Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva.

We investigate the role of homeostatic mechanisms involved in acute, postprandial nutrient metabolism and nutrient-induced systemic inflammation in CKD presence and progression in Metabolic dysfunction-associated steatohepatitis (MASH). We assessed postprandial incretins (GLP-1 and GIP), intestinotropic hormone GLP-2, endotoxin LPS, Zonulin (a marker of intestinal permeability), hepatokines, adipokines and NF-kB activation in circulating MNCs during a meal tolerance test in 52 biopsy proven MASH patients randomized to curcumin Meriva or placebo and 26 matched controls. At baseline, MASH-CKD had a lower GLP-2 response and a 2-fold higher postprandial LPS and NF-kB activation in MNCs than MASH patients without CKD, but similar remaining postprandial or fasting parameters.

Effect of phospholipid curcumin Meriva on liver histology and kidney disease in nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial.

Background And Aims: NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH.

Endoscopic duodenal mucosa ablation techniques for diabetes and nonalcoholic fatty liver disease: A systematic review.

Background: Type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, and only 50% of patients with T2DM achieve or maintain adequate glycemic control with pharmacological therapies. Metabolic surgery demonstrated superior efficacy compared to medical therapy but is unfeasible for most patients with T2DM. Duodenal mucosal resurfacing (DMR) by hydrothermal mucosal ablation, recellularization via electroporation therapy (ReCET), and photodynamic therapy are novel endoscopic procedures that use thermal, electrical, and photochemical energy, respectively, to ablate and reset dysfunctional duodenal mucosa.

In Patients with Obesity, Are Affective Temperaments Associated with Attrition? An Evaluation during and before the SARS-CoV-2 Pandemic.

Timely data on attrition from weight loss programs for patients with obesity during the SARS-CoV-2 pandemic are lacking, so we aimed to contribute to filling this gap in the literature by comparing attrition during or outside of the SARS-CoV-2 pandemic and its possible association with patients' affective temperaments, psychopathology, and clinical variables. Two-hundred and eleven outpatients with obesity were recruited and completed the Temperament Evaluation of Memphis, Pisa, and San Diego Auto-questionnaire, Binge Eating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory. Those who dropped out during the pandemic period were mostly men, with younger age of weight gain, and with a larger waist circumference than completers.

Affective temperaments and obesity: Is there an association with binge eating episodes and multiple weight cycling?

Background: affective temperaments have been so far understudied in the field of obesity. Therefore, we aimed to assess affective temperaments in outpatients with obesity reporting symptoms of binge eating (BE) and multiple weight cycling (MWC) and to investigate the likelihood of an association between affective temperaments and risk of both conditions.

Methods: A total of 300 individuals with obesity seeking treatment at the Obesity Unit of an academic hospital were asked to complete self-report measures of affective temperaments, BE, depressive and anxiety symptoms, and quality of life.

Predictors of attrition from a weight loss program. A study of adult patients with obesity in a community setting.

Purpose: Obesity unit attrition is frequent and contributes to treatment failure. Many studies evaluating attrition predictors were part of randomized trials, and different terminology and criteria were used in the engagement field. We aimed to investigate the factors potentially implicated in early (< 12 weeks) and late (> 12 weeks) attrition from an obesity unit in a community setting METHODS: This was a retrospective cohort study of 250 patients with obesity who were followed-up at our obesity unit.

Changes in Weight and Nutritional Habits in Adults with Obesity during the "Lockdown" Period Caused by the COVID-19 Virus Emergency.

Our aim is evaluating the changes in weight and dietary habits in a sample of outpatients with obesity after 1 month of enforced lockdown during the COVID-19 pandemic in Northern Italy. In this observational retrospective study, the patients of our Obesity Unit were invited to answer to a 12-question multiple-choice questionnaire relative to weight changes, working activity, exercise, dietary habits, and conditions potentially impacting on nutritional choices. A multivariate regression analysis was performed to evaluate the associations among weight/BMI changes and the analyzed variables.

Angiotensin II Type 1 Receptor rs5186 Gene Variant Predicts Incident NAFLD and Associated Hypertension: Role of Dietary Fat-Induced Pro-Inflammatory Cell Activation.

Objectives: Hypertension has been linked to the presence and severity of nonalcoholic fatty liver disease (NAFLD) through unclear mechanisms. The gain-of-function rs5186 A1166C variant in angtiotensin receptor type 1 (AGTR1) gene has been linked to hypertension, cardiovascular disease and metabolic syndrome. We assessed the impact of AGTR1 A1166C variant on NAFLD incidence and severity and on glucose and lipid metabolism and explored the underlying mechanisms.

Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?

Purpose Of Review: In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota.

Recent Findings: In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance.

Gut microbiota, hypertension and chronic kidney disease: Recent advances.

A large number of different microbial species populates intestine. Extensive research has studied the entire microbial population and their genes (microbiome) by using metagenomics, metatranscriptomics and metabolomic analysis. Studies suggest that the imbalances of the microbial community causes alterations in the intestinal homeostasis, leading to repercussions on other systems: metabolic, nervous, cardiovascular, immune.

MERTK rs4374383 variant predicts incident nonalcoholic fatty liver disease and diabetes: role of mononuclear cell activation and adipokine response to dietary fat.

The loss-of-function rs4374383 G > A variant in Myeloid-epithelial-reproductive Tyrosine Kinase (MERTK) gene has been linked to hepatic fibrosis in chronic liver diseases. MERTK is expressed by immune and non-immune cells involved in inflammation, metabolism and vascular homeostasis. We assessed the impact of MERTK rs4374383 G > A variant on nonalcoholic fatty liver disease (NAFLD) incidence and severity and on glucose and lipid metabolism.

An artificial intelligence framework for compensating transgressions and its application to diet management.

Today, there is considerable interest in personal healthcare. The pervasiveness of technology allows to precisely track human behavior; however, when dealing with the development of an intelligent assistant exploiting data acquired through such technologies, a critical issue has to be taken into account; namely, that of supporting the user in the event of any transgression with respect to the optimal behavior. In this paper we present a reasoning framework based on Simple Temporal Problems that can be applied to a general class of problems, which we called cake&carrot problems, to support reasoning in presence of human transgression.

TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD.

Mechanisms underlying the opposite effects of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C>T polymorphism on liver injury and cardiometabolic risk in nonalcoholic fatty liver disease (NAFLD) are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabolism, glucose homeostasis, and nutrient oxidation in NAFLD. Sixty nonobese nondiabetic normolipidemic biopsy-proven NAFLD patients and 60 matched controls genotyped for TM6SF2 C>T polymorphism underwent: indirect calorimetry; an oral fat tolerance test with measurement of plasma lipoprotein subfractions, adipokines, and incretin glucose-dependent insulinotropic polypeptide (GIP); and an oral glucose tolerance test with minimal model analysis of glucose homeostasis.

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities.

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments.

New Pharmacologic Agents That Target Inflammation and Fibrosis in Nonalcoholic Steatohepatitis-Related Kidney Disease.

Epidemiologic data show an association between the prevalence and severity of nonalcoholic fatty liver disease and the incidence and stage of chronic kidney disease (CKD); furthermore, nonalcoholic steatohepatitis (NASH)-related cirrhosis has a higher risk of renal failure, a greater necessity for simultaneous liver-kidney transplantation, and a poorer renal outcome than cirrhosis of other etiologies even after simultaneous liver-kidney transplantation. These data suggest that NASH and CKD share common proinflammatory and profibrotic mechanisms of progression, which are targeted incompletely by current treatments. We reviewed therapeutic approaches to late preclinical/early clinical stage of development in NASH and/or CKD, focusing on anti-inflammatory and antifibrotic treatments, which could slow the progression of both disease conditions.

Impact of snacking pattern on overweight and obesity risk in a cohort of 11- to 13-year-old adolescents.

Objectives: The association between snacking habits and overweight in adolescents is unclear. We evaluated the relation between snacking patterns and overweight/obesity in a cohort of 11- to 13-year-old Italian adolescents.

Methods: The dietary habits of 400 randomly selected adolescents were evaluated; those with body mass index ≥ 85 th percentile were considered as overweight/obese.

Impact of sterol regulatory element-binding factor-1c polymorphism on incidence of nonalcoholic fatty liver disease and on the severity of liver disease and of glucose and lipid dysmetabolism.

Background: Genetic factors that predispose individuals to nonalcoholic fatty liver disease (NAFLD) and associated diabetes and cardiovascular disease are unclear. The transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) modulates lipogenesis and insulin sensitivity and was experimentally connected to NAFLD.

Objective: We assessed the impact of a common SREBF-1c polymorphism on the incidence and severity of NAFLD and on associated glucose and lipoprotein dysmetabolism.

Sterol regulatory element-binding factor 2 (SREBF-2) predicts 7-year NAFLD incidence and severity of liver disease and lipoprotein and glucose dysmetabolism.

We prospectively assessed the impact of a sterol regulatory element-binding factor-2 (SREBF-2) polymorphism on the risk of developing nonalcoholic fatty liver disease (NAFLD) and on liver histology and lipoprotein and glucose metabolism in biopsy-proven NAFLD. In a population-based study, we followed 175 nonobese, nondiabetic participants without NAFLD or metabolic syndrome at baseline, characterized for the SREBF-2 rs133291 C/T polymorphism, dietary habits, physical activity, adipokines, C-reactive protein (CRP), and endothelial adhesion molecules. A comparable cohort of NAFLD patients underwent liver biopsy, an oral glucose tolerance test with minimal model analysis to yield glucose homeostasis parameters, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, and cytokeratin-18 fragments.

Nonalcoholic steatohepatitis versus steatosis: adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism.

Unlabelled: Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). Though liver-related risk seems confined to NASH, it is currently unclear whether NASH has a higher risk of cardiovascular disease (CVD) and diabetes than SS as a result of the coexistence of obesity and other cardiometabolic confounders. Adipose tissue is an emerging modulator of liver disease in NAFLD and of cardiometabolic disease in the general population.

Effect of lectin-like oxidized LDL receptor-1 polymorphism on liver disease, glucose homeostasis, and postprandial lipoprotein metabolism in nonalcoholic steatohepatitis.

Background: Nonalcoholic steatohepatitis (NASH) affects 3-5% of the general adult population and predisposes to cirrhosis, cardiovascular disease (CVD), and diabetes through unclear mechanisms. Lectin-like oxidized LDL receptor-1 (LOX-1) has been connected to CVD risk in the general population and to insulin resistance and hepatic fibrogenesis in experimental models.

Objective: The objective was to assess the effect of the common functional LOX-1 IVS4-14 A→G polymorphism on liver disease, adipokines, oxidative stress, lipoprotein metabolism, and glucose homeostasis in NASH.

Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver.

Background: Genetic and acquired mechanisms underlying the association of nonalcoholic fatty liver disease (NAFLD) with diabetes are unknown. Glucose-dependent insulinotropic polypeptide (GIP) was recently linked to adipocyte metabolism and obesity-related metabolic disorders, including NAFLD, induced by an excess of saturated fatty acids (SFAs), but its role in vivo, as well as underlying mechanisms, is unknown. We hypothesized that altered GIP secretion may contribute to the pathogenesis of NAFLD.

Association of liver disease with postprandial large intestinal triglyceride-rich lipoprotein accumulation and pro/antioxidant imbalance in normolipidemic non-alcoholic steatohepatitis.

Background: Dietary fat excess and antioxidant deficiency, altered lipid metabolism, and increased lipoperoxidation have been associated with non-alcoholic steatohepatitis (NASH), but the relative importance of each of these factors is unclear.

Aims: To assess acute intestinal and hepatic very-low-density lipoprotein (VLDL) subfraction metabolism, lipid peroxidation, and pro/antioxidant imbalance after a fat load in NASH.

Methods: Dietary habits, circulating adipokines, fasting and postprandial lipids, intestinal and hepatic VLDL, oxidized low-density lipoproteins (oxLDL), and total antioxidant status (TAS) were correlated to postprandial liver enzymes and to liver histology in 28 non-obese non-diabetic normolipidemic patients with NASH and 28 healthy controls.

Adiponectin gene polymorphisms modulate acute adiponectin response to dietary fat: Possible pathogenetic role in NASH.

Unlabelled: Factors underlying the independent association of nonalcoholic steatohepatitis (NASH) with increased cardiovascular risk are unknown. Adiponectin polymorphisms predict cardiometabolic risk in the general population. This association is not always mediated by low fasting adiponectin levels, adipose tissue accumulation, or traditional risk factors.