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BACKGROUND: Obesity-associated dysfunctional intestinal permeability contributes to systemic chronic inflammation leading to the development of metabolic diseases. The inflammasomes constitute essential components in the regulation of intestinal homeostasis. We aimed to determine the impact of the inflammasomes in the regulation of gut barrier dysfunction and metabolic inflammation in the context of obesity and type 2 diabetes (T2D). METHODS: Blood samples obtained from 80 volunteers (n = 20 normal weight, n = 21 OB without T2D, n = 39 OB with T2D) and a subgroup of jejunum samples were used in a case-control study. Circulating levels of intestinal damage markers and expression levels of inflammasomes as well as their main effectors (IL-1ß and IL-18) and key inflammation-related genes were analyzed. The impact of inflammation-related factors, different metabolites and Akkermansia muciniphila in the regulation of inflammasomes and intestinal integrity genes was evaluated. The effect of blocking NLRP6 by using siRNA in inflammation was also studied. RESULTS: Increased circulating levels (P < 0.01) of the intestinal damage markers endotoxin, LBP, and zonulin in patients with obesity decreased (P < 0.05) after weight loss. Patients with obesity and T2D exhibited decreased (P < 0.05) jejunum gene expression levels of NLRP6 and its main effector IL18 together with increased (P < 0.05) mRNA levels of inflammatory markers. We further showed that while NLRP6 was primarily localized in goblet cells, NLRP3 was localized in the intestinal epithelial cells. Additionally, decreased (P < 0.05) mRNA levels of Nlrp1, Nlrp3 and Nlrp6 in the small intestinal tract obtained from rats with diet-induced obesity were found. NLRP6 expression was regulated by taurine, parthenolide and A. muciniphila in the human enterocyte cell line CCL-241. Finally, a significant decrease (P < 0.01) in the expression and release of MUC2 after the knockdown of NLRP6 was observed. CONCLUSIONS: The increased levels of intestinal damage markers together with the downregulation of NLRP6 and IL18 in the jejunum in obesity-associated T2D suggest a defective inflammasome sensing, driving to an impaired epithelial intestinal barrier that may regulate the progression of multiple obesity-associated comorbidities.
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Diabetes Mellitus Tipo 2 , Inflamassomos , Humanos , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Função da Barreira Intestinal , Estudos de Casos e Controles , Inflamação , Obesidade/complicações , RNA Mensageiro/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Receptores de Angiotensina/metabolismo , Receptores de Vasopressinas/metabolismoRESUMO
BACKGROUND: Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status. METHODS: A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome. RESULTS: After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20-8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69-22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15-30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]). CONCLUSIONS: Identification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction.
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Adiposidade , Albuminúria , Fígado Gorduroso , Pericárdio , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pericárdio/diagnóstico por imagem , Albuminúria/epidemiologia , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/fisiopatologia , Estudos Longitudinais , Fatores de Tempo , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/fisiopatologia , Tecido Adiposo/metabolismo , Medição de Risco , Fígado/diagnóstico por imagem , Fígado/patologia , Gordura Intra-Abdominal/fisiopatologia , Gordura Intra-Abdominal/diagnóstico por imagem , AdultoRESUMO
The majority of cases of chronic kidney disease (CKD) worldwide are driven by the presence of type 2 diabetes (T2D), resulting in an increase in CKD rates over the past few decades. The existence of CKD alongside diabetes is associated with increased burden of cardiovascular disease and increased risk of death. Optimal glycaemic control is essential to prevent progression of CKD, but achieving glycaemic targets in people with CKD and diabetes can be challenging because of increased risk of hypoglycaemia and limitations on glucose-lowering therapeutic options. This review considers the challenges in management of T2D in people with impaired kidney function and assesses evidence for use of basal insulin analogues in people with CKD.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemia/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamenteRESUMO
Obesity is considered a chronic disease and a serious public-health issue in Spain, as well as in many other countries, primarily because of it being a significant risk factor for multiple chronic conditions, including diabetes mellitus type 2, cardiovascular disease, respiratory disease, metabolic dysfunction-associated fatty liver disease, gastrointestinal conditions (gastroesophageal reflux, diverticulosis), musculoskeletal difficulties, infertility, and even development of some malignancies such as postmenopausal breast cancer, and colorectal, endometrial, renal, esophageal, pancreatic, hepatic, and gallbladder neoplasms. Furthermore, weight loss, whether as therapy goal or voluntary, has been shown to be beneficial for virtually all these health conditions, the more so the greater weight loss.
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Fármacos Antiobesidade , Obesidade , Adulto , Humanos , Fármacos Antiobesidade/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Redução de PesoRESUMO
OBJECTIVE: To assess how inaccurately the body mass index (BMI) is used to diagnose obesity compared to body fat percentage (BF%) measurement and to compare the cardiometabolic risk in children and adolescents with or without obesity according to BMI but with a similar BF%. METHODS: A retrospective cross-sectional investigation was conducted including 553 (378 females/175 males) white children and adolescents aged 6-17 years, 197 with normal weight (NW), 144 with overweight (OW) and 212 with obesity (OB) according to BMI. In addition to BMI, BF% measured by air displacement plethysmography, as well as markers of cardiometabolic risk had been determined in the existing cohort. RESULTS: We found that 7% of subjects considered as NW and 62% of children and adolescents classified as OW according to BMI presented a BF% within the obesity range. Children and adolescents without obesity by the BMI criterion but with obesity by BF% exhibited higher blood pressure and C-reactive protein (CRP) in boys, and higher blood pressure, glucose, uric acid, CRP and white blood cells count, as well as reduced HDL-cholesterol, in girls, similar to those with obesity by BMI and BF%. Importantly, both groups of subjects with obesity by BF% showed a similarly altered glucose homeostasis after an OGTT as compared to their NW counterparts. CONCLUSIONS: Results from the present study suggest increased cardiometabolic risk factors in children and adolescents without obesity according to BMI but with obesity based on BF%. Being aware of the difficulty in determining body composition in everyday clinical practice, our data show that its inclusion could yield clinically useful information both for the diagnosis and treatment of overweight and obesity.
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Adiposidade , Hipertensão , Masculino , Feminino , Humanos , Adolescente , Criança , Índice de Massa Corporal , Sobrepeso , Estudos Transversais , Estudos Retrospectivos , Obesidade/diagnóstico , Obesidade/epidemiologia , Proteína C-Reativa , GlucoseRESUMO
Academic medicine fosters research that moves from discovery to translation, at the same time as promoting education of the next generation of professionals. In the field of obesity, the supposed integration of knowledge, discovery and translation research to clinical care is being particularly hampered. The classification of obesity based on the body mass index does not account for several subtypes of obesity. The lack of a universally shared definition of "obesities" makes it impossible to establish the real burden of the different obesity phenotypes. The individual's genotype, adipotype, enterotype and microbiota interplays with macronutrient intake, appetite, metabolism and thermogenesis. Further investigations based on the concept of differently diagnosed "obesities" are required.
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Obesidade , Índice de Massa Corporal , Humanos , Obesidade/metabolismoRESUMO
Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-α and TGF-ß), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC.
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Neoplasias do Colo , Proteínas da Matriz Extracelular , Células CACO-2 , Estudos de Casos e Controles , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Inflamação/metabolismo , Obesidade/complicações , Obesidade/metabolismo , RNA Mensageiro/metabolismoRESUMO
PURPOSE: To evaluate labeling efficiency of pseudo-continuous arterial spin labeling (PCASL) and to find the gradient parameters that increase PCASL robustness for renal perfusion measurements. METHODS: Aortic blood flow was characterized in 3 groups: young healthy volunteers (YHV1), chronic kidney disease (CKD) patients (CKDP), and healthy controls (HCO). PCASL inversion efficiency was evaluated through numeric simulations considering the measured pulsatile flow velocity profiles and off-resonance effects for a wide range of gradient parameters, and the results were assessed in vivo. The most robust PCASL implementation was used to measure renal blood flow (RBF) in CKDP and HCO. RESULTS: Aortic blood velocities reached peak values of 120 cm/s in YHV1, whereas for elderly subjects values were lower by approximately a factor of 2. Simulations and experiments showed that by reducing the gradient average (Gave ) and the selective to average gradient ratio (Gmax /Gave ), labeling efficiency was maximized and PCASL robustness to off-resonance was improved. The study in CKDP and HCO showed significant differences in RBF between groups. CONCLUSION: An efficient and robust PCASL scheme for renal applications requires a Gmax /Gave ratio of 6-7 and a Gave value that depends on the aortic blood flow velocities (0.5 mT/m being appropriate for CKDP and HCO).
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Interpretação de Imagem Assistida por Computador , Angiografia por Ressonância Magnética , Idoso , Velocidade do Fluxo Sanguíneo , Encéfalo , Circulação Cerebrovascular , Humanos , Imageamento por Ressonância Magnética , Perfusão , Imagem de Perfusão , Reprodutibilidade dos Testes , Marcadores de SpinRESUMO
Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.
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Proteína 8 Semelhante a Angiopoietina/metabolismo , Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Hormônios Peptídicos/metabolismo , Adulto , Proteína 8 Semelhante a Angiopoietina/sangue , Proteína 8 Semelhante a Angiopoietina/genética , Animais , Modelos Animais de Doenças , Feminino , Gastrectomia , Derivação Gástrica , Hepatócitos/metabolismo , Humanos , Lipogênese , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Mórbida/complicações , Hormônios Peptídicos/sangue , Hormônios Peptídicos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND AND AIMS: Obesity is associated with impaired glucose tolerance which is a risk factor for cardiovascular risk. However, the oral glucose tolerance test (OGTT) is not usually performed in patients with normal fasting glycaemia, thus offering false reassurance to patients with overweight or obesity who may have post-prandial hyperglycaemia. As an alternative to resource demanding OGTTs, we aimed to examine the predictive value of anthropometric measures of total and central fat distribution for post-prandial hyperglycaemia in patients with overweight and obesity with normal fasting glycaemia enrolled in the DICAMANO study. METHODS: We studied 447 subjects with overweight/obesity with a fasting glucose value ≤ 5.5 mmol l-1 (99 mg dl-1) and BMI ≥ 25 kg/m2 who underwent a 75-g OGTT. Post-prandial hyperglycaemia was defined as a glucose level ≥ 7.8 mmol l-1 (140 mg dl-1) 2-h after the OGTT. The anthropometric measurements included body mass index, body adiposity index, waist circumference, neck circumference, waist-to-hip ratio and waist-to-height ratio. RESULTS: The prevalence of post-prandial hyperglycaemia was 26%. Mean 1-h OGTT glucose levels, insulin resistance and beta cell dysfunction was higher in those subjects in the highest tertile for each anthropometric measurement, irrespective of fasting glucose level. Central fat depot anthropometric measurements were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. After multivariable-adjustment for fasting plasma glucose level, smoking, and physical activity level, the odds ratio (95% confidence intervals) for the presence of post-prandial hyperglycaemia for neck circumference, waist circumference and waist-to-height ratio were 3.3 (1.4, 7.7), 2.4 (1.4, 4.4) and 2.5 (1.4, 4.5), respectively. CONCLUSIONS: In this large and comprehensively phenotyped cohort, one in four subjects had post-prandial hyperglycaemia despite normal fasting glycaemia. Anthropometric indices of central fat distribution were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. These results support the association between central adiposity and glucose derangements and demonstrate the clinical usefulness of anthropometric measurements as screening tools for the selection of patients who are most likely to benefit from an OGTT. Trial registration ClinicalTrials.gov Identifier: NCT03506581. Registered 24 April 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03506581.
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Adiposidade , Antropometria , Glicemia/metabolismo , Jejum/sangue , Hiperglicemia/sangue , Período Pós-Prandial , HumanosRESUMO
BACKGROUND: The feasibility of beta cell mass (BCM) imaging and quantification with positron emission tomography (PET) in the pancreas is controversial. In an effort to shed some light on this topic, we have used a xenograft model of rat insulinoma (RIN) in mice, mimicking an intramuscular islet transplantation situation. METHODS: A total of 105 RIN cells were subcutaneously implanted in nude mice (N.=8). Tumor size and glycaemia levels were determined daily. Rat C-peptide was measured to demonstrate rat insulin production. PET imaging with 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) was done at 3 and 4 weeks and compared with 18F-FDG and 18F-DOPA studies in the same mice. Ex-vivo autoradiography with 11C-DTBZ was carried out in frozen sections of tumors. VMAT2 expression was measured by Western-blot and immunohistochemistry in tumors and RIN cells. RESULTS: Functional rat insulin production in mice was demonstrated by substantial decrease in glycaemia (<50 mg/dL by week 4) and rat C-peptide levels (7.2±2.6 ng/mL) similar to those measured in control rats. PET studies showed that tumor imaging with 11C-DTBZ at four (N.=8) and five (N.=5) weeks was negative; only bigger tumors could be seen with 18F-DOPA. In explanted tumors 11C-DTBZ autoradiography was negative, albeit VMAT2 expression measured by Western-blot and immunohistochemistry was lower than in cultured RIN cells. CONCLUSIONS: Although insulinomas are fully functional it does not seem feasible to use 11C-DTBZ for in-vivo measuring of BCM. This might either be due to inherent technical limitations of PET, decrease in VMAT2 expression in the tumors due to unknown reasons, or other biological limiting facts.
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Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/química , Tetrabenazina/análogos & derivados , Animais , Radioisótopos de Carbono , Linhagem Celular Tumoral , Fluordesoxiglucose F18/química , Xenoenxertos , Insulinoma/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Pancreáticas/metabolismo , Ratos , Ratos Wistar , Tetrabenazina/química , Proteínas Vesiculares de Transporte de Monoamina/metabolismoRESUMO
Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations.
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Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Algoritmos , Progressão da Doença , Humanos , Guias de Prática Clínica como Assunto , Insuficiência Renal Crônica/complicaçõesRESUMO
BACKGROUND: The molecular mediators responsible for the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis (MASH) have not yet been completely disentangled. We sought to analyze whether FNDC4, an hepatokine and adipokine with anti-inflammatory properties, is involved in TNF-α-induced inflammatory cell death in patients with MASLD. METHODS: Plasma FNDC4 (n = 168) and hepatic FNDC4 and inflammatory cell death (n = 65) were measured in samples from patients with severe obesity with available liver biopsy-proven MASLD diagnosis. The effect of FNDC4 on TNF-α-induced pyroptosis, apoptosis and necroptosis (PANoptosis) and mitochondrial dysfunction was studied in vitro using human HepG2 hepatocytes. RESULTS: Compared with individuals with normal liver, patients with type 2 diabetes and MASLD exhibited decreased hepatic FNDC4 mRNA and protein levels, which were related to liver inflammation. An overexpression of TNF-α, its receptor TNF-R1 and factors involved in inflammatory cell death was also found in the liver of these patients. FNDC4-knockdown in HepG2 hepatocytes increased apoptotic cell death, while FNDC4 treatment blunted NLRP3 inflammasome-induced pyroptosis, apoptosis and necroptosis in TNF-α-stimulated hepatocytes. Moreover, FNDC4 improved TNF-α-induced hepatocyte mitochondrial dysfunction by enhancing mitochondrial DNA (mtDNA) copy number and OXPHOS complex subunits I, II, III and V protein expression. Mechanistically, AMP-activated protein kinase α (AMPKα) was required for the FNDC4-mediated inhibition of cell death and increase in mtDNA content. CONCLUSIONS: FNDC4 acts as a hepatocyte survival factor favouring mitochondrial homeostasis and decreasing inflammatory cell death via AMPKα. Collectively, our study identifies FNDC4 as an attractive target to prevent hepatocellular damage in patients with MASLD.
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BACKGROUND: The estimation of obesity-associated cardiometabolic risk does not usually take into account body composition or the distribution of adiposity. The aim of the present study was to assess the clinical usefulness of a novel obesity phenotyping system based on the combination of actual body fat percentage (BF%) and waist circumference (WC) according to the cardiometabolic risk estimation. METHODS: A classification matrix combining BF% and WC as measures of both amount and distribution of adiposity establishing nine body phenotypes (3 BF% x 3 WC) was developed. Individuals were grouped in five different cardiometabolic risk phenotypes. We conducted a validation study in a large cohort of White subjects from both genders representing a wide range of ages and adiposity (n = 12,754; 65 % females, aged 18-88 years). RESULTS: The five risk groups using the matrix combination of BF% and WC exhibited a robust linear distribution regarding cardiometabolic risk, estimated by the Metabolic Syndrome Severity Score, showing a continuous increase between groups with significant differences (P < 0.001) among them, as well as in other cardiometabolic risk factors. An additional 24 % of patients at very high risk was detected with the new classification system proposed (P < 0.001) as compared to an equivalent matrix using BMI and WC instead of BF% and WC. CONCLUSIONS: A more detailed phenotyping should be a priority in the diagnosis and management of patients with obesity. Our classification system allows to gradually estimate the cardiometabolic risk according to BF% and WC, thus representing a novel and useful tool for both research and clinical practice.
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Adiposidade , Fatores de Risco Cardiometabólico , Síndrome Metabólica , Obesidade , Fenótipo , Circunferência da Cintura , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Adulto , Idoso de 80 Anos ou mais , Adolescente , Adulto Jovem , Síndrome Metabólica/diagnóstico , Medição de Risco/métodos , Índice de Massa Corporal , Doenças Cardiovasculares/etiologiaRESUMO
Early and intensive treatment of type 2 diabetes (T2D) has been associated with lower risk of diabetes-related complications. Control of overweight and obesity, which are strongly associated with T2D and many of its complications, is also key in the management of the disease. New therapies allow for individualised glycaemic control targets with greater safety. Thus, in patients with a higher cardiovascular and renal risk profile, current guidelines encourage early treatment with metformin together with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit. GLP-1 RAs combine highly efficacious glucose-lowering activity with a reduced risk of hypoglycaemia. Recently, tirzepatide, a first-in-class drug that activates both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, has demonstrated very high efficacy in glycated haemoglobin (HbA1c) and weight reduction in clinical trials. Tirzepatide has the potential to help people with T2D reach recommended glycaemic and weight targets (HbA1c < 7% and > 5% weight reduction) and to allow some patients to reach HbA1c measurements close to normal physiological levels and substantial weight reduction. In 2022, tirzepatide was approved by the US Food and Drug Administration and the European Medicines Agency for treatment of people with T2D and is currently in development for chronic weight management.
In people newly diagnosed with type 2 diabetes, early and intensive treatment of the disease can help control blood sugar and reduce the risk of later complications. The need to control weight in people with obesity and diabetes has also recently become a priority. New drugs developed in recent years allow for better and more individualised management of blood sugar without the risk of blood sugar levels dropping too low. In patients at risk of kidney or heart disease, the current recommendation is early treatment with metformin and drugs with proven cardiovascular benefit. Tirzepatide is a new drug that has also demonstrated very high efficacy in reducing blood glucose and body weight. It has the potential to help people with type 2 diabetes achieve their goals and prevent other diabetes-related complications. It is likely that some patients will even be able to bring their blood glucose to normal levels and lose substantial amounts of weight. The US and European regulatory agencies approved tirzepatide in 2022 for the treatment of type 2 diabetes and it is currently being tested for chronic weight management.
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Unhealthy dietary habits and sedentarism coexist with a rising incidence of excess weight and associated comorbidities. We aimed to analyze the dietary and drinking patterns of patients with excess weight, their main characteristics, plausible gender differences and impact on cardiometabolic risk factors, with a particular focus on the potential contribution of beer consumption. Data from 200 consecutive volunteers (38 ± 12 years; 72% females) living with overweight or class I obesity attending the obesity unit to lose weight were studied. Food frequency questionnaires and 24 h recalls were used. Reduced-rank regression (RRR) analysis was applied to identify dietary patterns (DPs). Anthropometry, total and visceral fat, indirect calorimetry, physical activity level, comorbidities and circulating cardiometabolic risk factors were assessed. Study participants showed high waist circumference, adiposity, insulin resistance, dyslipidemia, pro-inflammatory adipokines and low anti-inflammatory factors like adiponectin and interleukin-4. A low-fiber, high-fat, energy-dense DP was observed. BMI showed a statistically significant (p < 0.05) correlation with energy density (r = 0.80) as well as percentage of energy derived from fat (r = 0.61). Excess weight was associated with a DP low in vegetables, legumes and whole grains at the same time as being high in sweets, sugar-sweetened beverages, fat spreads, and processed meats. RRR analysis identified a DP characterized by high energy density and saturated fat exhibiting negative loadings (>-0.30) for green leafy vegetables, legumes, and fruits at the same time as showing positive factor loadings (>0.30) for processed foods, fat spreads, sugar-sweetened beverages, and sweets. Interestingly, for both women and men, wine represented globally the main source of total alcohol intake (p < 0.05) as compared to beer and distillates. Beer consumption cannot be blamed as the main culprit of excess weight. Capturing the DP provides more clinically relevant and useful information. The focus on consumption of single nutrients does not resemble real-world intake behaviors.
Assuntos
Fatores de Risco Cardiometabólico , Dieta , Masculino , Humanos , Feminino , Dieta/efeitos adversos , Obesidade/epidemiologia , Obesidade/etiologia , Comportamento Alimentar , Aumento de Peso , Verduras , Dieta com Restrição de Gorduras , Consumo de Bebidas Alcoólicas/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVES: RECALSEEN project aims to analyze the structure, activity, and outcomes of the departments of endocrinology and nutrition (S-U_EyN) of the Spanish National Health System (SNHS). Based on the results obtained, the challenges for the specialty are analyzed and proposals for improvement policies are made. In this paper 2021 survey data and activity data from the 2007-2019 from the Minimum Basic Data Set (MBDS) are presented. MATERIAL AND METHODS: Cross-sectional descriptive study of the S-U_EyN of acute general hospitals of the NHS in 2020. Data were obtained through: 1. an "ad hoc" survey answered by the S-U_EyN' consultants; and 2. analysing the acute general hospital discharges from S-U_EyN and discharges with endocrine-metabolic comorbidities registered in the minimum basis data set (MBDS) of the SNHS. RESULTS: 112 responses from S-U_EyN were obtained from a total of 154 general acute hospitals of the NHS (73%). The 2021 S-U_EyN sample includes 24 more centers than in 2017. 54% of the S-U_EyN were endocrinology departments. The median number of endocrinologists per S-U_EyN was 7. The estimated rate of endocrinologists was 2.5 per 100,000 inhabitants. S-U_EyN showed a high level of collaboration with primary care teams and other hospital units. Use of telemedicine by S-U_EyN experienced a high increase in 2020. Notable differences in resources and activity have been found between hospitals and Autonomous Communities. There was a wide margin for improvement in quality management. CONCLUSIONS: RECALSEEN is a useful project for the analysis of S-U_EyN. The remarkable variability found in the indicators of structure, activity and management probably indicates a wide margin for improvement.
Assuntos
Endocrinologia , Humanos , Espanha , Estudos Transversais , Hospitais Gerais , Unidades HospitalaresRESUMO
BACKGROUND: Growing evidence suggests the key role of ghrelin in the onset and progression of nonalcoholic fatty liver disease (NAFLD). The potential participation of ghrelin and the ghrelin receptor antagonist, LEAP-2, in the onset of liver fibrosis in patients with severe obesity and NAFLD through the regulation of TGF-ß1-induced hepatic stellate cell (HSC) activation was investigated. METHODS: Circulating (n = 179) and hepatic expression (n = 95) of ghrelin and LEAP-2 were measured in patients with severe obesity and available liver pathology analysis undergoing Roux-en-Y gastric bypass (RYGB). The effect of ghrelin isoforms and LEAP-2 on TGF-ß1-induced HSC activation, fibrogenic response, and contractile properties was evaluated in vitro in human LX-2 cells. RESULTS: Plasma and hepatic ghrelin were negatively associated, while LEAP-2 exhibited a positive association with liver fibrosis in patients with obesity and NAFLD. Six months after RYGB, hepatic function was improved and, although acylated ghrelin and LEAP-2 concentrations remained unchanged, both hormones were inversely related to post-surgical levels of profibrogenic factors TGF-ß1 and TIMP-1. Acylated ghrelin treatment reversed TGF-ß1-induced myofibroblast-like phenotype, collagen contractile properties, and the upregulation of factors involved in HSC activation and fibrogenesis via PI3K/Akt/mTOR pathway. Moreover, acylated ghrelin inhibited the mild HSC activation induced by LEAP-2. CONCLUSIONS: Ghrelin is an anti-fibrogenic factor blocking HSC activation induced by the most potent fibrogenic cytokine, TGF-ß1, and LEAP-2. The imbalance between acylated ghrelin and ghrelin receptor antagonist LEAP-2 might contribute to maintain liver fibrosis in patients with obesity and NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator de Crescimento Transformador beta1/efeitos adversos , Fator de Crescimento Transformador beta1/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Grelina/efeitos adversos , Receptores de Grelina , Cirrose Hepática/etiologia , Fígado/metabolismoRESUMO
BACKGROUND: The biological mediators supporting the resolution of liver steatosis, inflammation and fibrosis after bariatric surgery in patients with obesity and NAFLD remain unclear. We sought to analyze whether uroguanylin and guanylin, two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of obesity-associated NAFLD after bariatric surgery. METHODS: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis. Pathways involved in lipid metabolism, mitochondrial network and fibrogenesis were evaluated in liver biopsies (n = 137). The effect of guanylin and uroguanylin on these metabolic functions was assessed in HepG2 hepatocytes and LX-2 hepatic stellate cells (HSC) under lipotoxic and profibrogenic conditions. RESULTS: Plasma and hepatic expression of GUCA2B were decreased in obesity-associated NAFLD. Both GUCA2A and GUCA2B levels were increased after sleeve gastrectomy and Roux-en-Y gastric bypass in parallel to the improved liver function. The liver of patients with type 2 diabetes showed impaired mitochondrial ß-oxidation, biogenesis, dynamics as well as increased fibrosis. Uroguanylin diminished the lipotoxicity in palmitate-treated HepG2 hepatocytes, evidenced by decresased steatosis and lipogenic factors, as well as increased mitochondrial network expression, AMPK-induced ß-oxidation and oxygen consumption rate. Additionally, uroguanylin, but not guanylin, reversed HSC myofibroblast transdifferentiation as well as fibrogenesis after TGF-ß1 stimulation. CONCLUSIONS: Uroguanylin constitutes a protective factor against lipotoxicity, mitochondrial dysfunction and fibrosis. Increased GUCA2B levels might contribute to improve liver injury in patients with obesity-associated NAFLD after bariatric surgery.