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

BACKGROUND AIMS: Nonalcoholic steatohepatitis (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 safety and efficacy of Meriva ® in NASH. APPROACH: In this double-blind trial, 52 biopsy-proven NASH patients(71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a CKD) were randomized 1:1 to receive Meriva ® 2 g/day or placebo for 72 weeks. Primary end-point was NASH resolution with no worsening of fibrosis. Secondary end-points included: a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant(i.e. stage≥F2) fibrosis and of chronic kidney disease(CKD); improvement in renal, glucose, lipid and inflammatory parameters. We also explored treatment effect on hepatic activation of Nuclear Factor(NF)-kB, a key proinflammatory transcription factor and a major target of curcumin. RESULTS: Fifty-one patients(26 on Meriva ® and 25 on placebo) completed the trial. Sixteen(62%) patients on Meriva ® vs. three(12%) patients on placebo had NASH resolution(RR=5.33[95%CI=1.76-12.13]; p=0.003). Thirteen(50%) patients on Meriva ® vs. 2(8%) patients on placebo had ≥1 stage fibrosis improvement(RR=6.50[(1.63-21.20]; p=0.008). Eleven(42%) patients on Meriva ® vs. 0(0%) on placebo had regression of significant liver fibrosis(RR=18.01[1.43-36.07]; p=0.02). Hepatic NF-kB inhibition predicted NASH resolution(AUC=0.90,95%CI=0.84-0.95) and fibrosis improvement(AUC=0.89,95%CI=0.82-0.96). Thirteen(50%) patients on Meriva ® vs. 0(0%) on placebo had CKD regression(RR=10.71[1.94-17.99)]; p=0.004). Compared with placebo, Meriva ® improved eGFR(difference in adjusted eGFR change: +3.59[2.96-4.11] mL/min/1.73 m 2 /year, p =0.009), fasting glucose(-17 mg/dL;95%CI=-22, -12), HbA1c(-0.62%;95%CI=-0.87%, -0.37%), LDL-C(-39 mg/dL; 95%CI=-45, -33), triglycerides(-36 mg/dL, 95%CI= -46, -26), HDL-C(+10 mg/dL; 95%CI=+8, +11) and inflammatory markers. Adverse events were rare, mild and evenly distributed. CONCLUSION: In NASH patients, Meriva ® administration for 72 weeks was safe, well-tolerated, improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile.

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. Our program included at least 6 meetings in 12 months. Sociodemographic and anthropometric data, and psychometric questionnaires were collected from all participants. RESULTS: One-hundred thirty-four (53.6%) participants dropped out. Those individuals showed lower BMI, lower overall health status, and increased depression scores. In a multiple regression model, BMI (inversely; OR = 0.90; 95%CI 0.84-0.96) and depression score (directly, OR = 1.05; 1.00-1.10) were associated with attrition risk. Early dropouts (n = 47) had lower weights, smaller waist circumferences and worse mental health scores than late dropouts (n = 87) and more frequently lived alone. When compared to completers, early dropouts had lower weights, BMIs, waist circumferences, overall health and mental status scores, increased depression scores and percentage of individuals living alone. In a multiple regression, lower BMI (OR = 0.83; 0.75-0.92), lower mental status score (OR = 3.17; 1.17-8.59) and living alone (OR = 2.25; 1.02-4.97) were associated with early attrition risk. CONCLUSION: Lower BMI and increased depression score were associated with attrition. Early attrition was associated with lower weight, decreased mental well-being, and living alone. Individuals with these characteristics might need tailored approaches to enhance their engagement. LEVEL OF EVIDENCE: Level V, retrospective descriptive study.

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. We followed-up 305 healthy nonobese nondiabetic, metabolic syndrome-free insulin sensitive participants in a population-based study, characterized for MERTK G > A polymorphism, adipokine profile and inflammatory markers.An independent cohort of 69 biopsy-proven nondiabetic NAFLD patients and 69 healthy controls underwent indirect calorimetry, an OGTT with Minimal Model analysis of glucose homeostasis, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, MCP-1, and of Nuclear Factor (NF)-κB activation in circulating mononuclear cells (MNCs). In the longitudinal cohort, MERTK G > A polymorphism protected against 9-year incident NAFLD (OR:0.48,95%CI:0.26-0.79) and diabetes (OR: 0.47, 95% CI: 0.19-0.87).In the cross-sectional cohort, MERTK A-allele carriers had higher fat oxidation rates and tissue insulin sensitivity. Despite comparable fastign and postprandial lipid profiles, MERTK A-allele carriers showed lower resistin and MCP-1 responses, milder MNC NF-κB activation, and a higher postprandial adiponectin response to fat, which predicted tissue insulin resistance hepatocyte apoptosis and liver histology. MERTK G > A variant affects liver disease, nutrient oxidation and glucose metabolism in NAFLD. The modulation of adipokine, chemokine and pro-inflammatory MNC activation in response to fat ingestion may contribute to the observed effects on liver and metabolic disease.

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. METHODS: We followed up 314 healthy nonobese, nondiabetic, nonhypertensive, insulin-sensitive participants in a population-based study, characterized for AGTR1 rs5186 A1166C variant, adipokine profile, inflammatory and endothelial dysfunction markers. An independent cohort of 78 biopsy-proven nondiabetic NAFLD patients and controls underwent an oral glucose tolerance test with Minimal Model analysis of glucose homeostasis, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, MCP-1, calprotectin, and nuclear factor-κB activation in circulating mononuclear cells. RESULTS: AGTR1 A1166C polymorphism predicted 9.8-year incident NAFLD (odds ratio: 1.67, 95% CI: 1.26-2.21) and hypertension (odds ratio: 1.49, 95% CI: 1.12-2.63) and 9-year increase in cardiovascular disease risk and endothelial dysfunction markers. In the cross-sectional cohort, AGTR1 C allele carriers had higher insulin resistance. Despite comparable fasting lipid profiles, AGTR1 C allele carriers showed postprandial triglyceride-rich and cholesterol-rich VLDL lipoprotein accumulation, higher resistin, MCP-1 and calprotectin responses and nuclear factor-κB activation in mononuclear cells, and a blunted postprandial adiponectin response to fat, which predicted liver histology, hepatocyte apoptosis activation, insulin resistance, and endothelial dysfunction. DISCUSSION: AGTR1 A1166C variant affects liver disease, insulin resistance, and endothelial dysfunction in NAFLD, at least in part by modulating adipokine, chemokine, and pro-inflammatory cell activation in response to fat ingestion.

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. These studies have also shown that alterations in the structure and function of the gut microbiota play a key role in the pathogenesis and complications of Hypertension (HTN) and Chronic Kidney Disease (CKD). Increased blood pressure (BP) and CKD are two leading risk factors for cardiovascular disease and their treatment represents a challenge for the clinicians. In this Review, we discuss mechanisms whereby gut microbiota (GM) and its metabolites act on downstream cellular targets to contribute to the pathogenesis of HTN and CKD, and potential therapeutic implications.

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. Different strategies that reduce dysbiosis can improve glycemic control. Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.

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. The TM6SF2 T-allele was associated with higher hepatic and adipose insulin resistance, impaired pancreatic ß-cell function and incretin effect, and higher muscle insulin sensitivity and whole-body fat oxidation rate. Compared with the TM6SF2 C-allele, the T-allele entailed lower postprandial lipemia and nefaemia, a less atherogenic lipoprotein profile, and a postprandial cholesterol (Chol) redistribution from smaller atherogenic lipoprotein subfractions to larger intestinal and hepatic VLDL1 subfractions. Postprandial plasma VLDL1-Chol response independently predicted the severity of liver histology. In conclusion, the TM6SF2 C>T polymorphism affects nutrient oxidation, glucose homeostasis, and postprandial lipoprotein, adipokine, and GIP responses to fat ingestion independently of fasting values. These differences may contribute to the dual and opposite effect of this polymorphism on liver injury and cardiometabolic risk in NAFLD.

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. Renin inhibitors and angiotensin-converting enzyme-2 activators are new renin-angiotensin axis modulators that showed incremental advantages over angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers in preclinical models. Novel, potent, and selective agonists of peroxisome proliferator-activated receptors and of farnesoid X receptor, designed to overcome limitations of older compounds, showed promising results in clinical trials. Epigenetics, heat stress response, and common effectors of redox regulation also were subjected to intensive research, and the gut was targeted by several approaches, including synbiotics, antilipopolysaccharide antibodies, Toll-like receptor-4 antagonists, incretin mimetics, and fibroblast growth factor 19 analogs. Promising anti-inflammatory therapies include inhibitors of NOD-like receptor family, pyrin domain containing 3 inflammasome, of nuclear factor-κB, and of vascular adhesion protein-1, chemokine antagonists, and solithromycin, and approaches targeting common profibrogenic pathways operating in the liver and the kidney include galectin-3 antagonists, and inhibitors of rho-associated protein kinase and of epidermal growth factor activation. The evidence, merits, and limitations of each approach for the treatment of NASH and CKD are discussed.

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. The reasoning framework offers a number of facilities to ensure a smart management of possible "wrong behaviors" by a user to reach the goals defined by the problem. This paper describes the framework by means of the prototypical use case of diet domain. Indeed, following a healthy diet can be a difficult task for both practical and psychological reasons and dietary transgressions are hard to avoid. Therefore, the framework is tolerant to dietary transgressions and adapts the following meals to facilitate users in recovering from such transgressions. Finally, through a simulation involving a real hospital menu, we show that the framework can effectively achieve good results in a realistic scenario.

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. Participants were classified based on the percentage of caloric intake from snacks (<15%, 15%-20%, >20%), snacking frequency (1, 2, ≥ 3), and timing of consuming the most caloric snack (morning, afternoon, evening). RESULTS: A minority of participants (13/400, 3.3%) did not consume any snacks; 5/13 (38.5) of them were overweight/obese. Among snackers (387/400), overweight/obesity prevalence was 10.4%, 14.4%, 20.5%, respectively, in those consuming <15%, 15% to 10%, and >20% of their energy intake from snacks. In a Poisson regression model, the overweight/obesity relative risks (RRs) were 1.35 (95% confidence interval [CI] 0.58-3.15) and 2.32 (1.10-4.89) for 15% to 20% and >20% calories/day from snacks, respectively. Overweight/obesity prevalence (from 9.6% to 22.6%) was correlated with snacking frequency (RR 2.20, 95% CI 0.92-5.27, and RR 4.17, 95% CI 1.60-10.9, for 2 and ≥ 3 snacks per day, respectively). The most caloric snacks were consumed in the morning (180/387) and afternoon (179/387); 28.6% of the predominantly evening snackers (28/387) were overweight/obese (RR 3.12, 95% CI 1.17-8.34). CONCLUSIONS: Increased snacking calories, frequency, and evening snacking are independently associated with overweight/obesity in Italian middle-school adolescents.

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. We assessed the data on the effects of these techniques on glycemic control and nonalcoholic fatty liver disease (NAFLD). METHODS: We systematically searched independently and in duplicate English and non-English language publications through January 31st, 2024. Outcomes assessed were an improvement in different metabolic health parameters and the safety of duodenal mucosal ablation (DMA) procedures. Outcomes were presented descriptively. FINDINGS: We selected 12 reports reporting results from 3 randomized and 6 uncontrolled trials (seven evaluating DMR, two evaluating ReCET, all with a low risk of bias) for a total of 317 patients enrolled. DMA reduced HbA1c, fasting plasma glucose, and liver fat. When combined with newer antidiabetic drugs, it allowed insulin discontinuation in up to 86% patients. No major safety signal emerged. CONCLUSIONS: All DMA techniques improve glucose homeostasis; DMR and ReCET appear to be safe in patients with T2DM. If confirmed by future randomized trials and by trials with histological endpoints in NAFLD, then DMA appears to be a promising alternative or complement option to medications for T2DM and NAFLD treatment. FUNDING: This study received no funding.

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. We evaluated in SS and NASH (1) glucose homeostasis and cardiovascular risk profile and (2) the effect of adipose tissue dysfunction, assessed in fasting conditions and postprandially, on liver injury, glucose and lipoprotein metabolism, and markers of early atherosclerosis. Forty nonobese, nondiabetic, normolipidemic biopsy-proven NAFLD patients (20 with SS and 20 with NASH) and 40 healthy subjects, matched for overall/abdominal adiposity and metabolic syndrome, underwent an oral fat load test, with measurement of plasma triglyceride-rich lipoproteins, oxidized low-density lipoproteins, adipokines, and cytokeratin-18 fragments, and an oral glucose tolerance test with minimal model analysis to yield glucose homeostasis parameters. Circulating endothelial adhesion molecules were measured, and adipose tissue insulin resistance (adipose IR) index and visceral adiposity index were calculated. Despite similar fasting values, compared to SS, NASH showed a more atherogenic postprandial lipoprotein profile, an altered adipokine response (i.e., higher resistin increase and an adiponectin fall), and hepatocyte apoptosis activation after fat ingestion. Adipose IR index, endothelial adhesion molecules, and hepatic insulin resistance progressively increased across NAFLD stages. NASH, but not SS, showed an impaired pancreatic ß-cell function. On multiple regression analysis, adipose IR index and postprandial adiponectin independently predicted liver histology and altered cardiometabolic parameters. CONCLUSION: Adipose tissue dysfunction, including a maladaptive adipokine response to fat ingestion, modulates liver injury and cardiometabolic risk in NAFLD.

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. Patients with obesity who dropped out outside of the SARS-CoV-2 pandemic showed marked levels of depression, anxiety, binge eating episodes, and higher affective temperaments (but the hyperthymic one) when compared to their counterparts. The cyclothymic temperament slightly increased attrition (OR = 1.13, 95% CI 1.00-1.27 p = 0.05) outside the pandemic, while during the pandemic, male gender (OR = 3.50, 1.04-11.7, p = 0.04) was associated with attrition. These findings suggested that male patients with obesity are at particular risk of drop-out from weight-loss treatment during the SARS-CoV-2 pandemic; contrariwise, outside the pandemic, affective temperaments could be a useful baseline assessment for defining the attrition risk in these patients.

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. RESULTS: Even in the absence of full-blown mental disorders, symptoms of anxiety and depression emerged in the sample; 197 individuals (65.6%) reported BE and 162 (54%) MWC. The most frequent affective temperament was the depressive one. Depression symptoms and cyclothymic scores (directly), and age and hyperthymic score (inversely) were significantly associated with BE risk, while being an active smoker (directly) and hyperthymic score (inversely) were significantly associated with MWC risk, after controlling for confounders in a multiple logistic regression. LIMITATIONS: sample size was small, the study was limited to a single center, no formal definition of weight cycling exists and MWC was self-reported. CONCLUSIONS: A substantial number of outpatients with obesity reported BE and MWC notwithstanding the absence of a formal psychiatric diagnosis. Cyclothymic scores were positively associated with BE while the hyperthymic temperament showed a protective effect on both BE and MWC. These findings suggest the need for multidisciplinary treatments for people with obesity enhancing research on temperament-based psychological interventions.

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. A total of 150 subjects (91.5%) completed the questionnaire. Mean self-reported weight gain was ≈1.5 kg (p < 0.001). Lower exercise, self-reported boredom/solitude, anxiety/depression, enhanced eating, consumption of snacks, unhealthy foods, cereals, and sweets were correlated with a significantly higher weight gain. Multiple regression analyses showed that increased education (inversely, ß = -1.15; 95%CI -2.13, -0.17, p = 0.022), self-reported anxiety/depression (ß = 1.61; 0.53, 2.69, p = 0.004), and not consuming healthy foods (ß = 1.48; 0.19, 2.77, p = 0.026) were significantly associated with increased weight gain. The estimated direct effect of self-reported anxiety/depression on weight was 2.07 kg (1.07, 3.07, p < 0.001). Individuals with obesity significantly gained weight 1 month after the beginning of the quarantine. The adverse mental burden linked to the COVID-19 pandemic was greatly associated with increased weight gain.

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. Adiponectin modulates lipid metabolism and liver injury in nonalcoholic fatty liver disease (NAFLD) even in the absence of obesity, dyslipidemia, and diabetes. We hypothesized adiponectin polymorphisms may predispose to NAFLD and may increase cardiovascular risk by modulating circulating lipoprotein and adiponectin response postprandially. The prevalence of adiponectin single-nucleotide polymorphisms (SNPs) 45GT and 276GT was assessed in 70 nonobese, nondiabetic, normolipidemic NAFLD patients and 70 healthy matched controls; the impact of the adiponectin SNPs was subsequently correlated to liver histology and postprandial adiponectin and lipoprotein responses to oral fat load in a subgroup of 30 biopsy-proven patients with NASH and 30 controls. The 45TT and 276GT/TT genotypes were more prevalent in NAFLD patients than in controls and independently predicted the severity of liver disease in NASH. In both patients and controls, these genotypes exhibited a blunted postprandial adiponectin response and higher postprandial triglycerides (Tg), free fatty acids (FFA), oxidized LDL (oxLDL), and VLDL levels than their counterparts, despite comparable fasting adipokines, lipids, dietary habits, adiposity, and insulin resistance. They were also independently associated, together with dietary polyunsaturated fatty acid intake, with postprandial adiponectin response. IAUC adiponectin independently predicted postprandial Tg, FFA, oxLDL, and intestinal and hepatic VLDL subfraction responses in NASH. CONCLUSION: The at-risk adiponectin SNPs 45TT and 276GT are significantly more prevalent in NAFLD than in the general population; they are associated with severity of liver disease, with blunted postprandial adiponectin response, and with an atherogenic postprandial lipoprotein profile in NASH independently of fasting adipokine and lipid levels.

Nitrosative stress predicts the presence and severity of nonalcoholic fatty liver at different stages of the development of insulin resistance and metabolic syndrome: possible role of vitamin A intake.

BACKGROUND: Although nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome, the mechanisms responsible for the development of NAFLD at different stages of the development of insulin resistance are unknown. Diet, adipokines, and nitrosative stress have been linked to both NAFLD and insulin resistance. OBJECTIVE: We aimed to identify the factors that are specifically associated with NAFLD at different stages in the development of insulin resistance and the metabolic syndrome. DESIGN: Circulating concentrations of adipokines (ie, tumor necrosis factor-alpha, adiponectin, resistin, leptin, and interleukin-6), markers of nitrosative stress (nitrotyrosine), dietary habits, and MTP -493G/T polymorphism were cross-sectionally related to the presence and severity of insulin resistance (homeostasis model assessment index for insulin resistance: >or=2), the metabolic syndrome, and fatty liver in 64 nonobese nondiabetic patients with NAFLD (33 insulin-sensitive and 31 insulin-resistant subjects) and 74 control subjects without liver disease who were matched for sex, BMI, homeostasis model assessment index for insulin resistance status, and the various features of the metabolic syndrome. RESULTS: Persons with NAFLD had greater systemic nitrosative stress and a lower intake of vitamins A and E than did control subjects, but the 2 groups did not differ significantly in any other features. Nitrotyrosine and adiponectin concentrations and vitamin A intakes independently predicted alanine aminotransferase concentrations in NAFLD patients and liver histology in a subgroup of 29 subjects with biopsy-proven nonalcoholic steatohepatitis. CONCLUSIONS: Oxidative stress is operating in NAFLD and nonalcoholic steatohepatitis, even in the absence of insulin resistance, the metabolic syndrome, and hypoadiponectinemia, which aggravate liver histology at more severe stages of metabolic disease. The possible pathogenetic role of reduced vitamin A intake in NAFLD warrants further investigation.

Magnesium intake, glucose and insulin serum levels in pre-school very-low-birth weight pre-term children.

AIMS: To evaluate cross-sectional associations between dietary magnesium intake and the metabolic pattern of very-low-birth-weight (VLBW, <1500 g) pre-term children, in pre-school years (>2 and <6 years). METHODS AND RESULTS: Fifty-eight Italian children without major congenital malformations/conditions were enrolled; dietary intakes, clinical and (in 34 cases) laboratory characteristics were evaluated. Subjects with lower magnesium intake showed significantly higher fasting glucose, insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels. At simple regression analysis, fasting glucose was significantly associated with magnesium intake (inversely) and catch-up growth (CUG). Fasting insulin and HOMA-IR values were inversely associated with intakes of magnesium and fibres, and directly with Body Mass Index (BMI) and CUG. In a multiple regression model, after adjusting for multiple confounders and fibre intake, magnesium intake was inversely associated with glucose (beta=-0.018; 95%CI -0.026 to -0.010), but not with insulin or HOMA-IR levels. In the same model, dietary fibres remained inversely associated with insulin (beta=-0.075; -0.14 to -0.008) and HOMA-IR levels (beta=-0.06; -0.11 to -0.01). CONCLUSION: These results suggest a significant association between reduced magnesium intake and fasting glucose, and between reduced fibre intake and insulin resistance and this is present even in earlier childhood, and independently of BMI and growth characteristics.

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. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferator-activated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium.