Background: Heart failure with preserved ejection fraction (HFpEF) is a high prevalence condition, with high rates of hospitalization and mortality. Arterial hypertension is the main risk factor for HFpEF. Among hypertensive patients, alterations in cardiac and vascular morphology identify hypertension-mediated organ damage (HMOD).
View Article and Find Full Text PDFBackground: Noninvasive tests (NITs) to monitor metabolic dysfunction-associated steatohepatitis (MASH) progression and response to interventions are needed because of the risks of liver biopsy. A monocytes-based diagnostic test using perilipin-2 (PLIN2) and Ras-related protein-14 (RAB14) predict the severity of MASH and fibrosis. Here we compared the performances of PLIN2 and RAB14 with cytokeratin-18 (CK18) assessed by Ella™ or M65 ELISA in predicting MASH and fibrosis resolution following bariatric surgery in a longitudinal and histologically characterized cohort of individuals with obesity.
View Article and Find Full Text PDFBackground & Aims: Lipoprotein(a) (Lp(a)) is an emerging biomarker for cardiometabolic factors. We studied the role of Lp(a) in the full spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods: Three independent analyses were implemented using a multi-center, cross-sectional, liver biopsy-based study (n = 332) (Study 1) and the UK Biobank prospective study (n = 270,004) (Study 2; median follow-up, 12.
Dodecanedioic acid (DC12) is a dicarboxylic acid present in protective polymers of fruit and leaves. We explored the effects of DC12 on metabolic dysfunction-associated steatohepatitis (MASH) and obesity. DC12 supplementation (100 mg/kg/day) was added to a high-fat diet (HFD) for 8 weeks in rodents to assess its impact on obesity and MASH prevention.
View Article and Find Full Text PDFBackground: There are no known non-invasive tests (NITs) designed for accurately detecting metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis stages F2-F3, excluding cirrhosis-the FDA-defined range for prescribing Resmetirom and other drugs in clinical trials. We aimed to validate and re-optimize known NITs, and most importantly to develop new machine learning (ML)-based NITs to accurately detect MASH F2-F3.
Methods: Clinical and metabolomic data were collected from 443 patients across three countries and two clinic types (metabolic surgery, gastroenterology/hepatology) covering the entire spectrum of biopsy-proven MASH, including cirrhosis and healthy controls.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohort of histologically characterized individuals with MASL/MASH using stable isotope infusion (6,6-H-glucose, U-H-glycerol) and liver-specific genome-scale metabolic models (GEMs).
View Article and Find Full Text PDFEndoplasmic reticulum (ER) is an essential organelle involved in vesicular transport, calcium handling, protein synthesis and folding, and lipid biosynthesis and metabolism. ER stress occurs when ER homeostasis is disrupted by the accumulation of unfolded and/or misfolded proteins in the ER lumen. Adaptive pathways of the unfolded protein response (UPR) are activated to maintain ER homeostasis.
View Article and Find Full Text PDFBackground & Aims: The available literature on the effect of apolipoprotein C-III (ApoC-III) inhibition in MASLD reveals inconsistencies. The aim of the present work was to examine levels of ApoC-III in the entire spectrum of metabolic-dysfunction associated steatotic liver disease (MASLD).
Methods: This is a multicenter study involving patients enrolled in two gastroenterology-hepatology clinics (Greece and Australia) and in a bariatric-metabolic surgery clinic (Italy), with liver biopsy before and after bariatric surgery or lifestyle modification.
Background: The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity.
Objective: To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues.
Design: Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose).
Multiple myeloma (MM) affects a population with a high prevalence of cardiovascular (CV) disease. These patients benefit from an accurate CV risk evaluation in order to choose the safest drug regimen. Haemodynamic forces (HDFs) analysis allows for the earlier detection of myocardial damage compared with standard markers; the role played by MM in HDFs alteration, with or without the influence of hypertension, is yet to be studied.
View Article and Find Full Text PDFThe global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease.
View Article and Find Full Text PDFThe global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease.
View Article and Find Full Text PDFIn recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases.
View Article and Find Full Text PDFOver the past 40 years, the prevalence of obesity has risen dramatically, reaching epidemic proportions. By 2030 the number of people affected by obesity will reach 1.12 billion worldwide.
View Article and Find Full Text PDFThe burden of chronic metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) and the urgency of the epidemiological situation necessitate the development of therapies that enhance metabolic health and alter the trajectory of metabolic disease in society. Certain bariatric-metabolic surgeries have proven to be effective approaches for treating metabolic dysfunction, showing remission or significant improvements in obesity, T2DM, and MASLD-related outcomes, suggesting that these interventions might be able to "reset" a pathologically calibrated metabolic setpoint. However, considering the challenges and invasiveness of surgery, endoscopic bariatric metabolic therapies (EBMTs) have emerged with a primary focus to reconstruct or mimic anatomical and/or functional changes observed with bariatric surgery in a more broadly accessible manner.
View Article and Find Full Text PDFOver the past 40 years, the prevalence of obesity has risen dramatically, reaching epidemic proportions. Metabolic surgery has proven to be highly effective in treating obesity, leading to significant improvements or complete resolution of obesity-related comorbidities. Research conducted in both animals and humans suggests that the metabolic benefits achieved through metabolic surgery cannot be solely attributed to weight loss.
View Article and Find Full Text PDFBackground And Aims: The duodenum has been shown to play a key role in glucose homeostasis. Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for patients with type 2 diabetes (T2D) in which the duodenal mucosa is hydrothermally ablated. DMR improves glycemic control, but the underlying mechanisms remain unclear.
View Article and Find Full Text PDFBackground And Aims: Thyroid axis is currently under investigation as a therapeutic target in metabolic dysfunction-associated steatotic liver disease (MASLD). Thyroid function was examined herein in the full spectrum of disease.
Methods: Subjects were recruited and had liver biopsies in two Gastroenterology-Hepatology Clinics (Greece and Australia) and one Bariatric-Metabolic Surgery Clinic (Italy).
Background: The role of metabolic/inflammatory hormonal systems in metabolic dysfunction associated steatotic liver disease (MASLD) remains to be fully elucidated.
Purpose: To report the levels of the novel total and H-specific growth differentiation factor-15 (GDF-15) and other established hormonal systems and to describe hormonal patterns in controls and patients with MASLD and its stages.
Methods: This is a multicenter study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy).
Background: Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery.
Methods: In this multinational retrospective observational study we enrolled adult participants (aged ≥18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year follow-up after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band.