patients.

The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males.

OBJECTIVE: Osteocalcin has been proposed to be a novel link between bone and energy metabolism. Previous studies showed its relations to exercise, body fat and glucose metabolism, but their interrelationship remains inconslusive. We evaluated the changes in osteocalcin level following 8-week exercise programme and assessed how they are related to concomitant changes in body fat composition, insulin resistance and various adipocytokines in a single centre, randomized and prospective design. STUDY DESIGN AND METHODS: A total of 39 young obese, otherwise healthy males were randomly assigned to control (n = 10) and exercise (n = 29) groups. Subjects in Exercise group were on 8-week supervised exercise training programme of four sessions per week. Body fat compositions were analysed using whole body bone mineral density, various metabolic parameters, osteocalcin and adipocytokines were assessed from fasting blood samples before and after 8-week exercise programme. RESULTS: Body fat reduction following exercise significantly increased serum total (1·51 ± 0·36 vs 1·69 ± 0·39 mmol/l, P = 0·01, baseline vs postexercise) and undercarboxylated osteocalcin level (0·44 ± 0·14 vs 0·64 ± 0·26 mmol/l, P < 0·01), and the increase in osteocalcin was in negative correlations with changes in body weight, BMI and body fat percentage as well as HOMA-IR and leptin (all P < 0·05). The changes in osteocalcin and leptin were not independent predictors of changes in insulin resistance and osteocalcin, respectively. CONCLUSIONS: In a physiological axis of bone-fat-energy metabolism, exercise-induced body fat reduction and improved insulin sensitivity were accompanied by an increase in serum osteocalcin and leptin levels, but other factors also seem to be involved in this interrelationship.

Effects of a structured exercise program on insulin resistance, inflammatory markers and physical fitness in obese Korean children.

Thirty-eight obese Korean children (21 boys, 17 girls), whose ages were between 9 and 15, were divided into either the intervention group (19 obese children: BMI>95P) or the age- and sex-matched obese control group. The intervention group performed an intensive exercise program under the supervision of educated instructors for 12 weeks (90 minutes/day, two days/week) and received lifestyle modification counseling using food diaries and phone calls. The control group participated in conventional counseling at an out-patient clinic. The intervention group appeared to have more improvement of body weight, body composition, serum lipid profiles and high-sensitivity C-reactive protein (hs-CRP) levels (P < 0.05) but without changes in serum adiponectin level. HOMA-IR decreased from 2.3 to 1.3 in the intervention group. Maximal oxygen consumption (VO2 max) and other physical fitness parameters were significantly improved after the intervention program (P < 0.05).

Integrative physiology: defined novel metabolic roles of osteocalcin.

The prevailing model of osteology is that bones constantly undergo a remodeling process, and that the differentiation and functions of osteoblasts are partially regulated by leptin through different central hypothalamic pathways. The finding that bone remodeling is regulated by leptin suggested possible endocrinal effects of bones on energy metabolism. Recently, a reciprocal relationship between bones and energy metabolism was determined whereby leptin influences osteoblast functions and, in turn, the osteoblast-derived protein osteocalcin influences energy metabolism. The metabolic effects of bones are caused by the release of osteocalcin into the circulation in an uncarboxylated form due to incomplete gamma-carboxylation. In this regard, the Esp gene encoding osteotesticular protein tyrosine phosphatase is particularly interesting because it may regulate gamma-carboxylation of osteocalcin. Novel metabolic roles of osteocalcin have been identified, including increased insulin secretion and sensitivity, increased energy expenditure, fat mass reduction, and mitochondrial proliferation and functional enhancement. To date, only a positive correlation between osteocalcin and energy metabolism in humans has been detected, leaving causal effects unresolved. Further research topics include: identification of the osteocalcin receptor; the nature of osteocalcin regulation in other pathways regulating metabolism; crosstalk between nutrition, osteocalcin, and energy metabolism; and potential applications in the treatment of metabolic diseases.