Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.
An imbalance in coagulation is associated with cardiovascular events. For prevention and treatment, anticoagulants, currently mainly xabans and gatrans, are used. The purpose of the present study was to provide a head-to-head comparison since there are no studies directly evaluating these novel anticoagulants. An additional aim was to find whether selected anthropological and biochemical factors can affect their anticoagulant properties as they are used in fixed doses. In this cross-sectional study, blood from 50 generally healthy donors was collected, and coagulation responses to dabigatran, argatroban, rivaroxaban, and apixaban, at a concentration of 1 μM, were analyzed. Heparin was used as a positive control. Prothrombin time (PT) expressed as international normalized ratio (INR) and activated partial thromboplastin time (aPTT) were measured and compared. Rivaroxaban was the most active according to PT/INR while argatroban according to aPTT. The ex vivo anticoagulant effect measured by INR correlated inversely with body mass index (BMI) in all four anticoagulants tested. Shortening of aPTT was associated with higher cholesterol and triglyceride levels. No sex-related differences were observed in response to the anticoagulant treatments. As this was an ex vivo study and pharmacokinetic factors were not included, the influence of BMI is of high therapeutic importance.
- MeSH
- antikoagulancia * farmakologie MeSH
- arginin * analogy a deriváty MeSH
- dabigatran farmakologie MeSH
- dospělí MeSH
- hemokoagulace * účinky léků MeSH
- index tělesné hmotnosti MeSH
- INR MeSH
- kyseliny pipekolové * farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- parciální tromboplastinový čas MeSH
- protrombinový čas MeSH
- průřezové studie MeSH
- pyrazoly farmakologie MeSH
- pyridony farmakologie farmakokinetika MeSH
- rivaroxaban * farmakologie MeSH
- sulfonamidy farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
OBJECTIVE: To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT. METHODS: Retrospective analysis was conducted of electronic medical records of KT candidates with obesity (body mass index >35 kg/m2) who underwent SG in our institution. Weight loss, adverse health events, and the listing and transplant rates were abstracted and compared with the nonsurgical cohort. RESULTS: The SG was performed in 54 patients; 50 patients did not have surgery. Baseline demographic characteristics were comparable at the time of evaluation. Mean body mass index ± SD of the SG group was 41.7±3.6 kg/m2 at baseline (vs 41.5±4.3 kg/m2 for nonsurgical controls); at 2 and 12 months after SG, it was 36.4±4.1 kg/m2 and 32.6±4.0 kg/m2 (P<.01 for both). In the median follow-up time of 15.5 months (interquartile range, 6.4 to 23.9 months), SG was followed by active listing (37/54 people), and 20 of 54 received KT during a median follow-up time of 20.9 months (interquartile range, 14.7 to 28.3 months) after SG. In contrast, 14 of 50 patients in the nonsurgical cohort were listed, and 5 received a KT (P<.01). Three patients (5.6%) experienced surgical complications. There was no difference in overall hospitalization rates and adverse health outcomes, but the SG cohort experienced a higher risk of clinically significant functional decline. CONCLUSION: In KT candidates with obesity, SG appears to be effective, with 37% of patients undergoing KT during the next 18 months (P<.01). Further research is needed to confirm and to improve the safety and efficacy of SG for patients with obesity seeking a KT.
- MeSH
- bariatrická chirurgie * metody MeSH
- chronické selhání ledvin chirurgie MeSH
- dospělí MeSH
- gastrektomie * metody škodlivé účinky MeSH
- hmotnostní úbytek * MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita * chirurgie komplikace MeSH
- retrospektivní studie MeSH
- transplantace ledvin * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Vliv autoplazmy obohacené o krevní destičky na tloušťku endometria a citlivost receptorů na estrogen a progesteron. Materiál a metody: Do této prospektivní studie bylo zařazeno 200 pacientek. Účastnice studie byly rozděleny do dvou skupin. První, kontrolní skupina dostávala hormonální substituční terapii (HRT – hormone replacement therapy). Druhá, studijní skupina dostávala intrauterinní infuzi autoplazmy obohacené o krevní destičky (PRP – platelet-rich autoplasma). Devatenáctý den menstruačního cyklu bylo provedeno ultrazvukové vyšetření s cílem zhodnotit tloušťku endometria a dále imunohistochemická analýza k stanovení citlivosti receptorů pro estrogen a progesteron. Výsledky: Během studie jsme zjistili, že po podání autoplazmy obohacené o krevní destičky se zvýšila tloušťka endometria o 0,85 mm; průměrná tloušťka endometria ve skupině na terapii PRP byla 8,25 mm (8,25–8,61 mm) a ve skupině pacientek, které dostávaly pouze HRT, byla 7,40 mm (7,34–7,65 mm). Citlivost receptorů pro estrogen se v experimentální skupině zvýšila o 3,5, přičemž v této skupině dosáhla hodnoty 75,00 (71,43–74,22) a v kontrolní skupině 71,50 (67,05–70,85). Citlivost receptorů pro progesteron se zvýšila o 9,0, hodnota v této skupině byla 95,0 (91,4–93,8) a v kontrolní skupině 86,0 (83,47–86,27). Závěr: Díky působení destičkových faktorů má terapie PRP pozitivní vliv na endometrium, kdy zvyšuje jeho tloušťku a zlepšuje receptivitu. Je tedy možné vyvodit závěr, že tato metoda zřejmě nalezne velké praktické uplatnění při zlepšování výsledků programů asistované reprodukce.
Aim: The effect of platelet-rich autoplasma on endometrial thickness and receptor sensitivity to estrogen and progesterone. Materials and methods: This prospective clinical study included 200 patients. The participants in the study were divided into two groups. The first control group received hormone replacement therapy (HRT). The second study group received an intrauterine infusion of platelet-rich autoplasma (PRP group). On the 19th day of the menstrual cycle, an ultrasound examination was performed to assess endometrial thickness, as well as an immunohistochemical analysis to determine receptor sensitivity to estrogen and progesterone. Results: In the course of the study, we found that the use of platelet-rich autoplasma increased the thickness of the endometrium by 0.85 mm; the average thickness of the endometrium in the group who received PRP therapy was 8.25 (8.25–8.61) mm; and in the group of patients who only received HRT, it was 7.40 (7.34–7.65) mm. The sensitivity of receptors to estrogen in the experimental group increased by 3.5, in the experimental group it was 75.00 (71.43–74.22), and in the control group it was 71.50 (67.05–70.85). The sensitivity of receptors to progesterone also increased by 9.0, in the experimental group it was 95.0 (91.4–93.8), and in the control group it was 86.0 (83.47–86.27). Conclusion: Due to the action of platelet factors, PRP therapy has a positive effect on the endometrium, increasing its thickness and improving its receptivity. Therefore, it can be concluded that this method can find great practical application to improve the outcomes of assisted reproductive technology programs.
- Klíčová slova
- autoplazma,
- MeSH
- dospělí MeSH
- endometrium * anatomie a histologie krevní zásobení patologie MeSH
- hormonální substituční terapie metody MeSH
- imunohistochemie MeSH
- lidé MeSH
- parenterální infuze * metody MeSH
- prospektivní studie MeSH
- statistika jako téma MeSH
- steroidní receptory MeSH
- trombocyty MeSH
- ultrasonografie MeSH
- velikost orgánu MeSH
- ženská infertilita etiologie terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
Liečba obezity je v dnešnej dobe veľkou témou. Poznáme mnoho možností liečby, pričom jej použitie sa líši na základe hodnoty BMI. Základom sú režimové opatrenia, ktorým sekundujú farmakologické a invazívne postupy. Medzi časté kontraindikácie u pacientov podstupujúcich transplantáciu obličky patrí práve obezita. Dáta v oblasti liečby obezity potencionálneho darcu obličky sú nedostatočné. V našej práci prezentujeme prípad 63-ročnej pacientky, ktorú sme úspešne liečili GLP1-receptorovým agonistom a môže byť darcom obličky.
Obesity treatment is a big topic nowadays. Many treatment options are known, and their use varies based on BMI. Regimen measures are the mainstay, followed by pharmacological and invasive procedures. Obesity is one of the common contraindications in patients undergoing kidney transplantation. Data in the treatment of obesity in the potential kidney donor are scarce. We present the case of a 63-year-old female patient who was successfully treated with a GLP-1 receptor agonist and may be a kidney donor.
- MeSH
- dárci tkání MeSH
- index tělesné hmotnosti MeSH
- látky proti obezitě aplikace a dávkování terapeutické užití MeSH
- léčba obezity MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita * metabolismus terapie MeSH
- receptor pro glukagonu podobný peptid 1 agonisté aplikace a dávkování terapeutické užití MeSH
- transplantace ledvin MeSH
- žijící dárci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Chuť i míra hladu, ale i rychlost metabolizmu jsou geneticky determinovány a regulace probíhá na třech úrovních v mozku a také ve střevě, a to pomocí střevních hormonů a neuromodulátorů. Hubnutí není fyziologický proces, tělo je nastaveno tak, že bychom měli neustále přibírat až na hmotnost, která je nám zřejmě geneticky předurčena. Poslední roky se objevují nové moderní a velmi bezpečné léky na hubnutí a na léčbu obezity jako nemoci. Začíná převládat názor, že obezitu je třeba léčit doživotně, za pomoci nejen změny životního stylu, ale také za použití léků nebo postupů bariatrické chirurgie.
Appetite and hunger, as well as metabolic rate, are genetically determined and regulated at three levels in the brain and also in the bowel by bowel hormones and neuromodulators. Weight loss is not a physiological process, the body is set up to enable continuous weigh gaining up to the weight that is probably genetically predetermined for us. In recent years, new modern and very safe drugs are emerging for weight loss and for treating obesity as a disease. The opinion that obesity should be treated for life, not only with lifestyle changes but also with drugs or bariatric surgery procedures, is becoming predominant.
- MeSH
- bupropion terapeutické užití MeSH
- fentermin terapeutické užití MeSH
- glukagonu podobný peptid 1 terapeutické užití MeSH
- látky proti obezitě aplikace a dávkování terapeutické užití MeSH
- liraglutid terapeutické užití MeSH
- nadváha etiologie farmakoterapie genetika psychologie terapie MeSH
- naltrexon terapeutické užití MeSH
- obezita etiologie farmakoterapie genetika psychologie terapie MeSH
- orlistat terapeutické užití MeSH
- MeSH
- energetický příjem MeSH
- kalorická restrikce MeSH
- nadváha prevence a kontrola terapie MeSH
- obezita prevence a kontrola terapie MeSH
- optimální tělesná hmotnost fyziologie MeSH
- redukční dieta metody trendy MeSH
- výživové doporučené dávky MeSH
- změny tělesné hmotnosti MeSH
- Publikační typ
- hodnotící studie MeSH
Exposures to social and environmental stressors arise individual behavioural response and thus indirectly affect cardiometabolic health. The aim of this study was to investigate several social and environmental stressors and the paths of their influence on cardiometabolic health. The data of 2154 participants (aged 25-64 years) from the cross-sectional population-based study were analysed. The composite score of metabolic disorders (MS score) was calculated based on 5 biomarkers: waist circumference, blood pressure, fasting blood glucose, HDL-cholesterol, triglycerides. The effects of social stressors (education level, income), environmental stressors (NO2, noise) and behavioural factors (unhealthy diet, smoking, alcohol consumption, sedentary behaviours) on MS score were assessed using a structural model. We observed a direct effect of education on MS score, as well as an indirect effect mediated via an unhealthy diet, smoking, and sedentary behaviours. We also observed a significant indirect effect of income via sedentary behaviours. The only environmental stressor predicting MS was noise, which also mediated the effect of education. In summary, the effect of social stressors on the development of cardiometabolic risk had a higher magnitude than the effect of the assessed environmental factors. Social stressors lead to an individual's unhealthy behaviour and might predispose individuals to higher levels of environmental stressors exposures.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- HDL-cholesterol krev MeSH
- kardiovaskulární nemoci etiologie epidemiologie MeSH
- kouření škodlivé účinky MeSH
- krevní glukóza metabolismus MeSH
- krevní tlak MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolické nemoci etiologie epidemiologie MeSH
- obvod pasu MeSH
- průřezové studie MeSH
- psychický stres MeSH
- rizikové faktory MeSH
- sedavý životní styl * MeSH
- triglyceridy krev MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Growing evidence supports the important role of 24-hour movement behaviours (MB) in preventing childhood obesity. However, research to understand the heterogeneity and variability of MB among individuals and what kind of typologies of individuals are at risk of developing obesity is lacking. To bridge this gap, this study identified typologies of 24-hour MB in children and adolescents and investigated their associations with adiposity indicators. METHODS: In this cross-sectional study, 374 children and 317 adolescents from the Czech Republic wore wrist-worn accelerometers for seven consecutive days. Time spent in moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour (SB), and sleep was quantified using raw accelerometery data. Adiposity indicators included body mass index (BMI) z-score, fat mass percentage (FM%), fat mass index (FMI), and visceral adipose tissue (VAT). Bias-adjusted latent profile analysis was used on the 24-hour MB data to identify MB typologies and their associations with adiposity indicators. The models were adjusted for potential confounders. The identified typologies were labelled to reflect the behavioural profiles of bees to aid interpretability for the general public. RESULTS: Two typologies were identified in children: highly active Workers characterised by high levels of MVPA and LPA, and inactive Queens characterised by low levels of MVPA and LPA, high levels of SB and longer sleep duration compared to Workers. In adolescents, an additional typology labelled as Drones was characterised by median levels of MVPA, LPA, SB and longest sleep duration. After controlling for covariates, we found that children labelled as Queens were associated with 1.38 times higher FM%, 1.43 times higher FMI, and 1.67 times higher VAT than Workers. In adolescents, Drones had 1.14 times higher FM% and Queens had 1.36 higher VAT in comparison with Workers, respectively. CONCLUSION: Our study highlights the importance of promoting active lifestyles in children and adolescents to potentially reduce adiposity. These findings can provide insights for interventions aimed at promoting healthy MB and preventing childhood obesity.
- MeSH
- adipozita * fyziologie MeSH
- akcelerometrie MeSH
- cvičení * MeSH
- dítě MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- mladiství MeSH
- obezita dětí a dospívajících * epidemiologie MeSH
- průřezové studie MeSH
- sedavý životní styl * MeSH
- spánek fyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Antipsychotics are indispensable in the treatment of severe mental illneses, however adverse metabolic effects including diabetes, weight gain, dyslipidemia, and related cardiovascular morbidity are common, and current pharmacological strategies for their management are unsatisfactory. Glucagon-like 1 peptide receptor agonists (GLP-1 RAs) are approved for the treatment of type 2 diabetes and obesity hold promise for the management of antipsychotic-associated adverse metabolic effects. METHODS: To characterize the molecular effects and identify biomarkers for GLP-1 RA preventive treatment, Sprague-Dawley female rats were treated with long-acting formulations of the antipsychotic olanzapine and the GLP-1 RA dulaglutide for 8 days. A pair-feeding protocol evaluated the combined effects of dulaglutide and food restriction on an olanzapine-induced metabolic phenotype. Body weight and food consumption were recorded. Biochemical analysis included a lipid profile, a spectrum of gastrointestinal and adipose tissue-derived hormones, and fibroblast growth factor 21 serum levels. RESULTS: Olanzapine induced hyperphagia, weight gain, increased serum triglycerides and HDL cholesterol. Food restriction affected the OLA-induced phenotype but not serum markers. Dulaglutide led to a modest decrease in food intake, with no effect on weight gain, and did not reverse the OLA-induced changes in serum lipid parameters. Concomitant dulaglutide and food restriction resulted in weight loss, decreased feed efficiency, and lower total and HDL cholesterol. CONCLUSIONS: A combined strategy of dulaglutide and food restriction manifested a massive synergistic benefit. GLP-1RAs represent a promising strategy and deserve thorough future research. Our findings underline the potential importance of lifestyle intervention in addition to GLP-1 RA treatment.
- MeSH
- antipsychotika farmakologie škodlivé účinky MeSH
- benzodiazepiny farmakologie škodlivé účinky MeSH
- glukagonu podobné peptidy * analogy a deriváty farmakologie MeSH
- hmotnostní přírůstek účinky léků MeSH
- imunoglobuliny - Fc fragmenty * farmakologie MeSH
- kalorická restrikce metody MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- olanzapin * farmakologie škodlivé účinky MeSH
- potkani Sprague-Dawley * MeSH
- přijímání potravy účinky léků MeSH
- receptor pro glukagonu podobný peptid 1 agonisté metabolismus MeSH
- rekombinantní fúzní proteiny * farmakologie MeSH
- tělesná hmotnost účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
