Melania Gaggini - Academia.edu (original) (raw)

Papers by Melania Gaggini

Research paper thumbnail of Adverse impact of visceral fat on lipid and metabolic profile in fatty liver disease

51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), 2015

Research paper thumbnail of Evaluation of Published Clinical Scores for the Prediction of Cardiometabolic Risk in the SEMEOTICONS Project

Proceedings of the International Conference on Health Informatics, 2014

Cardiovascular and metabolic diseases are the major causes of morbidity and mortality in the West... more Cardiovascular and metabolic diseases are the major causes of morbidity and mortality in the Western Countries. Metabolic syndrome (defined as 3 out of 5 factors among increased waist circumference, hypertension, high blood glucose, high triglyceride and low high density lipoprotein (HDL) cholesterol concentrations) is associated with increased cardiometabolic risk. Other indexes have been proposed and validated, based on the measurement of plasma concentration of lipids, glucose and liver enzymes. In the SEMEOTICONS project we plan to measure parameters related to increased cardiometabolic risk, e.g. skin accumulation of cholesterol and advanced glycated end products, liver enzyme alteration by changing in skin and eye color and obesity. The results will allow to evaluate cardiometabolic risk using non invasive clinical parameters. The new score obtained will be compared with previously validated indexes. In this paper we have evaluated the most common cardiometabolic risk scores i.e., VAI (Visceral Adiposity Index), HTG-Waist (Hypertriglyceridemic Waist), FLI (Fatty Liver Index) and LAP (Lipid Accumulation Product), that we will use during the project.

Research paper thumbnail of Changes in Plasma Bioactive Lipids and Inflammatory Markers during a Half-Marathon in Trained Athletes

Applied Sciences, 2021

Background: Exercise may affect lipid profile which in turn is related to inflammation, although ... more Background: Exercise may affect lipid profile which in turn is related to inflammation, although changes of ceramides, diacylglycerols-DAG and sphingomyelin-SM and their relationship with inflammatory parameters following a half-marathon have never been examined. Methods: Ceramides, DAG and SM, and markers of inflammation (soluble fractalkine-CX3CL1, vascular endothelial growth factor-VEGF, interleukin6-IL-6 and tumor necrosis factorα-TNFα) were evaluated in trained half-marathoners before, post-race (withdrawal within 20 min after the race end) and 24 h after. Results: IL-6 and CX3CL1 increased immediately after the race, returning to baseline after 24 h. Total ceramides and total DAG significantly decreased post-race. Several ceramide classes decreased after exercise, while only one of the DAG (36:3) changed significantly. Total SM and specific species did not significantly change. Conclusion: Some inflammatory parameters (IL-6 and CX3CL1) transiently increased after the race, and...

Research paper thumbnail of Biomonitoring of Bis(2-ethylhexyl)phthalate (DEHP) in Italian children and adolescents: Data from LIFE PERSUADED project

Environmental Research, 2020

The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disru... more The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disrupting chemical with main toxicological effects on reproductive and metabolic systems. Human biomonitoring (HBM) studies are promoted to evaluate the background exposure levels. In the frame of LIFE PERSUADED project, the HBM study measured DEHP main metabolites (mono-(2-ethylhexyl) phthalate, MEHP; 2-ethyl-5-hydroxy-hexylphthalate, MEHHP; 2-ethyl-5-oxo-hexylphthalate, MEOHP) in Italian children and adolescent (4-14 years old) according to geographical macro-areas and areas, age and sex. Children from the South and the Centre of Italy showed higher median levels of DEHP, as a sum of its metabolites (48.14 and 47.80 μg/L), than those from the North (39.47 μg/L; p = 0.0090 and 0.0004, respectively). Considering the total population, boys are more exposed than girls (only as urinary volume), and children aged 4-6 years have higher median levels than those 7-10 and 11-14 years old. The derived reference values (RV95) for DEHP in children is 168 μg/L. The relative metabolic rates of DEHP, the background levels and, thus, the RV95, vary with the geographical area, age and sex, indicating that all these parameters should be considered in the risk assessment. leach out of the products and migrate into soils, surface water, sediments, indoor air and foodstuff during processing, packaging and storage phases leading to a widespread human exposure (Pakalin et al., 2008). In 2005, the European Food Safety Authority (EFSA) stated that food contamination is the main source of exposure in the general population and reiterated that DEHP is of concern for its toxicological

Research paper thumbnail of Author Correction: Lack of NLRP3-inflammasome leads to gut-liver axis derangement, gut dysbiosis and a worsened phenotype in a mouse model of NAFLD

Scientific reports, Jan 11, 2017

A correction to this article has been published and is linked from the HTML version of this paper... more A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Research paper thumbnail of Increased hepatic glucose production and insulin resistance are associated to increased plasma concentrations of glucogenic amino acids in subjects with NAFLD

Digestive and Liver Disease, 2017

Research paper thumbnail of Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance

Research paper thumbnail of Lack of NLRP3-inflammasome leads to gut-liver axis derangement and increases hepatic injury in a mouse model of NAFLD

Digestive and Liver Disease, 2016

Research paper thumbnail of Angiopoietin-like4 is associated with lipid metabolism and severe fibrosis in non-diabetic patients with non-alcoholic fatty liver disease

Digestive and Liver Disease, 2016

Research paper thumbnail of The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis

Nutrients, 2015

Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in met... more Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC). The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance. The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance, such as type 2 diabetes and non alcoholic fatty liver disease.

Research paper thumbnail of Peripheral insulin resistance predicts liver damage in nondiabetic subjects with nonalcoholic fatty liver disease

Hepatology, 2015

Surrogate indexes of insulin resistance/sensitivity (IR/IS) are widely used in Non Alcoholic Fatt... more Surrogate indexes of insulin resistance/sensitivity (IR/IS) are widely used in Non Alcoholic Fatty Liver Disease (NAFLD) although they have never been validated in this population. We aimed to validate the available indexes in NAFLD subjects and to test their ability to predict liver damage also in comparison with NAFLD Fibrosis Score (NFS). Surrogate indexes were validated by tracer technique (D2-glucose and U-13C-glucose) in the basal state and during an Oral Glucose Tolerance Test (OGTT). The best performing indexes were used in an independent cohort of 145 non-diabetic NAFLD subjects to identify liver damage (fibrosis and NASH). In the validation NAFLD cohort, HOMA-IR, IGR and ISI Stumvoll had the best association with hepatic IR, while peripheral IS was most significantly related to OGIS, ISI Stumvoll and eMCR(nodem) . In the independent cohort, only OGTT derived indexes were associated with liver damage and OGIS was the best predictor of significant (≥F2) fibrosis (OR=0.76, 95% CI= 0.61-0.96, P=0.0233) and of NASH (OR=0.75, 95% CI=0.63-0.90, P=0.0021). Both OGIS and NFS identified advanced (F3/F4) fibrosis, but OGIS predicted it better than NFS (OR=0.57, 95% CI=0.45-0.72, P<0.001) and was also able to discriminate F2 from F3/F4 (P<0.003). OGIS is associated with peripheral IS in NAFLD and is inversely associated with an increased risk of significant/advanced liver damage in non-diabetic subjects with NAFLD. This article is protected by copyright. All rights reserved.

Research paper thumbnail of P0519 : Lipidomics reveals that low plasma unsaturated to saturated fat ratios are biomarkers of NAFLD and liver damage

Journal of Hepatology, 2015

Research paper thumbnail of O064 : Gut-liver axis derangement due to lack of inflammasome activity leads to visceral obesity and nash development

Journal of Hepatology, 2015

Research paper thumbnail of Liver damage can be associated with deregulation of the de novo lipogenesis pathway in subjects with Non Alcoholic Fatty Liver Disease

Digestive and Liver Disease, 2015

Research paper thumbnail of Validation of surrogate indexes of peripheral and hepatic insulin resistance and evaluation of their utility as non-invasive predictors of histological features in patients with Non-Alcoholic Fatty Liver Disease

Research paper thumbnail of Gut–liver axis derangement due to lack of inflammasome activity leads to visceral obesity and NASH development

Digestive and Liver Disease, 2015

Research paper thumbnail of Ectopic fat: the true culprit linking obesity and cardiovascular disease?

Thrombosis and Haemostasis, 2013

SummaryObesity is a major risk factor for cardiovascular disease and its complications. However, ... more SummaryObesity is a major risk factor for cardiovascular disease and its complications. However, not all fat depots share the same characteristics. Recent studies have found that ectopic rather than subcutaneous fat accumulation is associated with increased cardiometabolic risk. However, ectopic fat accumulation can be seen initially as a protective mechanism against lipotoxicity. Subsequently the adipose tissue becomes dysfunctional, thus inducing systemic metabolic alterations (through release of cytokines) or specific organ dysfunctions. The purpose of this review is to summarise the current available data on the impact of excess adiposity vs ectopic fat in the development of cardiometabolic diseases.

Research paper thumbnail of Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease

Nutrients, 2013

Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse.... more Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs). The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease.

Research paper thumbnail of P849 Quantitative and Qualitative Analysis of Plasma Free Fatty Acids and Their Impact on Liver Damage in Nafld Patients

Journal of Hepatology, 2014

Research paper thumbnail of P843 Alteration in Glucose Metabolism After an Oral Glucose Load and Relationship with Liver Damage in Patients with Nafld

Journal of Hepatology, 2014

P840 ALTERATION IN LIPID METABOLISM AFTER AN ORAL FAT LOAD IN PATIENTS WITH NAFLD L. Mezzabotta, ... more P840 ALTERATION IN LIPID METABOLISM AFTER AN ORAL FAT LOAD IN PATIENTS WITH NAFLD L. Mezzabotta, E. Vanni, C. Rosso, M. Gaggini, R. Gambino, E. Buzzigoli, C. Saponaro, D. Ciociaro, M.L. Abate, F. Saba, F. Salomone, G.P. Caviglia, S. Carenzi, A. Smedile, M. Rizzetto, M. Cassader, A. Gastaldelli, E. Bugianesi. Medical Sciences, University of Turin, Turin, Cardiometabolic Risk Unit, Institute of Clinical Physiology – CNR, Pisa, U.O.C. of Gastroenterology, Azienda Sanitaria Provinciale di Catania, Catania, Italy E-mail: laviniaemme@hotmail.com

Research paper thumbnail of Adverse impact of visceral fat on lipid and metabolic profile in fatty liver disease

51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), 2015

Research paper thumbnail of Evaluation of Published Clinical Scores for the Prediction of Cardiometabolic Risk in the SEMEOTICONS Project

Proceedings of the International Conference on Health Informatics, 2014

Cardiovascular and metabolic diseases are the major causes of morbidity and mortality in the West... more Cardiovascular and metabolic diseases are the major causes of morbidity and mortality in the Western Countries. Metabolic syndrome (defined as 3 out of 5 factors among increased waist circumference, hypertension, high blood glucose, high triglyceride and low high density lipoprotein (HDL) cholesterol concentrations) is associated with increased cardiometabolic risk. Other indexes have been proposed and validated, based on the measurement of plasma concentration of lipids, glucose and liver enzymes. In the SEMEOTICONS project we plan to measure parameters related to increased cardiometabolic risk, e.g. skin accumulation of cholesterol and advanced glycated end products, liver enzyme alteration by changing in skin and eye color and obesity. The results will allow to evaluate cardiometabolic risk using non invasive clinical parameters. The new score obtained will be compared with previously validated indexes. In this paper we have evaluated the most common cardiometabolic risk scores i.e., VAI (Visceral Adiposity Index), HTG-Waist (Hypertriglyceridemic Waist), FLI (Fatty Liver Index) and LAP (Lipid Accumulation Product), that we will use during the project.

Research paper thumbnail of Changes in Plasma Bioactive Lipids and Inflammatory Markers during a Half-Marathon in Trained Athletes

Applied Sciences, 2021

Background: Exercise may affect lipid profile which in turn is related to inflammation, although ... more Background: Exercise may affect lipid profile which in turn is related to inflammation, although changes of ceramides, diacylglycerols-DAG and sphingomyelin-SM and their relationship with inflammatory parameters following a half-marathon have never been examined. Methods: Ceramides, DAG and SM, and markers of inflammation (soluble fractalkine-CX3CL1, vascular endothelial growth factor-VEGF, interleukin6-IL-6 and tumor necrosis factorα-TNFα) were evaluated in trained half-marathoners before, post-race (withdrawal within 20 min after the race end) and 24 h after. Results: IL-6 and CX3CL1 increased immediately after the race, returning to baseline after 24 h. Total ceramides and total DAG significantly decreased post-race. Several ceramide classes decreased after exercise, while only one of the DAG (36:3) changed significantly. Total SM and specific species did not significantly change. Conclusion: Some inflammatory parameters (IL-6 and CX3CL1) transiently increased after the race, and...

Research paper thumbnail of Biomonitoring of Bis(2-ethylhexyl)phthalate (DEHP) in Italian children and adolescents: Data from LIFE PERSUADED project

Environmental Research, 2020

The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disru... more The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disrupting chemical with main toxicological effects on reproductive and metabolic systems. Human biomonitoring (HBM) studies are promoted to evaluate the background exposure levels. In the frame of LIFE PERSUADED project, the HBM study measured DEHP main metabolites (mono-(2-ethylhexyl) phthalate, MEHP; 2-ethyl-5-hydroxy-hexylphthalate, MEHHP; 2-ethyl-5-oxo-hexylphthalate, MEOHP) in Italian children and adolescent (4-14 years old) according to geographical macro-areas and areas, age and sex. Children from the South and the Centre of Italy showed higher median levels of DEHP, as a sum of its metabolites (48.14 and 47.80 μg/L), than those from the North (39.47 μg/L; p = 0.0090 and 0.0004, respectively). Considering the total population, boys are more exposed than girls (only as urinary volume), and children aged 4-6 years have higher median levels than those 7-10 and 11-14 years old. The derived reference values (RV95) for DEHP in children is 168 μg/L. The relative metabolic rates of DEHP, the background levels and, thus, the RV95, vary with the geographical area, age and sex, indicating that all these parameters should be considered in the risk assessment. leach out of the products and migrate into soils, surface water, sediments, indoor air and foodstuff during processing, packaging and storage phases leading to a widespread human exposure (Pakalin et al., 2008). In 2005, the European Food Safety Authority (EFSA) stated that food contamination is the main source of exposure in the general population and reiterated that DEHP is of concern for its toxicological

Research paper thumbnail of Author Correction: Lack of NLRP3-inflammasome leads to gut-liver axis derangement, gut dysbiosis and a worsened phenotype in a mouse model of NAFLD

Scientific reports, Jan 11, 2017

A correction to this article has been published and is linked from the HTML version of this paper... more A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Research paper thumbnail of Increased hepatic glucose production and insulin resistance are associated to increased plasma concentrations of glucogenic amino acids in subjects with NAFLD

Digestive and Liver Disease, 2017

Research paper thumbnail of Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance

Research paper thumbnail of Lack of NLRP3-inflammasome leads to gut-liver axis derangement and increases hepatic injury in a mouse model of NAFLD

Digestive and Liver Disease, 2016

Research paper thumbnail of Angiopoietin-like4 is associated with lipid metabolism and severe fibrosis in non-diabetic patients with non-alcoholic fatty liver disease

Digestive and Liver Disease, 2016

Research paper thumbnail of The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis

Nutrients, 2015

Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in met... more Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC). The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance. The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance, such as type 2 diabetes and non alcoholic fatty liver disease.

Research paper thumbnail of Peripheral insulin resistance predicts liver damage in nondiabetic subjects with nonalcoholic fatty liver disease

Hepatology, 2015

Surrogate indexes of insulin resistance/sensitivity (IR/IS) are widely used in Non Alcoholic Fatt... more Surrogate indexes of insulin resistance/sensitivity (IR/IS) are widely used in Non Alcoholic Fatty Liver Disease (NAFLD) although they have never been validated in this population. We aimed to validate the available indexes in NAFLD subjects and to test their ability to predict liver damage also in comparison with NAFLD Fibrosis Score (NFS). Surrogate indexes were validated by tracer technique (D2-glucose and U-13C-glucose) in the basal state and during an Oral Glucose Tolerance Test (OGTT). The best performing indexes were used in an independent cohort of 145 non-diabetic NAFLD subjects to identify liver damage (fibrosis and NASH). In the validation NAFLD cohort, HOMA-IR, IGR and ISI Stumvoll had the best association with hepatic IR, while peripheral IS was most significantly related to OGIS, ISI Stumvoll and eMCR(nodem) . In the independent cohort, only OGTT derived indexes were associated with liver damage and OGIS was the best predictor of significant (≥F2) fibrosis (OR=0.76, 95% CI= 0.61-0.96, P=0.0233) and of NASH (OR=0.75, 95% CI=0.63-0.90, P=0.0021). Both OGIS and NFS identified advanced (F3/F4) fibrosis, but OGIS predicted it better than NFS (OR=0.57, 95% CI=0.45-0.72, P<0.001) and was also able to discriminate F2 from F3/F4 (P<0.003). OGIS is associated with peripheral IS in NAFLD and is inversely associated with an increased risk of significant/advanced liver damage in non-diabetic subjects with NAFLD. This article is protected by copyright. All rights reserved.

Research paper thumbnail of P0519 : Lipidomics reveals that low plasma unsaturated to saturated fat ratios are biomarkers of NAFLD and liver damage

Journal of Hepatology, 2015

Research paper thumbnail of O064 : Gut-liver axis derangement due to lack of inflammasome activity leads to visceral obesity and nash development

Journal of Hepatology, 2015

Research paper thumbnail of Liver damage can be associated with deregulation of the de novo lipogenesis pathway in subjects with Non Alcoholic Fatty Liver Disease

Digestive and Liver Disease, 2015

Research paper thumbnail of Validation of surrogate indexes of peripheral and hepatic insulin resistance and evaluation of their utility as non-invasive predictors of histological features in patients with Non-Alcoholic Fatty Liver Disease

Research paper thumbnail of Gut–liver axis derangement due to lack of inflammasome activity leads to visceral obesity and NASH development

Digestive and Liver Disease, 2015

Research paper thumbnail of Ectopic fat: the true culprit linking obesity and cardiovascular disease?

Thrombosis and Haemostasis, 2013

SummaryObesity is a major risk factor for cardiovascular disease and its complications. However, ... more SummaryObesity is a major risk factor for cardiovascular disease and its complications. However, not all fat depots share the same characteristics. Recent studies have found that ectopic rather than subcutaneous fat accumulation is associated with increased cardiometabolic risk. However, ectopic fat accumulation can be seen initially as a protective mechanism against lipotoxicity. Subsequently the adipose tissue becomes dysfunctional, thus inducing systemic metabolic alterations (through release of cytokines) or specific organ dysfunctions. The purpose of this review is to summarise the current available data on the impact of excess adiposity vs ectopic fat in the development of cardiometabolic diseases.

Research paper thumbnail of Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease

Nutrients, 2013

Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse.... more Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs). The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease.

Research paper thumbnail of P849 Quantitative and Qualitative Analysis of Plasma Free Fatty Acids and Their Impact on Liver Damage in Nafld Patients

Journal of Hepatology, 2014

Research paper thumbnail of P843 Alteration in Glucose Metabolism After an Oral Glucose Load and Relationship with Liver Damage in Patients with Nafld

Journal of Hepatology, 2014

P840 ALTERATION IN LIPID METABOLISM AFTER AN ORAL FAT LOAD IN PATIENTS WITH NAFLD L. Mezzabotta, ... more P840 ALTERATION IN LIPID METABOLISM AFTER AN ORAL FAT LOAD IN PATIENTS WITH NAFLD L. Mezzabotta, E. Vanni, C. Rosso, M. Gaggini, R. Gambino, E. Buzzigoli, C. Saponaro, D. Ciociaro, M.L. Abate, F. Saba, F. Salomone, G.P. Caviglia, S. Carenzi, A. Smedile, M. Rizzetto, M. Cassader, A. Gastaldelli, E. Bugianesi. Medical Sciences, University of Turin, Turin, Cardiometabolic Risk Unit, Institute of Clinical Physiology – CNR, Pisa, U.O.C. of Gastroenterology, Azienda Sanitaria Provinciale di Catania, Catania, Italy E-mail: laviniaemme@hotmail.com