RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is an ancient formula of traditional Chinese medicine that is commonly utilized in a range of disorders, and it has been shown to have pharmacological effects on glucose and lipid metabolism. However, the specific mechanism of HLJDD for the treatment of obesity and related metabolic disorders remains to be further investigated. AIM OF THE STUDY: It has been thought that encouraging adipose thermogenesis to raise the body's energy expenditure is a useful tactic for improving metabolic abnormalities and losing weight. In this study, we investigated the ability and underlying mechanisms of HLJDD to regulate fat cell thermogenesis to improve energy expenditure in obesity. METHODS: The obese mouse model was established on a high-fat diet for 12 weeks. All mice were divided into NC, HFD, HFD with HLJDD of a low dose (2.25 g/kg/d), and HFD with HLJDD of a high dose (4.5 g/kg/d) groups and kept for 4 weeks. In vitro experiments were conducted to evaluate the effects of 5% and 10% HLJDD-containing serum on differentiated 3T3-L1 cells and HDAC3-knocking-down 3T3-L1 cells. RESULTS: The results showed that HLJDD treatment significantly improved glucose and insulin tolerance and decreased the adipocyte radius of WATs, as well as increased energy consumption in obese mice. Besides, HLJDD treatment dramatically increased the levels of thermogenic genes UCP-1 and PGC-1α while suppressing HDAC3 levels in WATs and 3T3-L1 adipocytes. Importantly, the effects of HLJDD on PGC-1α and UCP-1 were blocked in HDAC3 knockdown adipocytes. CONCLUSIONS: Therefore, these results suggest that HLJDD enhanced adipose thermogenesis and improved energy expenditure by inhibiting HDAC3, thereby increasing UCP-1 and PGC-1α expression. These findings amplified the mechanisms of HLJDD and its potential to treat obesity and related metabolic disorders.
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Células 3T3-L1 , Dieta Alta en Grasa , Medicamentos Herbarios Chinos , Histona Desacetilasas , Obesidad , Termogénesis , Animales , Masculino , Ratones , Medicamentos Herbarios Chinos/farmacología , Metabolismo Energético/efectos de los fármacos , Histona Desacetilasas/metabolismo , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/tratamiento farmacológico , Termogénesis/efectos de los fármacos , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genéticaRESUMEN
Pescadillo ribosomal biogenesis factor 1 (PES1), a nucleolar protein initially identified in zebrafish, plays an important role in embryonic development and ribosomal biogenesis. Notably, PES1 has been found to be overexpressed in a number of cancer types, where it contributes to tumorigenesis and cancer progression by promoting cell proliferation, suppressing cellular senescence, modulating the tumor microenvironment (TME) and promoting drug resistance in cancer cells. Moreover, recent emerging evidence suggests that PES1 expression is significantly elevated in the livers of Type 2 diabetes mellitus (T2DM) and obese patients, indicating its involvement in the pathogenesis of metabolic diseases through lipid metabolism regulation. In this review, we present the structural characteristics and biological functions of PES1, as well as complexes in which PES1 participates. Furthermore, we comprehensively summarize the multifaceted role of PES1 in various diseases and the latest insights into its underlying molecular mechanisms. Finally, we discuss the potential clinical translational perspectives of targeting PES1, highlighting its promising as a therapeutic intervention and treatment target.
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Neoplasias , Proteínas de Unión al ARN , Humanos , Animales , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Microambiente Tumoral , Metabolismo de los Lípidos , Terapia Molecular Dirigida/métodos , Obesidad/metabolismo , Obesidad/genéticaRESUMEN
This study gives an insight into certain systemic conditions and factors such as nutrition, age, hematological disorders, hypertension, smoking, obesity, and metabolic syndrome that have a notable effect on the periodontium. The review highlights the importance of taking these factors into consideration in periodontal therapy and their impact on the prognosis of periodontal therapies. The other systemic factors are discussed in detail elsewhere in the special issue.
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Hipertensión , Síndrome Metabólico , Obesidad , Enfermedades Periodontales , Humanos , Pronóstico , Enfermedades Periodontales/terapia , Obesidad/complicaciones , Fumar/efectos adversos , Factores de Edad , Factores de Riesgo , Estado NutricionalRESUMEN
Introduction: obstructive sleep apnea syndrome (OSAS) is the most common sleep-related breathing disorder. Knowledge about OSAS incidence trends could be extremely useful in assessing health needs and implementing preventive measures accordingly. This study aimed at the epidemiological and clinical specificities of OSAS and to give an update on its current chronological trends. Methods: we conducted a retrospective study including all cases of OSAS diagnosed over 11 years, from January 1, 2012, to December 31, 2022, at the Sleep Unit of the Neurophysiology Department of the Sahloul University Hospital, Tunisia. Results: overall, 848 new cases of OSAS were diagnosed. The mean annual number of OSAS cases was 74.8/year. The crude incidence rate (CIR) was 12.3/100000 inhabitants/year, it was significantly increasing over the years (rho=0.7; p=0.01). The median age was 56 (IQR= [48-64]) years, it increased significantly during the study period from 54 years (IQR= [43-63]) in 2012 to 58 years (IQR= [50.5-65]) in 2022 (rho=0.7; p=0.015). The median BMI was 35.5 (IQR= [31.3-40.3]) kg/m2. The median BMI of patients diagnosed with OSAS increased significantly from 34.6 kg/m2 to 38.3 kg/m2 (rho=0.75; p=0.008). This equated to an annual increase in median BMI of 0.41 kg/m2. The median AHI showed a significant upward trend for all patients, rising from 26.30 events/h in 2012 to 34.07 events/h in 2022 (rho=0.68; p=0.02). Conclusion: the CIR of OSAS is related to BMI and age. Thus, we assume that it will continue to increase in the coming years with the rise in obesity and the aging of the population.
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Índice de Masa Corporal , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/epidemiología , Túnez/epidemiología , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Incidencia , Anciano , Obesidad/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Obesity, a multifactorial and complex health condition, has emerged as a significant global public health concern. Integrating machine learning techniques into obesity research offers great promise as an interdisciplinary field, particularly in the screening, diagnosis, and analysis of obesity. Nevertheless, the publications on using machine learning methods in obesity research have not been systematically evaluated. Hence, this study aimed to quantitatively examine, visualize, and analyze the publications concerning the use of machine learning methods in obesity research by means of bibliometrics. METHODS: The Web of Science core collection was the primary database source for this study, which collected publications on obesity research using machine learning methods over the last 20 years from January 1, 2004, to December 31, 2023. Only articles and reviews that fit the criteria were selected for bibliometric analysis, and in terms of language, only English was accepted. VOSviewer, CiteSpace, and Excel were the primary software utilized. RESULTS: Between 2004 and 2023, the number of publications on obesity research using machine learning methods increased exponentially. Eventually, 3286 publications that met the eligibility criteria were searched. According to the collaborative network analysis, the United States has the greatest volume of publications, indicating a significant influence on this research. coauthor's analysis showed the authoritative one in this field is Leo Breiman. Scientific Reports is the most widely published journal. The most referenced publication is "R: a language and environment for statistical computing." An analysis of keywords shows that deep learning, support vector machines, predictive models, gut microbiota, energy expenditure, and genome are hot topics in this field. Future research directions may include the relationship between obesity and its consequences, such as diabetic retinopathy, as well as the interaction between obesity and epidemiology, such as COVID-19. CONCLUSION: Utilizing bibliometrics as a research tool and methodology, this study, for the first time, reveals the intrinsic relationship and developmental pattern among obesity research using machine learning methods, which provides academic references for clinicians and researchers in understanding the hotspots and cutting-edge issues as well as the developmental trend in this field to detect patients' obesity problems early and develop personalized treatment plans.
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Bibliometría , Aprendizaje Automático , Obesidad , Humanos , Obesidad/epidemiología , Investigación Biomédica/métodos , Investigación Biomédica/tendenciasRESUMEN
Many factors determine whether and when a class of therapeutic agents will be successfully developed and brought to market, and historians of science, entrepreneurs, drug developers, and clinicians should be interested in accounts of both successes and failures. Successes induce many participants and observers to document them, whereas failed efforts are often lost to history, in part because involved parties are typically unmotivated to document their failures. The GLP-1 class of drugs for diabetes and obesity have emerged over the past decade as clinical and financial blockbusters, perhaps soon becoming the highest single source of revenue for the pharmaceutical industry (Berk 2023). In that context, it is instructive to tell the story of the first commercial effort to develop this class of drugs for metabolic disease, and how, despite remarkable early success, the work was abandoned in 1990. Told by a key participant in the effort, this story documents history that would otherwise be lost and suggests a number of lessons about drug development that remain relevant today.
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Desarrollo de Medicamentos , Péptido 1 Similar al Glucagón , Humanos , Péptido 1 Similar al Glucagón/historia , Desarrollo de Medicamentos/historia , Historia del Siglo XX , Hipoglucemiantes/historia , Hipoglucemiantes/uso terapéutico , Industria Farmacéutica/historia , Obesidad/historia , Obesidad/tratamiento farmacológicoAsunto(s)
Trastorno por Atracón , Diabetes Mellitus Tipo 1 , Péptidos Similares al Glucagón , Obesidad , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Trastorno por Atracón/tratamiento farmacológico , Femenino , Hipoglucemiantes/uso terapéutico , Adulto , Resultado del Tratamiento , Masculino , Persona de Mediana EdadRESUMEN
Inflammation involving adipose macrophages is an important inducer of obesity. Regulating macrophages polarization and improving the inflammatory microenvironment of adipose tissue is a new strategy for the treatment of obesity. An amphiphilic chondroitin sulfate phenylborate derivative (CS-PBE) was obtained by modifying the main chain of chondroitin sulfate with the hydrophobic small molecule phenylborate. Using CS-PBE self-assembly, macrophage targeting, reactive oxygen species (ROS) release and celastrol (CLT) encapsulation were achieved. The cytotoxicity, cellular uptake, internalization pathways and transmembrane transport efficiency of CS-PBE micelles were studied in Caco-2 and RAW264.7 cells. Hemolysis and organotoxicity tests were performed to assess the safety of the platform, while its therapeutic efficacy was investigated in high-fat diet-induced obese mice. Multifunctional micelles with macrophage targeting and ROS clearance capabilities were developed to improve the efficacy of CLT in treating obesity.In vitrostudies indicated that CS-PBE micelles had better ability to target M1 macrophages, better protective effects on mitochondrial function, better ability to reduce the number of LPS-stimulated M1 macrophages, better ability to reduce the number of M2 macrophages, and better ability to scavenge ROS in inflammatory macrophages.In vivostudies have shown that CS-PBE micelles improve inflammation and significantly reduce toxicity of CLT in the treatment of obesity. In summary, CS-PBE micelles could significantly improve the ability to target inflammatory macrophages and scavenge ROS in adipose tissue to alleviate inflammation, suggesting that CS-PBE micelles are a highly promising approach for the treatment of obesity.
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Macrófagos , Micelas , Mitocondrias , Obesidad , Especies Reactivas de Oxígeno , Animales , Especies Reactivas de Oxígeno/metabolismo , Ratones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Células RAW 264.7 , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Células CACO-2 , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/química , Ratones Endogámicos C57BL , Masculino , Dieta Alta en Grasa/efectos adversos , Triterpenos/farmacología , Triterpenos/químicaRESUMEN
Improving access to kidney transplants remains a priority for the transplant community. However, many medical, psychosocial, geographic, and socioeconomic barriers exist that prevent or delay transplantation for candidates with certain conditions. There is a lack of consensus regarding how to best approach many of these issues and barriers, leading to heterogeneity in transplant centers' management and acceptance practices for a variety of pretransplant candidate issues. In this review, we address several of the more common contemporary patient medical and psychosocial barriers frequently encountered by transplant programs. The barriers discussed here include kidney transplant candidates with obesity, older age, prior malignancy, cardiovascular disease, history of nonadherence, and cannabis use. Improving understanding of how to best address these specific issues can empower referring providers, transplant programs, and patients to address these issues as necessary to progress toward eventual successful transplantation.
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Accesibilidad a los Servicios de Salud , Trasplante de Riñón , Selección de Paciente , Humanos , Trasplante de Riñón/psicología , Selección de Paciente/ética , Obesidad/psicología , Obesidad/cirugía , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/psicología , Factores de Edad , Enfermedades Cardiovasculares/psicología , Cooperación del Paciente/psicología , Neoplasias/psicologíaRESUMEN
BACKGROUND: Elevated body mass index (BMI) is a known perioperative risk factor for complications such as delayed wound healing and infection. However, there is a gap in understanding how elevated BMI impacts outcomes after posttraumatic lower extremity (LE) microvascular reconstruction. METHODS: A retrospective review was performed at a level 1 trauma center between 2007 and 2022 of patients who underwent posttraumatic microvascular LE reconstruction. Demographics, flap/wound details, complications, and outcomes were recorded. Patients were stratified into BMI Center for Disease Control categories. RESULTS: A total of 398 patients were included with an average BMI of 28.2 ± 5.8. Nearly half (45%) of LE defects were located in the distal third of the leg, 27.5% in the middle third, and 34.4% in the proximal third. Most reconstructions utilized muscle-containing flaps (74.4%) compared with fasciocutaneous flaps (16.8%). Surgical approaches included free flaps (47.6%) and local flaps (52.5%). Class III obese patients were significantly more likely to be nonambulatory than nonobese patients (OR: 4.10, 95% CI 1.10-15.2, p = 0.035). At final follow-up, 30.1% of patients with Class III obesity were ambulatory, requiring either wheelchairs (42.3%) or assistance devices (26.9%). There were no significant differences in complication rates based on obesity status (0.704). The average follow-up time for the entire cohort was 5.8 years. CONCLUSIONS: BMI is critical for patient care and surgical decision-making in LE reconstruction. Further research is warranted to optimize outcomes for higher BMI patients, thereby potentially reducing the burden of postoperative complications and enhancing overall patient recovery.
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Índice de Masa Corporal , Traumatismos de la Pierna , Microcirugia , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Humanos , Masculino , Estudios Retrospectivos , Femenino , Adulto , Microcirugia/métodos , Microcirugia/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/efectos adversos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Traumatismos de la Pierna/cirugía , Resultado del Tratamiento , Obesidad/complicaciones , Extremidad Inferior/cirugía , Factores de Riesgo , Colgajos Tisulares Libres/trasplante , Colgajos Tisulares Libres/irrigación sanguínea , Colgajos Tisulares Libres/efectos adversos , Colgajos Quirúrgicos/irrigación sanguínea , Colgajos Quirúrgicos/trasplante , Colgajos Quirúrgicos/efectos adversosRESUMEN
BACKGROUND: Nuciferine (NUC), a natural compound extracted from lotus leaves, has been proven to have anti-obesity effects. However, the development and application of NUC as an anti-obesity drug in dogs are hindered due to its poor water solubility and low bioavailability. OBJECTIVE: To promote the development of NUC-related products for anti-obesity in dogs, this study prepared NUC into a liposome formulation and evaluated its characteristics, pharmacokinetics in dogs, and anti-obesity effects on high-fat diet dogs. METHODS: NUC liposomes were prepared by the ethanol injection method, using NUC, egg lecithin, and ß-sitosterol as raw materials. The characteristics and release rate in vitro of liposomes were evaluated by particle size analyser and dialysis method, respectively. The pharmacokinetics in dogs after oral administration of NUC-liposomes was carried out by the high-performance liquid chromatography (HPLC) method. Moreover, we investigated the anti-obesity effect of NUC-liposomes on obese dogs fed with a high-fat diet. RESULTS: NUC-liposome was successfully prepared, with an EE of (79.31 ± 1.06)%, a particle size of (81.25 ± 3.14) nm, a zeta potential of (-18.75 ± 0.23) mV, and a PDI of 0.175 ± 0.031. The cumulative release rate in vitro of NUC from NUC-liposomes was slower than that of NUC. The T1/2 and relative bioavailability of NUC-liposomes in dogs increased, and CL reduced compared with NUC. In addition, the preventive effect of NUC-liposomes on obesity in high-fat diet dogs is stronger than that of NUC. CONCLUSIONS: The liposome formulation of NUC was conducive to improve its relative bioavailability and anti-obesity effect in dogs.
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Fármacos Antiobesidad , Aporfinas , Liposomas , Obesidad , Animales , Perros , Fármacos Antiobesidad/farmacocinética , Fármacos Antiobesidad/administración & dosificación , Fármacos Antiobesidad/química , Obesidad/veterinaria , Obesidad/tratamiento farmacológico , Masculino , Aporfinas/farmacocinética , Aporfinas/química , Aporfinas/administración & dosificación , Dieta Alta en Grasa , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/prevención & control , FemeninoRESUMEN
BACKGROUND: Obesity, characterized by excessive fat accumulation, poses a significant public health challenge globally. Recent advancements in medical technology have heralded the emergence of endoscopic bariatric treatments (EBTs) as innovative alternatives to conventional obesity interventions. Despite previous systematic reviews and network meta-analyses, they also highlighted discrepancies in outcomes and efficacy among different EBTs. Here, we will update a systematic review and network meta-analysis of randomized controlled trials (RCTs) focusing on EBTs and presents a protocol for the reproducibility and transparency. METHODS: The core protocol of this study was registered at PROSPERO database (CRD42024514249) on Jan 2024. Core databases including MEDLINE through PubMed, Embase, and Cochrane library will be searched relevant studies, and a systematic review with network meta-analysis will be performed. Two evaluators (EJ Gong and CS Bang) will independently screen the titles and abstracts following the eligibility criteria; (1) RCTs investigated the compared the efficacy of EBTs and controls; (2) studies published in English; and (3) studies in full-text format. We will exclude studies meeting the following criteria; (1) studies that did not report the treatment outcomes, such as percent excess weight loss or percent total body weight loss; (2) case reports and review articles; (3) ineligible research objects, for example, animals or children; and (4) insufficient data regarding treatment outcome. The primary outcomes will be the common efficacy metric found after systematic review of relevant studies, such as percent excess weight loss or percent total body weight loss with a follow-up of at least 6 months. Narrative (descriptive) synthesis is planned and quantitative synthesis will be used if the included studies are sufficiently homogenous. The quality of the identified studies will be assessed using the Cochrane Risk of Bias assessment tool version 2.0 (ROB 2.0). All the systematic review and network meta-analysis process will be undertaken keeping the principles of the Preferred Reporting Items for a Systematic Review and Meta-analysis for systematic review protocols (PRISMA-P) and PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA). DISCUSSION: This updated systematic review and network meta-analysis will provide information about comparative efficacy of various EBTs and this will help physicians in the decision-making process for the selection of treatment modalities in the clinical practice.
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Metaanálisis en Red , Obesidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Humanos , Obesidad/cirugía , Cirugía Bariátrica/métodos , Endoscopía/métodos , Metaanálisis como Asunto , Pérdida de Peso , Resultado del TratamientoRESUMEN
Weight-adjusted-waist index (WWI) is an emerging parameter for evaluating obesity. We sought to ascertain the link between WWI and circadian syndrome (CircS). The study population consisted of 8275 eligible subjects who were included in the ultimate analysis from the NHANES 2011-2018. By using multivariable regression models, the association of WWI and CircS was analyzed. In subgroup analysis, we explored the relationship in different groups and tested the stability of the intergroup connection using interaction testing. To investigate whether WWI and CircS had a potential non-linear relationship, smooth curve fittings, and threshold effects tests were also constructed. In a multivariate linear regression model, WWI is significantly positively related to CircS (OR = 1.77, 95% CI 1.50-2.08). Through subgroup analysis and interaction testing, the stability of this positive association was also validated. It was further found that there was an inverted U-shaped association, with a turning point of 11.84, between WWI and CircS. Our findings supported a strong association between WWI values and CircS. Central obesity management is pivotal for preventing or alleviating CircS.
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Circunferencia de la Cintura , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Peso Corporal , Obesidad/epidemiología , Trastornos Cronobiológicos/fisiopatología , Índice de Masa Corporal , Anciano , Encuestas NutricionalesRESUMEN
BACKGROUND: Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established. METHODS: We conducted a post-hoc pooled, participant-level analysis of four randomised, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) to examine the effects of once-weekly subcutaneous semaglutide (2·4 mg in SELECT, STEP-HFpEF, and STEP-HFpEF DM; 1·0 mg in FLOW) on heart failure events. The STEP-HFpEF and STEP-HFpF DM trials enrolled participants with obesity-related HFpEF, the SELECT trial enrolled participants with atherosclerotic cardiovascular disease and overweight or obesity, and the FLOW trial enrolled participants with type 2 diabetes and chronic kidney disease. Hence, for this analysis, we include all participants from the STEP-HFpEF trials and those with an investigator-reported history of HFpEF from SELECT and FLOW. The main outcomes for this analysis were the composite endpoint of time to cardiovascular death or first worsening heart failure event (defined as hospitalisation or urgent visit due to heart failure), time to first worsening heart failure event, and time to cardiovascular death. Efficacy and safety endpoints were analysed with the full analysis set (ie, all participants randomly assigned to treatment, according to the intention-to-treat principle). The SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials are registered at ClinicalTrials.gov, NCT03574597, NCT03819153, NCT04788511, and NCT04916470, respectively, and all are complete. FINDINGS: Across the four trials, 3743 (16·8%) of 22 282 participants had a history of HFpEF (1914 assigned to semaglutide and 1829 assigned to placebo). In this group of participants with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or heart failure events (103 [5·4%] of 1914 in the semaglutide group had events vs 138 [7·5%] of 1829 in the placebo group; hazard ratio [HR] 0·69 [95% CI 0·53-0·89]; p=0·0045). Semaglutide also reduced the risk of worsening heart failure events (54 [2·8%] vs 86 [4·7%]; HR 0·59 [0·41-0·82]; p=0·0019). No significant effect on cardiovascular death alone was seen (59 [3·1%] vs 67 [3·7%]; HR 0·82 [0·57-1·16]; p=0·25). A lower proportion of patients treated with semaglutide had serious adverse events than did those who were treated with placebo (572 [29·9%] vs 708 [38·7%]). INTERPRETATION: In patients with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or worsening heart failure events, and worsening heart failure events alone, whereas its effect on cardiovascular death alone was not significant. These data support the use of semaglutide as an efficacious therapy to reduce the risk of clinical heart failure events in patients with HFpEF, for whom few treatment options are currently available. FUNDING: Novo Nordisk.
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Agonistas Receptor de Péptidos Similares al Glucagón , Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Volumen Sistólico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Péptidos Similares al Glucagón/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Obesidad/tratamiento farmacológico , Resultado del Tratamiento , Agonistas Receptor de Péptidos Similares al Glucagón/uso terapéuticoRESUMEN
BACKGROUND: China has undergone a significant socioeconomic transformation over the past few decades due to the implementation of family planning policies. These societal changes have resulted in an increased susceptibility among females to developing cardiometabolic diseases (CMD). Unfortunately, studies investigating the correlation between family planning policies in China and the incidence of CMD remain scarce. METHODS: Data from 1,226 females, aged 30 years or older with ≥ 1 live birth, undergoing routine physical examinations between January 2018 and December 2021 were collected, and they were grouped by number of live births 1, 2, and ≥ 3. A binary logistic regression model was employed to examine the association between the number of live births with CMD. Furthermore, the subgroup analysis was performed to elucidate the impact of the implementation of family planning policies with CMD. RESULTS: Women with live births ≥ 3 tended to be older, had higher gravidities, a greater proportion of central obesity, general obesity, hypertension, and dyslipidemia (all P < 0.05). Across the three groups (live birth = 1, =2 and ≥ 3), the odds ratio (OR) with 95% CI for obesity were: 1.00, 3.32 (2.36-4.69), and 5.73 (3.79-8.68); for dyslipidemia were: 1.00, 1.75 (1.29-2.39), and 2.02 (1.38-2.94); and for CMD were: 1.00, 1.91 (1.44-2.54), and 2.15 (1.46-3.15), respectively (all P < 0.05). In addition, based on the different periods of the childbearing policy in China, a subgroup analysis (where age was divided into ≤ 45, 45-65, and ≥ 65 years old) found that each additional live birth increased the prevalence risk of obesity and CMD in the younger generations, while hypertension and dyslipidemia in the elder generation. CONCLUSIONS: Higher live births are positively associated with the prevalence of CMD among women in Southwest China. Moreover, giving birth after the implementation of the one-child policy tends to have a higher risk of developing CMD.
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Nacimiento Vivo , Humanos , Femenino , China/epidemiología , Adulto , Nacimiento Vivo/epidemiología , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Embarazo , Factores de Riesgo , Obesidad/epidemiología , Enfermedades Metabólicas/epidemiología , Política de Planificación Familiar , Dislipidemias/epidemiología , Incidencia , Pronóstico , Pueblos del Este de AsiaRESUMEN
Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1 and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.
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Modelos Animales de Enfermedad , Hipoglucemiantes , Síndrome Metabólico , Obesidad , Animales , Perros , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Masculino , Glucemia/metabolismo , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Péptido Natriurético Encefálico/sangre , Péptido Natriurético Encefálico/metabolismo , Estrés Oxidativo/efectos de los fármacos , FemeninoRESUMEN
INTRODUCTION: Asymmetric dimethylarginine (ADMA), a cardiovascular risk factor, increases in renal failure. The aim of this study was to investigate ADMA levels in normal weight and obese patients on hemodialysis. METHODS: In this cross-sectional study, 43 normal weight and 43 obese patients on regular hemodialysis were examined. Malnutrition-inflammation score (MIS), anthropometry, circulating ADMA, lipid profiles including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipid ratios, glucose homeostasis parameters, blood pressure, and high-sensitivity C-reactive protein (hs-CRP) were assessed. RESULTS: Serum levels of ADMA were significantly lower in the obese compared to the normal weight patients (10268.2 ± 10092.4 vs. 13765.2 ± 9951.3 ng/l, P = 0.03). At the same time MIS score (6.1 ± 2.4 vs. 10.7 ± 3.2, P < 0.001), systolic blood pressure (119 ± 26.8 vs. 134.2 ± 24.7 mmHg, P = 0.018) and mean arterial pressure (91.3 ± 18.6 vs. 100.9 ± 15.9 mmHg, P = 0.028) were significantly lower in the obese than the normal weight group. Fasting blood glucose (P = 0.045), TG/HDL (P = 0.03), TC/HDL (P = 0.019), and LDL/HDL (P = 0.005) ratios, and hs-CRP (P = 0.015) levels were significantly higher in the obese than in the normal weight group. CONCLUSION: Circulating ADMA was significantly lower in obese than in normal weight patients on hemodialysis, which was concomitant with lower MIS, indicating a better nutritional inflammatory status, and lower blood pressure.
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Arginina , Obesidad , Diálisis Renal , Humanos , Arginina/análogos & derivados , Arginina/sangre , Masculino , Femenino , Obesidad/sangre , Obesidad/complicaciones , Persona de Mediana Edad , Estudios Transversales , Adulto , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Biomarcadores/sangre , AncianoRESUMEN
Metabolic dysfunction-associated diseases often refer to various diseases caused by metabolic problems such as glucose and lipid metabolism disorders. With the improvement of living standards, the increasing prevalence of metabolic diseases has become a severe public health problem, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), diabetes and obesity. These diseases are both independent and interdependent, with complex and diverse molecular mechanisms. Therefore, it is urgent to explore the molecular mechanisms and find effective therapeutic targets of these diseases. MicroRNAs (miRNAs) have emerged as key regulators of metabolic homoeostasis due to their multitargets and network regulatory properties within the past few decades. In this review, we discussed the latest progress in the roles of miRNA-mediated regulatory networks in the development and progression of MASLD, ALD, diabetes and obesity.
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Enfermedades Metabólicas , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Animales , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/terapia , Enfermedades Metabólicas/genética , Obesidad/metabolismo , Obesidad/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Hígado Graso/metabolismo , Hígado Graso/genética , Hígado Graso/terapia , Hígado Graso/etiologíaRESUMEN
BACKGROUND: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex. METHODS: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models. RESULTS: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape. CONCLUSIONS: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.