RÉSUMÉ
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here. METHODS: Healthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing. RESULTS: Increased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (- 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray-Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats. CONCLUSIONS: In the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities.
Sujet(s)
Modèles animaux de maladie humaine , Évolution de la maladie , Microbiome gastro-intestinal , Défaillance cardiaque , Méthylamines , Débit systolique , Fonction ventriculaire gauche , Animaux , Défaillance cardiaque/physiopathologie , Défaillance cardiaque/microbiologie , Défaillance cardiaque/métabolisme , Méthylamines/métabolisme , Méthylamines/sang , Mâle , Obésité/microbiologie , Obésité/physiopathologie , Obésité/métabolisme , Oxygénases/métabolisme , Oxygénases/génétique , Foie/métabolisme , Marqueurs biologiques/sang , Fèces/microbiologie , Rats , Muqueuse intestinale/métabolisme , Muqueuse intestinale/microbiologie , Bactéries/métabolisme , DysbioseRÉSUMÉ
BACKGROUND: Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity. METHODS AND RESULTS: In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). CONCLUSIONS: We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.
Sujet(s)
Études croisées , Avant-bras , Insuline , Microcirculation , Obésité , Phentolamine , Débit sanguin régional , Système nerveux sympathique , Vasodilatation , Humains , Avant-bras/vascularisation , Mâle , Phentolamine/pharmacologie , Femelle , Obésité/physiopathologie , Vasodilatation/effets des médicaments et des substances chimiques , Vasodilatation/physiologie , Adulte , Système nerveux sympathique/physiopathologie , Système nerveux sympathique/effets des médicaments et des substances chimiques , Débit sanguin régional/effets des médicaments et des substances chimiques , Microcirculation/effets des médicaments et des substances chimiques , Vitesse du flux sanguin , Adulte d'âge moyen , Technique du clamp glycémique , Insulinorésistance , Bloc anesthésique du système nerveux autonome/méthodesRÉSUMÉ
Almost 90% of patients with type 2 diabetes mellitus (DM2) are obese. Obesity increases the risk of developing DM2 several times. The calculation of anthropometric indices is used to diagnose the severity of obesity, as well as to assess the risk associated with obesity. The aim of the study is to study the relationship between Body Mass Index (BMI), waist circumference to hip circumference ratio (waist-to-hip ratio, WC/HR), Body Roundness Index (BRI) and Visceral Adiposity Index (VAI) with the risk of hypoglycemia in elderly and senile patients with DM2. The study included 122 elderly and senile patients (mean age 71±6,18 years) with DM2. The study participants were divided into 2 groups: patients with cases of hypoglycemia (n=65) and patients without a history of hypoglycemia (n=57). We have found that lower BMI, WC/HR, BRI, and VAI values are significantly associated with an increased risk of hypoglycemia in patients with DM2 of older age groups.
Sujet(s)
Indice de masse corporelle , Diabète de type 2 , Hypoglycémie , Obésité , Humains , Diabète de type 2/complications , Diabète de type 2/épidémiologie , Hypoglycémie/épidémiologie , Hypoglycémie/diagnostic , Hypoglycémie/étiologie , Sujet âgé , Mâle , Femelle , Obésité/complications , Obésité/épidémiologie , Obésité/physiopathologie , Tour de taille/physiologie , Facteurs de risque , Anthropométrie/méthodes , Rapport taille-hanches , Sujet âgé de 80 ans ou plus , Russie/épidémiologieRÉSUMÉ
The STEP-HFpEF DM trial1 showed that semaglutide improved body weight, systemic inflammation, and heart failure symptoms in people with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. By addressing both metabolic and cardiovascular risk, semaglutide is a promising therapeutic option for HFpEF in addition to SGLT2i.
Sujet(s)
Diabète de type 2 , Peptides glucagon-like , Défaillance cardiaque , Obésité , Débit systolique , Humains , Obésité/traitement médicamenteux , Obésité/physiopathologie , Diabète de type 2/traitement médicamenteux , Défaillance cardiaque/traitement médicamenteux , Défaillance cardiaque/physiopathologie , Débit systolique/effets des médicaments et des substances chimiques , Peptides glucagon-like/usage thérapeutique , Peptides glucagon-like/pharmacologie , Inhibiteurs du cotransporteur sodium-glucose de type 2/usage thérapeutique , Inhibiteurs du cotransporteur sodium-glucose de type 2/pharmacologieRÉSUMÉ
BACKGROUND: Exercise is known to provide multiple metabolic benefits such as improved insulin sensitivity and glucose control in individuals with type 2 diabetes mellitus (T2DM) and those at risk. Beyond the traditional exercise dose, exercise timing is perceived as a contemporary hot topic, especially in the field of T2DM; however, the number of intervention studies assessing exercise timing and glucose metabolism is scarce. Our aim is to test the effect of exercise timing (i.e., morning, afternoon, or evening) on the inter-individual response variability in glycemic control and related metabolic health parameters in individuals with T2DM and those at risk during a 12-week intervention. METHODS: A randomized crossover exercise intervention will be conducted involving two groups: group 1, individuals with T2DM; group 2, age-matched older adults with overweight/obesity. The intervention will consist of three 2-week blocks of supervised post-prandial exercise using high-intensity interval training (HIIT). Between each training block, a 2-week washout period, where participants avoid structured exercise, will take place. Assessments will be conducted in both groups before and after each exercise block. The primary outcomes include the 24-h area under the curve continuous glucose monitoring-based glucose. The secondary outcomes include body composition, resting energy expenditure, insulin response to a meal tolerance test, maximal aerobic capacity, peak power output, physical activity, sleep quality, and insulin and glucose levels. All primary and secondary outcomes will be measured at each assessment point. DISCUSSION: Outcomes from this trial will provide us additional insight into the role of exercise timing on the inter-individual response variability in glycemic control and other related metabolic parameters in two distinct populations, thus contributing to the development of more effective exercise prescription guidelines for individuals with T2DM and those at risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT06136013. Registered on November 18, 2023.
Sujet(s)
Glycémie , Études croisées , Diabète de type 2 , Entrainement fractionné de haute intensité , Obésité , Essais contrôlés randomisés comme sujet , Humains , Diabète de type 2/sang , Diabète de type 2/thérapie , Diabète de type 2/physiopathologie , Obésité/thérapie , Obésité/physiopathologie , Obésité/sang , Glycémie/métabolisme , Facteurs temps , Entrainement fractionné de haute intensité/méthodes , Horloges circadiennes , Adulte d'âge moyen , Mâle , Femelle , Surpoids/thérapie , Surpoids/physiopathologie , Traitement par les exercices physiques/méthodes , Résultat thérapeutique , Sujet âgé , Régulation de la glycémie/méthodes , Exercice physiqueRÉSUMÉ
Heart failure (HF) is a major health issue, affecting up to 2% of the adult population worldwide. Given the increasing prevalence of obesity and its association with various cardiovascular diseases, understanding its role in HFrEF outcomes is crucial. This study aimed to investigate the impact of obesity on in-hospital mortality and prolonged hospital stay in patients with heart failure with reduced ejection fraction (HFrEF). We conducted a retrospective analysis of 425 patients admitted to the cardiology unit at the University Clinical Hospital in Wroclaw, Poland, between August 2018 and August 2020. Statistical analyses were performed to evaluate the interactions between BMI, sex, and comorbidities on in-hospital mortality. Significant interactions were found between sex and BMI as well as between BMI and post-stroke status, affecting in-hospital mortality. Specifically, increased BMI was associated with decreased odds of in-hospital mortality in males (OR = 0.72, 95% CI: 0.55-0.94, p < 0.05) but higher odds in females (OR = 1.18, 95% CI: 0.98-1.42, p = 0.08). For patients without a history of stroke, increased BMI reduced mortality odds (HR = 0.78, 95% CI: 0.64-0.95, p < 0.01), whereas the effect was less pronounced in those with a history of stroke (HR = 0.89, 95% CI: 0.76-1.04, p = 0.12). In conclusion, the odds of in-hospital mortality decreased significantly with each 10% increase in BMI for males, whereas for females, a higher BMI was associated with increased odds of death. Additionally, BMI reduced in-hospital mortality odds more in patients without a history of cerebral stroke (CS) compared to those with a history of CS. These findings should be interpreted with caution due to the low number of observed outcomes and potential interactions with BMI and sex.
Sujet(s)
Indice de masse corporelle , Défaillance cardiaque , Mortalité hospitalière , Obésité , Débit systolique , Humains , Mâle , Femelle , Défaillance cardiaque/mortalité , Défaillance cardiaque/physiopathologie , Sujet âgé , Études rétrospectives , Adulte d'âge moyen , Obésité/complications , Obésité/physiopathologie , Obésité/épidémiologie , Durée du séjour/statistiques et données numériques , Sujet âgé de 80 ans ou plus , Pologne/épidémiologie , Facteurs de risque , Facteurs sexuels , Comorbidité , Accident vasculaire cérébral/mortalité , Accident vasculaire cérébral/épidémiologieRÉSUMÉ
BACKGROUND: Obesity has been linked to arterial stiffness, while no consensus was reached on the association. We aimed to clarify the association of general and central obesity with arterial stiffness by combining observational studies and Mendelian randomization (MR) study. METHODS: Two cross-sectional studies were performed in UK Biobank and Fuqing Cohort, respectively. Two-sample MR study was conducted using summary data of GWASs from GIANT consortium and UK Biobank. General obesity and central obesity were measured using body mass index (BMI) and waist circumference (WC), respectively. Arterial stiffness was measured by arterial stiffness index (ASI) in UK Biobank or branchial-ankle pulse wave velocity (baPWV) in Fuqing Cohort. RESULTS: Two observational studies found a consistent positive association of BMI and WC with arterial stiffness when adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and LDL cholesterol. However, when additionally adjusting for metabolic traits (i.e., systolic blood pressure, diastolic blood pressure, blood glucose, triglycerides, high-density lipoprotein cholesterol, and WC or BMI), the association with BMI changed to be inverse. As compared to the lowest quintile group, the adjusted ORs across groups of second to fifth quintile were 0.93, 0.90, 0.83, and 0.72 in UK Biobank and 0.88, 0.65, 0.63, and 0.50 in Fuqing Cohort. In contrast, the positive relationship with WC remained stable with the adjusted ORs of 1.23, 1.46, 1.60, and 1.56 in UK Biobank and 1.35, 1.44, 1.77, and 1.64 in Fuqing Cohort. MR analyses provided supportive evidence of the negative association with BMI (OR = 0.97, 95%CI = 0.94-1.00) and the positive association with WC (OR = 1.14, 95%CI = 1.08-1.20). CONCLUSIONS: Observational and genetic analyses provide concordant results that central obesity is independently related to arterial stiffness, while the role of general obesity depends on metabolic status.
Sujet(s)
Indice de masse corporelle , Analyse de randomisation mendélienne , Obésité abdominale , Obésité , Rigidité vasculaire , Humains , Rigidité vasculaire/physiologie , Mâle , Femelle , Adulte d'âge moyen , Études transversales , Obésité abdominale/épidémiologie , Obésité abdominale/physiopathologie , Obésité/épidémiologie , Obésité/physiopathologie , Adulte , Tour de taille , Sujet âgé , Royaume-Uni/épidémiologie , Analyse de l'onde de pouls , Études de cohortesRÉSUMÉ
INTRODUCTION: The prevalence of overweight and obesity has increased dramatically. At the same time, lack of sleep has become a part of the modern lifestyle, as well as shift and night work. As a result, chronodisruption, i. e. a change in physiological processes that are controlled by the internal clock, becomes commonplace. Epidemiological data show that too short but also too long sleep are associated with an increased risk of obesity, also seen for night shift work. Overweight and obesity are associated with metabolic syndrome and data likewise report an increased risk by both short and long sleep. It has not yet been conclusively clarified how chronodisruption influences the metabolic risks. Clinical experimental studies report on neuroendocrine and circadian mechanisms and it has been shown that lack of sleep increases the hunger-promoting hormone ghrelin as well as subjective feelings of hunger and increases leptin levels. Lack of sleep also increases hedonic hunger and food-related reward signals. Through preventive measures, chronodisruption and thus, the risk of obesity can be counteracted. The extent to which smartwatches and fitness trackers, which according to the manufacturer can measure and analyze sleep, provide an objective picture of sleep has not been sufficiently investigated. However, smartwatches and fitness trackers can - probably - increase awareness of sleep in the modern society.
Sujet(s)
Obésité , Humains , Obésité/physiopathologie , Privation de sommeil/physiopathologie , Rythme circadien/physiologie , Syndrome métabolique X/physiopathologie , Métabolisme énergétique/physiologie , Poids/physiologie , Facteurs de risque , Horaire de travail posté/effets indésirables , Troubles du rythme circadien du sommeil/physiopathologieRÉSUMÉ
INTRODUCTION: The obesity epidemic has led to an increased prevalence of obesity-related glomerulopathy (ORG). This disease is characte-rized by proteinuria, glomerulomegaly, progressive glomerulosclerosis and a decline in renal function. Individuals with obesity frequently display arterial hypertension and diabetes mellitus, exacerbating renal damage. The pathogenesis involves overactivation of the RAAS (Renin-Angiotensin-Aldosterone System), glomerular hyperfiltration, an inflammatory state with oxidative stress, hyperinsulinemia-induced hemodynamic alterations and lipotoxicity. Additionally, obesity represents a significant risk factor for kidney stone formation, further contributing to renal damage. The management of obesity-induced nephropathy primarily involves weight reduction strategies and optimized control of blood pressure and metabolic factors. Early detection is crucial to counteract the progression of kidney disease. Noteworthy, obesity significantly complicates the implementation of renal replacement procedures, including kidney transplantation, and increases the rate of complications. In summary, there are many reasons why obesity should gain attention in the field of nephrology.
Sujet(s)
Obésité , Obésité/complications , Obésité/physiopathologie , Humains , Facteurs de risque , Maladies du rein/physiopathologie , Maladies du rein/étiologie , Maladies du rein/thérapie , Comorbidité , Études transversalesRÉSUMÉ
INTRODUCTION: Individuals with obesity who undergo surgical or pharmacological therapies achieve good results in terms of weight and cardiometabolic risk reduction. It is not uncommon for those affected to equate the extent of weight loss achieved, with long-term treatment success. What is overlooked is that, in addition to obesity, significant weight loss also carries a risk of sarcopenia. Sarcopenic obesity and sarcopenia, in turn, increase the risk of cardiometabolic diseases. Physical activity has the potential to counteract cardiometabolic disease risk caused by obesity and sarcopenia. The underlying mechanism is contained in the endocrine organ skeletal muscle. The production and release of myokines in particular counteracts sarcopenic obesity and its complications. Physical activity is required to initiate myokine production. Endurance and strength training proves to be an effective training combination. In order to achieve a sustainable cardiometabolic risk reduction, the objectives and timing of physical activity should therefore be divided into two phases, a preparatory phase and an actual weight loss phase.
Sujet(s)
Exercice physique , Obésité , Sarcopénie , Humains , Obésité/physiopathologie , Obésité/thérapie , Obésité/complications , Sarcopénie/prévention et contrôle , Sarcopénie/thérapie , Sarcopénie/physiopathologie , Exercice physique/physiologie , Perte de poids/physiologie , Muscles squelettiques/physiopathologie , Maladies cardiovasculaires/prévention et contrôleRÉSUMÉ
The aim of this study is to investigate circadian rhythms in independently living adults with obesity and mental disease, exploring the interplay between biological markers and lifestyle factors. Eighty participants divided equally into four groups; (i) people with obesity and schizophrenia; (ii) people with obesity and bipolar disorder; (iii) people with obesity without mental disease or sleep disorders, and (iv) people without obesity, mental disease or sleep disorders. Over two consecutive days, participants engage in repeated self-sampling of hair follicle and saliva; concurrently, data is collected on diet, body temperature, light exposure, sleep parameters, and physical activity by accelerometry. Hair follicles are analyzed for circadian gene expression, saliva samples for cortisol and melatonin concentrations. Circadian rhythms are investigated by cosinor analysis. The study employs a participant-tailored sampling schedule to minimize disruptions to daily routine and enhance ecological validity. The methodology aims to provide a comprehensive insight into the factors contributing to circadian disruptions in people with obesity, bipolar disorder and schizophrenia, potentially informing strategies for future management and mitigation. Trial registration: (ClinicalTrials.gov Identifier: NCT05413486).
Sujet(s)
Trouble bipolaire , Rythme circadien , Mode de vie , Obésité , Schizophrénie , Humains , Trouble bipolaire/physiopathologie , Obésité/physiopathologie , Schizophrénie/physiopathologie , Adulte , Rythme circadien/physiologie , Femelle , Mâle , Salive/métabolisme , Salive/composition chimique , Adulte d'âge moyen , Hydrocortisone/métabolisme , Hydrocortisone/analyse , Mélatonine/métabolismeSujet(s)
Pression sanguine , Indice de masse corporelle , Humains , Enfant , Mâle , Adolescent , Femelle , Hongrie , Pression sanguine/physiologie , Valeurs de référence , Études transversales , Surpoids/physiopathologie , Mesure de la pression artérielle/méthodes , Enfant d'âge préscolaire , Jeune adulte , Artère brachiale/physiopathologie , Obésité/physiopathologie , Obésité pédiatrique/physiopathologieRÉSUMÉ
Konjac glucomannan (KGM), high-viscosity dietary fiber, is utilized in weight management. Previous investigations on the appetite-suppressing effects of KGM have centered on intestinal responses to nutrients and gastric emptying rates, with less focus on downstream hypothalamic neurons of satiety hormones. In our studies, the molecular mechanisms through which KGM and its degradation products influence energy homeostasis via the adipocyte-hypothalamic axis have been examined. It was found that high-viscosity KGM more effectively stimulates enteroendocrine cells to release glucagon-like peptide-1 (GLP-1) and reduces ghrelin production, thereby activating hypothalamic neurons and moderating short-term satiety. Conversely, low-viscosity DKGM has been shown to exhibit stronger anti-inflammatory properties in the hypothalamus, enhancing hormone sensitivity and lowering the satiety threshold. Notably, both KGM and DKGM significantly reduced leptin signaling and fatty acid signaling in adipose tissue and activated brown adipose tissue thermogenesis to suppress pro-opiomelanocortin (POMC) expression and activate agouti-related protein (AgRP) expression, thereby reducing food intake and increasing energy expenditure. Additionally, high-viscosity KGM has been found to activate the adipocyte-hypothalamus axis more effectively than DKGM, thereby promoting greater daily energy expenditure. These findings provide novel insights into the adipocyte-hypothalamic axis for KGM to suppress appetite and reduce weight.
Sujet(s)
Adipocytes , Régulation de l'appétit , Alimentation riche en graisse , Métabolisme énergétique , Hypothalamus , Souris de lignée C57BL , Animaux , Souris , Métabolisme énergétique/effets des médicaments et des substances chimiques , Hypothalamus/métabolisme , Hypothalamus/effets des médicaments et des substances chimiques , Alimentation riche en graisse/effets indésirables , Mâle , Régulation de l'appétit/effets des médicaments et des substances chimiques , Adipocytes/métabolisme , Adipocytes/effets des médicaments et des substances chimiques , Humains , Glucagon-like peptide 1/métabolisme , Ghréline/métabolisme , Leptine/métabolisme , Protéine apparentée à Agouti/métabolisme , Protéine apparentée à Agouti/génétique , Thermogenèse/effets des médicaments et des substances chimiques , Pro-opiomélanocortine/métabolisme , Pro-opiomélanocortine/génétique , Obésité/métabolisme , Obésité/physiopathologie , Obésité/diétothérapie , MannanesRÉSUMÉ
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.
Sujet(s)
Modèles animaux de maladie humaine , Défaillance cardiaque , Myocytes cardiaques , Débit systolique , Animaux , Humains , Mâle , Rats , Protéines du cycle cellulaire/métabolisme , Protéines du cycle cellulaire/antagonistes et inhibiteurs , Diastole/effets des médicaments et des substances chimiques , Défaillance cardiaque/traitement médicamenteux , Défaillance cardiaque/physiopathologie , Défaillance cardiaque/anatomopathologie , Myocarde/anatomopathologie , Myocarde/métabolisme , Myocytes cardiaques/effets des médicaments et des substances chimiques , Myocytes cardiaques/métabolisme , Obésité/traitement médicamenteux , Obésité/physiopathologie , Rats de lignée WKY , Débit systolique/effets des médicaments et des substances chimiques , Tubuline/métabolismeRÉSUMÉ
Obesity is often associated with a chronic, low-grade inflammatory state affecting the entire body. This sustained inflammatory state disrupts the coordinated communication between the periphery and the brain, which has a crucial role in maintaining homeostasis through humoural, nutrient-mediated, immune and nervous signalling pathways. The inflammatory changes induced by obesity specifically affect communication interfaces, including the blood-brain barrier, glymphatic system and meninges. Consequently, brain areas near the third ventricle, including the hypothalamus and other cognition-relevant regions, become susceptible to impairments, resulting in energy homeostasis dysregulation and an elevated risk of cognitive impairments such as Alzheimer's disease and dementia. This Review explores the intricate communication between the brain and the periphery, highlighting the effect of obesity-induced inflammation on brain function.
Sujet(s)
Encéphale , Inflammation , Obésité , Humains , Obésité/complications , Obésité/physiopathologie , Obésité/métabolisme , Encéphale/métabolisme , Encéphale/anatomopathologie , Animaux , Barrière hémato-encéphalique/métabolisme , Système glymphatique/physiopathologie , HoméostasieRÉSUMÉ
BACKGROUND: Individuals who are living with obesity often adopt alternative lower limb walking mechanics compared to persons with a healthy weight. Stair negotiation is a common activity of daily living that, when used consistently with diet and other physical activity, can help promote the reversal of health-related risk factors associated with people who are obese. The purpose of this study was to determine how stair negotiation affects normalized and non-normalized peak knee extension and abduction moments in young adults who live with obesity (BMI between 30 and 40 kg/m2) compared to adults with a healthy weight (BMI between 18.5 and 25 kg/m2). METHODS: Fifteen young adults living with obesity and fifteen with a healthy weight performed stair ascent and descent walking trials on a 3-step instrumented staircase at a self-selected walking speed. A one-way ANCOVA (covariate: gait speed) was used to compare knee moment variables between groups. RESULTS: No significant differences were found between groups in peak knee joint moments normalized to body mass. The individuals living with obesity demonstrated significantly larger non-normalized peak knee extension moments during stair ascent and descent but no differences in the non-normalized peak knee abduction moments for stair ascent or descent. CONCLUSION: Results of this study indicate differences in non-normalized peak knee extension moments between BMI groups. The young age of the obese group may have contributed to minimal differences overall. Future research should determine how these findings differ in an older obese population and how using a handrail would affect these results.
Sujet(s)
Articulation du genou , Obésité , Humains , Mâle , Femelle , Obésité/physiopathologie , Articulation du genou/physiopathologie , Adulte , Jeune adulte , Montée d'escalier/physiologie , Phénomènes biomécaniques , Amplitude articulaire/physiologie , Indice de masse corporelle , Démarche/physiologie , Marche à pied/physiologieRÉSUMÉ
Background: There is increasing awareness of the physiological effects of Ramadan intermittent fasting (RIF) in obese subjects. However, there are no data on the effects of RIF on plasma volume changes (ΔPV) in individuals with different body weights. Background and Objectives: This study investigated the effects of RIF on ΔPV in normal-weight (NW) and overweight (OW) adult men, and adult men with obesity (OB) and severe obesity (SO). Materials and Methods: Thirty-two male subjects (32) were divided into four groups (n = 8 per group) according to their body mass index (BMI): normal weight (NW) (BMI < 25 kg/m2; age = 27.4 ± 3.8), overweight (OW) (BMI between 25 and 29.9 kg/m2; age = 26.8 ± 3.7), obese subjects (OB) (BMI between 30 and 34.9 kg/m2; age = 25.6 ± 2.9), and severely obesity (SO) (BMI between 35 and 40 kg/m2; age = 24.0 ± 4.1). Blood samples were collected for 24 h on 4 different occasions, at T0 before the start of the Ramadan month, at T1 15 days after the start of Ramadan, at T2 one day after the end of Ramadan, and at T3 on the 21st day after the end of Ramadan to determine ΔPV. All groups completed their fasting rituals for the 30 days of Ramadan. Results: A significant group × time effect occurred for body mass (p = 0.001; ES = 0.53), BMI (p = 0.001; ES = 0.53), and body fat percentage (p = 0.001; ES = 0.52). Post hoc tests indicated reductions in body mass in OB and SO at T1 (p = 0.03; ES = 0.21 and p = 0.002; ES = 0.12) and T2 (p = 0.03; ES = 0.31 and p = 0.02; ES = 0.23), reductions in BMI in OB and SO at T1 (p = 0.04; ES = 0.35 and p = 0.03; ES = 0.42) and T2 (p = 0.03; ES = 0.52 and p = 0.005; ES = 0.48), and reductions in body fat percentage only in OB AT T1 (p = 0.002; ES = 0.31) and T2 (p = 0.001; ES = 0.17). A significant group × time effect occurred for hematocrit (p = 0.02; ES = 0.34), hemoglobin (p = 0.01; ES = 0.35), and ΔPV (p = 0.02; ES = 0.18). Post hoc tests indicated increases in hematocrit in OB at T2 (p = 0.03; ES = 0.36) and hemoglobin in OB and SO at T1 (p = 0.03; ES = 0.35 and p = 0.002; ES = 0.32) and T2 (p = 0.003; ES = 0.21 and p = 0.002; ES = 0.33). There were also increases in ΔPV in OB at T1 and T2 (p = 0.002; ES = 0.25 and p = 0.003; ES = 0.22) and in SO only at T2 (p = 0.02; ES = 0.37). Contrast analysis indicated that NW was significantly lower than the grand mean of OW, Ob, and SO for all anthropometric and PVV variables (all p < 0.05). Conclusions: The effects of RIF on ΔPV and anthropometric characters was greater in obese individuals compared to normal-weight and overweight participants, suggesting that the improvements in body composition and ΔPV produced by RIF could positively influence obesity.
Sujet(s)
Indice de masse corporelle , Poids , Jeûne , Islam , Volume plasmatique , Humains , Mâle , Jeûne/physiologie , Adulte , Volume plasmatique/physiologie , Poids/physiologie , Obésité/physiopathologie , Obésité/complications , Surpoids/complications , Surpoids/physiopathologie , Jeûne intermittentRÉSUMÉ
BACKGROUND: Physical activity has shown beneficial effects for a good state of muscles in aging, but the specific activities of daily living that could be protective remains unclear. This study aimed to analyse the associations of different pattern-recognition-measured daily activities with sarcopenia and sarcopenic obesity in a sample of older adults. METHODS: 200 community-dwelling older adults wore the Intelligent Device for Energy Expenditure and Activity for two consecutive days. Twelve major daily activities recorded were merged in to three common intensity categories: sedentary behaviour (SB), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). For physical performance measurements included, hand grip dynamometer and chair-stand tests were used. Skeletal muscle mass and fat mass were estimated by bioelectrical impedance analysis. Associations of daily activities with the study variables were examined using linear regression models. RESULTS: There were no significant associations between total time spent in SB, LPA, or MVPA and sarcopenia. Sarcopenic obesity showed a negative association with total time spent in MVPA [ß (95%CI): -0.29 (-0.41, -0.17)]. Walk at a brisk pace was significatively associated with lower limb physical performance, muscle mass and fat mass % [ß (95%CI): 1.15 (0.40, 1.91); 1.45 (0.68, 2.22) and -2.63 (-4.12, -1.14) respectively]. Other MVPA activities were also significatively associated with the same sarcopenic obesity components [ß (95%CI): 4.65 (0.55, 8.75); 8.59 (4.51, 12.67) and -13.98 (-21.96, -5.99) respectively]. CONCLUSION: Time spent in daily activities of moderate-to-vigorous intensity is negatively associated with sarcopenic obesity but not with sarcopenia.
Sujet(s)
Activités de la vie quotidienne , Exercice physique , Obésité , Sarcopénie , Mode de vie sédentaire , Humains , Sarcopénie/physiopathologie , Femelle , Mâle , Sujet âgé , Obésité/physiopathologie , Obésité/complications , Exercice physique/physiologie , Sujet âgé de 80 ans ou plus , Muscles squelettiques/physiopathologie , Force de la main , Métabolisme énergétique , Vie autonomeRÉSUMÉ
BACKGROUND & AIMS: Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender. METHODS: The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality. RESULTS: This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1-3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1-1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1-2.4, p = 0.019), while defined by other measurements showed no associations in both sexes. CONCLUSIONS: The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults.
Sujet(s)
Adiposité , Indice de masse corporelle , Obésité , Sarcopénie , Humains , Mâle , Femelle , Sarcopénie/mortalité , Sarcopénie/complications , Études longitudinales , Sujet âgé , Adulte d'âge moyen , Obésité/complications , Obésité/mortalité , Obésité/physiopathologie , Tour de taille , Absorptiométrie photonique , Vieillissement/physiologie , Composition corporelle , Facteurs de risqueRÉSUMÉ
Obesity is associated with an increased risk of incident heart failure with preserved ejection fraction (HFpEF) and, among patients with existing heart failure, is associated with worse quality of life, higher symptom burden, and more HF hospitalizations. Anti-obesity medication (AOM) semaglutide has been shown to be efficacious at both causing intentional weight loss and improving HF symptom burden, with some evidence to suggest that HF clinical events may also be reduced. Additional ongoing trials of AOM in patients with cardiovascular disease, including HFpEF, will further improve insight into the potential role of managing obesity to improve HF status among patients with HFpEF and obesity.