Piero Portincasa | University of Bari Italy (original) (raw)

Papers by Piero Portincasa

Research paper thumbnail of Experimental observations and clinical implications of fasting and diet supplementation in fatty livers

PubMed, Aug 12, 2003

Fatty accumulation per se does not appear to affect liver function; however, interest has recentl... more Fatty accumulation per se does not appear to affect liver function; however, interest has recently renewed to fatty liver because of the clinical relevance of non alcoholic steato-hepatitis (NASH) and for the increased risk of post-transplant failure in grafted livers with steatosis. Clinical and experimental studies have doubtless demonstrated that oxidative stress ensues in steatotic livers. Mitochondria represent the preferential target of the oxidative injury associated to fatty degeneration and show reduced content of glutathione, higher levels of oxidative products and damages to enzymes involved in the process of ATP synthesis, which become more evident under stressing conditions. Although obese patients with fatty liver are advantaged by weight loss, clinical and experimental observations suggest that fatty livers poorly tolerate excessive food deprivation. These observations represent the rationale for treatment strategies based on the supplementation of antioxidants and energetic substrates rather than solely a diet restriction. This review focuses on data emerging from a series of investigations performed in rats with fatty livers induced by a choline-deficient diet, which resembles human steatosis due to an excessive intake of carbohydrates, and aims to give the cue for the development of therapeutic options able to preserve hepatic function after transplantation of steatotic organs.

Research paper thumbnail of Targeting mitochondria to oppose the progression of nonalcoholic fatty liver disease

Biochemical Pharmacology, Feb 1, 2019

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulati... more Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue. Mitochondrial dysfunction occurs in NAFLD, and contributes to the progression to the necro-inflammatory and fibrotic form (NASH). Disrupted mitochondrial function is associated with a decrease in the energy levels and impaired redox balance, and negatively affects cell survival by altering overall metabolism and subcellular trafficking. Such events reduce the tolerance of hepatocytes towards damaging hits, and favour the injurious effects of extracellular factors. Here, we discuss the role of mitochondria in NAFLD and focus on potential therapeutic approaches aimed at preserving mitochondrial function.

Research paper thumbnail of 1019 High-Fat Diet Alters the Oligosaccharide Chains of Colon Mucins in Mice

Gastroenterology, May 1, 2014

Research paper thumbnail of Protocols for Mitochondria as the Target of Pharmacological Therapy in the Context of Nonalcoholic Fatty Liver Disease (NAFLD)

Methods in molecular biology, 2021

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent metabolic chronic liver dise... more Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent metabolic chronic liver diseases in developed countries and puts the populations at risk of progression to liver necro inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Mitochondrial dysfunction is involved in the onset of NAFLD and contributes to the progression from NAFLD to nonalcoholic steatohepatitis (NASH). Thus, liver mitochondria could become the target for treatments for improving liver function in NAFLD patients. This chapter describes the most important steps used for potential therapeutic interventions in NAFLD patients, discusses current options gathered from both experimental and clinical evidence, and presents some novel options for potentially improving mitochondrial function in NAFLD.

Research paper thumbnail of (13C)-Methacetin breath test provides evidence of subclinical liver dysfunction linked to fat storage but not lifestyle

JHEP reports, Feb 1, 2021

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of ... more Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation, and is usually associated with visceral, metabolically active obesity. However, the subclinical effects of body and liver fat accumulation on liver function are still unclear. Methods: We used orally administered (13 C)-methacetin and breath test to quantify the efficiency of hepatic extraction from portal blood flow and liver microsomal function in 81 participants, in relation to presence/absence of ultrasonographic NAFLD, extent of body fat accumulation, insulin resistance, dietary models, and lifestyle. Results: NAFLD was present in 23% of participants with normal weight, and prevalence increased with body fat and insulin resistance. Fat accumulation, NAFLD, and insulin resistance were associated with decreased hepatic extraction efficiency, and liver microsomal function was impaired in moderate-to-severe NAFLD. Caloric intake, dietary models, and lifestyles had a minor role in promoting functional changes. Conclusions: The interplay between body fat accumulation, insulin resistance, and NAFLD is linked with altered hepatic extraction efficiency from blood flow and deranged microsomal function. Non-invasive diagnosis of subclinical alterations of liver function is relevant for primary and secondary prevention measures. Furthermore, the occurrence of NAFLD in lean individuals and the evidence that caloric intake, dietary models, and lifestyle played a minor role require further studies exploring the role of environmental factors in the natural history of these diseases.

Research paper thumbnail of F-19 The silybin-phospholipids complex counteracts fatty degeneration, nitrosative and oxidative stress in two rodent models of liver steatosis

Digestive and Liver Disease, Feb 1, 2012

Research paper thumbnail of Mo1989 A Multicenter Study for Noninvasive Characterization of Metabolic Liver Steatosis/Steatohepatitis

Gastroenterology, May 1, 2014

Research paper thumbnail of The silybin-phospholipids complex counteract fatty de generation, nitro sative and oxidative stress in two rodent models of liver steatosis

Research paper thumbnail of Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome

Pediatric Gastroenterology, Hepatology & Nutrition, 2020

The metabolic syndrome, by definition, is not a disease but is a clustering of individual metabol... more The metabolic syndrome, by definition, is not a disease but is a clustering of individual metabolic risk factors including abdominal obesity, hyperglycemia, hypertriglyceridemia, hypertension, and low high-density lipoprotein cholesterol levels. These risk factors could dramatically increase the prevalence of type 2 diabetes and cardiovascular disease. The reported prevalence of the metabolic syndrome varies, greatly depending on the definition used, gender, age, socioeconomic status, and the ethnic background of study cohorts. Clinical and epidemiological studies have clearly demonstrated that the metabolic syndrome starts with central obesity. Because the prevalence of obesity has doubly increased worldwide over the past 30 years, the prevalence of the metabolic syndrome has markedly boosted in parallel. Therefore, obesity has been recognized as the leading cause for the metabolic syndrome since it is strongly associated with all metabolic risk factors. High prevalence of the metabolic syndrome is not unique to the USA and Europe and it is also increasing in most Asian countries. Insulin resistance has elucidated most, if not all, of the pathophysiology of the metabolic syndrome because it contributes to hyperglycemia. Furthermore, a major contributor to the development of insulin resistance is an overabundance of circulating fatty acids. Plasma fatty acids are derived mainly from the triglycerides stored in adipose tissues, which are released through the action of the cyclic AMP-dependent enzyme, hormone sensitive lipase. This review summarizes the latest concepts in the definition, pathogenesis, pathophysiology, and diagnosis of the metabolic syndrome, as well as its preventive measures and therapeutic strategies in children and adolescents.

Research paper thumbnail of New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation

Biochimica Et Biophysica Acta - Molecular And Cell Biology Of Lipids, Nov 1, 2009

Epidemiological and clinical studies have found that at all ages women are twice as likely as men... more Epidemiological and clinical studies have found that at all ages women are twice as likely as men to form cholesterol gallstones, and this gender difference begins since puberty and continues through the childbearing years, which highlight the importance of female sex hormones. Estrogen is a crucial hormone in human physiology and regulates a multitude of biological processes. The actions of estrogen have traditionally been ascribed to two closely related classical nuclear hormone receptors, estrogen receptor 1 (ESR1) and ESR2. Recent studies have revealed that the increased risk for cholesterol gallstones in women vs. men is related to differences in how the liver metabolizes cholesterol in response to estrogen. A large number of human and animal studies have proposed that estrogen increases the risk of developing cholesterol gallstones by increasing the hepatic secretion of biliary cholesterol, which, in turn, leads to an increase in cholesterol saturation of bile. Furthermore, it has been identified that hepatic ESR1, but not ESR2, plays a major role in cholesterol gallstone formation in mice in response to high doses of 17β-estradiol. The mechanisms mediating estrogen's action has become more complicated with the recent identification of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), a member of the seven-transmembrane G proteincoupled receptor superfamily. In this review, we provide an overview of the evidence for the lithogenic actions of estrogen through ESR1 and discuss the cellular and physiological actions of GPR30 in estrogen-dependent processes and the relationship between GPR30 and classical ESR1 on gallstone formation.

Research paper thumbnail of Overcoming Ductal Block: Emergency ERCP and Sphincterotomy Plus Common Bile Duct Stenting Improves Therapeutic Outcomes in Severe Gallstone Pancreatitis

Digestive Diseases and Sciences, 2021

Research paper thumbnail of Bile duct ligation and early biochemical damage of the liver. An experimental model in the rat

European Journal of Clinical Investigation, 2010

Research paper thumbnail of An innovative methodology for the automated morphometric and quantitative estimation of liver steatosis

Histology and histopathology, 2009

The management of liver steatosis, due to its potential evolution towards severe diseases, requir... more The management of liver steatosis, due to its potential evolution towards severe diseases, requires accurate diagnosis. Fatty infiltration in liver diseases is commonly assessed histologically by semi-quantitative methods, which can be subjective. Automated computerized procedures using commercial software for image analysis have also been recently employed. The aim of the study was to develop an innovative automated computerized procedure to accurately evaluate both the morphometry and degree of lipid accumulation in liver. Fatty infiltration was assessed in paraffin- and resin-embedded samples of steatotic livers from rats undergoing 0, 3, 7, 14, and 30-day choline-deficient diet, and from liver biopsy of a morbidly obese patient undergoing bariatric surgery. Specific software was developed, which works with a morphological operator, in addition to a chromatic one to select lipid droplets. The choline-deficient diet induced steatosis with a gradual shift from micro- to macro-vesic...

Research paper thumbnail of Novel insights in health-promoting properties of sweet cherries

Journal of Functional Foods, 2020

Sweet cherry (Prunus avium L.) is one of the most popular and appreciated temperate fruit not onl... more Sweet cherry (Prunus avium L.) is one of the most popular and appreciated temperate fruit not only for its sensory and nutritional properties, but also for its content in bioactive compounds. Consumption of sweet cherries brings beneficial effects on to health, which include prevention and modulatory effects in several chronic diseases such as (diabetes mellitus, cancer, cardiovascular and other inflammatory diseases). The presence of natural polyphenolic compounds with high antioxidant potential might drive and partly explain such beneficial effects, but more translational and clinical studies should address this topic. Here, we review the health-promoting properties of cherries and their bioactive compounds against human diseases. 1. Introduction Sweet cherry (Prunus avium L.

Research paper thumbnail of Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria

International Journal of Molecular Sciences, 2019

Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. H... more Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. However, how the crosstalk between visceral and ectopic fat depots occurs and which are the determinants of ectopic fat expansion and dysfunction remains unknown. Here, we focused on the impact of gender in the crosstalk between visceral and epicardial fat depots and the role of adipocytokines and high-sensitivity C-reactive protein (hs-CRP). A total of 141 outward patients (both men and women) with one or more defining criteria for metabolic syndrome (MetS) were consecutively enrolled. For all patients, demographic and clinical data were collected and ultrasound assessment of visceral adipose tissue (VFth) and epicardial fat (EFth) thickness was performed. Hs-CRP and adipocytokine levels were assessed by enzyme-linked immunosorbent assay (ELISA). Men were characterized by increased VFth and EFth (p-value < 0.001 and 0.014, respectively), whereas women showed higher levels of adiponect...

Research paper thumbnail of Aging and nutrition. Paving the way to better health

Romanian Journal of Internal Medicine, 2020

Sufficient caloric intake is important to maintain the balanced health status, especially during ... more Sufficient caloric intake is important to maintain the balanced health status, especially during the period of aging, as aging and sickness share paths. Maintaining adequate nutritional balance is the best preventive measure to counteract the risk of malnutrition. There are several causes for malnutrition in elderly people, and some techniques such as anthropometric measurements, laboratory and clinical parameters could help to diagnose malnutrition in these patients. The use of a simple validated questionnaire called the ‘Mini Nutritional Assessment’ measures the nutritional status of elderly patients. In this review, we discuss about the malnutrition in elderly people with and without a known cause and we present some of nutritional intervention. There are promising strategies that help overcoming malnutrition.

Research paper thumbnail of Aquaporins as Targets of Dietary Bioactive Phytocompounds

Frontiers in molecular biosciences, 2018

Plant-derived bioactive compounds have protective role for plants but may also modulate several p... more Plant-derived bioactive compounds have protective role for plants but may also modulate several physiological processes of plant consumers. In the last years, a wide spectrum of phytochemicals have been found to be beneficial to health interacting with molecular signaling pathways underlying critical functions such as cell growth and differentiation, apoptosis, autophagy, inflammation, redox balance, cell volume regulation, metabolic homeostasis, and energy balance. Hence, a large number of biologically active phytocompounds of foods have been isolated, characterized, and eventually modified representing a natural source of novel molecules to prevent, delay or cure several human diseases. Aquaporins (AQPs), a family of membrane channel proteins involved in many body functions, are emerging among the targets of bioactive phytochemicals in imparting their beneficial actions. Here, we provide a comprehensive review of this fast growing topic focusing especially on what it is known on t...

Research paper thumbnail of Mouse models of gallstone disease

Current opinion in gastroenterology, 2018

The establishment of mouse models of gallstones, and the contribution of mouse models to genetic ... more The establishment of mouse models of gallstones, and the contribution of mouse models to genetic studies of gallstone disease, as well as the latest advances in the pathophysiology of gallstones from mouse experiments are summarized. The combined uses of genomic strategies and phenotypic studies in mice have successfully led to the identification of many Lith genes, which pave the way for the discovery of human LITH genes. The physical-chemical, genetic, and molecular biological studies of gallstone disease in mice with knockout or transgene of specific target genes have provided many novel insights into the complex pathophysiological mechanisms of this very common hepatobiliary disease worldwide, showing that interactions of five primary defects play a critical role in the pathogenesis of cholesterol gallstones. Based on mouse studies, a new concept has been proposed that hepatic hypersecretion of biliary cholesterol is induced by multiple Lith genes, with insulin resistance as par...

Research paper thumbnail of Transintestinal cholesterol excretion (TICE): A secondary, non-biliary pathway contributing to reverse cholesterol transport

Hepatology (Baltimore, Md.), Oct 27, 2017

publication late 2017), supports this approach to management. Colombo et al. demonstrated that so... more publication late 2017), supports this approach to management. Colombo et al. demonstrated that sofosbuvir-ledipasvir is safe and extremely effective at eradicating HCV in KT recipients with genotype 1 and 4 infection. (1) The results of this trial will certainly impact the care of KT recipients with HCV infection and hopefully clear the way for increased use of HCV-positive kidneys for transplantation into HCV-infected dialysis patients.

Research paper thumbnail of Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice

Scientific Reports, 2015

Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue... more Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity and hepatosteatosis of ob/ob mice and to a down-regulation of AQP...

Research paper thumbnail of Experimental observations and clinical implications of fasting and diet supplementation in fatty livers

PubMed, Aug 12, 2003

Fatty accumulation per se does not appear to affect liver function; however, interest has recentl... more Fatty accumulation per se does not appear to affect liver function; however, interest has recently renewed to fatty liver because of the clinical relevance of non alcoholic steato-hepatitis (NASH) and for the increased risk of post-transplant failure in grafted livers with steatosis. Clinical and experimental studies have doubtless demonstrated that oxidative stress ensues in steatotic livers. Mitochondria represent the preferential target of the oxidative injury associated to fatty degeneration and show reduced content of glutathione, higher levels of oxidative products and damages to enzymes involved in the process of ATP synthesis, which become more evident under stressing conditions. Although obese patients with fatty liver are advantaged by weight loss, clinical and experimental observations suggest that fatty livers poorly tolerate excessive food deprivation. These observations represent the rationale for treatment strategies based on the supplementation of antioxidants and energetic substrates rather than solely a diet restriction. This review focuses on data emerging from a series of investigations performed in rats with fatty livers induced by a choline-deficient diet, which resembles human steatosis due to an excessive intake of carbohydrates, and aims to give the cue for the development of therapeutic options able to preserve hepatic function after transplantation of steatotic organs.

Research paper thumbnail of Targeting mitochondria to oppose the progression of nonalcoholic fatty liver disease

Biochemical Pharmacology, Feb 1, 2019

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulati... more Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue. Mitochondrial dysfunction occurs in NAFLD, and contributes to the progression to the necro-inflammatory and fibrotic form (NASH). Disrupted mitochondrial function is associated with a decrease in the energy levels and impaired redox balance, and negatively affects cell survival by altering overall metabolism and subcellular trafficking. Such events reduce the tolerance of hepatocytes towards damaging hits, and favour the injurious effects of extracellular factors. Here, we discuss the role of mitochondria in NAFLD and focus on potential therapeutic approaches aimed at preserving mitochondrial function.

Research paper thumbnail of 1019 High-Fat Diet Alters the Oligosaccharide Chains of Colon Mucins in Mice

Gastroenterology, May 1, 2014

Research paper thumbnail of Protocols for Mitochondria as the Target of Pharmacological Therapy in the Context of Nonalcoholic Fatty Liver Disease (NAFLD)

Methods in molecular biology, 2021

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent metabolic chronic liver dise... more Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent metabolic chronic liver diseases in developed countries and puts the populations at risk of progression to liver necro inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Mitochondrial dysfunction is involved in the onset of NAFLD and contributes to the progression from NAFLD to nonalcoholic steatohepatitis (NASH). Thus, liver mitochondria could become the target for treatments for improving liver function in NAFLD patients. This chapter describes the most important steps used for potential therapeutic interventions in NAFLD patients, discusses current options gathered from both experimental and clinical evidence, and presents some novel options for potentially improving mitochondrial function in NAFLD.

Research paper thumbnail of (13C)-Methacetin breath test provides evidence of subclinical liver dysfunction linked to fat storage but not lifestyle

JHEP reports, Feb 1, 2021

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of ... more Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation, and is usually associated with visceral, metabolically active obesity. However, the subclinical effects of body and liver fat accumulation on liver function are still unclear. Methods: We used orally administered (13 C)-methacetin and breath test to quantify the efficiency of hepatic extraction from portal blood flow and liver microsomal function in 81 participants, in relation to presence/absence of ultrasonographic NAFLD, extent of body fat accumulation, insulin resistance, dietary models, and lifestyle. Results: NAFLD was present in 23% of participants with normal weight, and prevalence increased with body fat and insulin resistance. Fat accumulation, NAFLD, and insulin resistance were associated with decreased hepatic extraction efficiency, and liver microsomal function was impaired in moderate-to-severe NAFLD. Caloric intake, dietary models, and lifestyles had a minor role in promoting functional changes. Conclusions: The interplay between body fat accumulation, insulin resistance, and NAFLD is linked with altered hepatic extraction efficiency from blood flow and deranged microsomal function. Non-invasive diagnosis of subclinical alterations of liver function is relevant for primary and secondary prevention measures. Furthermore, the occurrence of NAFLD in lean individuals and the evidence that caloric intake, dietary models, and lifestyle played a minor role require further studies exploring the role of environmental factors in the natural history of these diseases.

Research paper thumbnail of F-19 The silybin-phospholipids complex counteracts fatty degeneration, nitrosative and oxidative stress in two rodent models of liver steatosis

Digestive and Liver Disease, Feb 1, 2012

Research paper thumbnail of Mo1989 A Multicenter Study for Noninvasive Characterization of Metabolic Liver Steatosis/Steatohepatitis

Gastroenterology, May 1, 2014

Research paper thumbnail of The silybin-phospholipids complex counteract fatty de generation, nitro sative and oxidative stress in two rodent models of liver steatosis

Research paper thumbnail of Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome

Pediatric Gastroenterology, Hepatology & Nutrition, 2020

The metabolic syndrome, by definition, is not a disease but is a clustering of individual metabol... more The metabolic syndrome, by definition, is not a disease but is a clustering of individual metabolic risk factors including abdominal obesity, hyperglycemia, hypertriglyceridemia, hypertension, and low high-density lipoprotein cholesterol levels. These risk factors could dramatically increase the prevalence of type 2 diabetes and cardiovascular disease. The reported prevalence of the metabolic syndrome varies, greatly depending on the definition used, gender, age, socioeconomic status, and the ethnic background of study cohorts. Clinical and epidemiological studies have clearly demonstrated that the metabolic syndrome starts with central obesity. Because the prevalence of obesity has doubly increased worldwide over the past 30 years, the prevalence of the metabolic syndrome has markedly boosted in parallel. Therefore, obesity has been recognized as the leading cause for the metabolic syndrome since it is strongly associated with all metabolic risk factors. High prevalence of the metabolic syndrome is not unique to the USA and Europe and it is also increasing in most Asian countries. Insulin resistance has elucidated most, if not all, of the pathophysiology of the metabolic syndrome because it contributes to hyperglycemia. Furthermore, a major contributor to the development of insulin resistance is an overabundance of circulating fatty acids. Plasma fatty acids are derived mainly from the triglycerides stored in adipose tissues, which are released through the action of the cyclic AMP-dependent enzyme, hormone sensitive lipase. This review summarizes the latest concepts in the definition, pathogenesis, pathophysiology, and diagnosis of the metabolic syndrome, as well as its preventive measures and therapeutic strategies in children and adolescents.

Research paper thumbnail of New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation

Biochimica Et Biophysica Acta - Molecular And Cell Biology Of Lipids, Nov 1, 2009

Epidemiological and clinical studies have found that at all ages women are twice as likely as men... more Epidemiological and clinical studies have found that at all ages women are twice as likely as men to form cholesterol gallstones, and this gender difference begins since puberty and continues through the childbearing years, which highlight the importance of female sex hormones. Estrogen is a crucial hormone in human physiology and regulates a multitude of biological processes. The actions of estrogen have traditionally been ascribed to two closely related classical nuclear hormone receptors, estrogen receptor 1 (ESR1) and ESR2. Recent studies have revealed that the increased risk for cholesterol gallstones in women vs. men is related to differences in how the liver metabolizes cholesterol in response to estrogen. A large number of human and animal studies have proposed that estrogen increases the risk of developing cholesterol gallstones by increasing the hepatic secretion of biliary cholesterol, which, in turn, leads to an increase in cholesterol saturation of bile. Furthermore, it has been identified that hepatic ESR1, but not ESR2, plays a major role in cholesterol gallstone formation in mice in response to high doses of 17β-estradiol. The mechanisms mediating estrogen's action has become more complicated with the recent identification of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), a member of the seven-transmembrane G proteincoupled receptor superfamily. In this review, we provide an overview of the evidence for the lithogenic actions of estrogen through ESR1 and discuss the cellular and physiological actions of GPR30 in estrogen-dependent processes and the relationship between GPR30 and classical ESR1 on gallstone formation.

Research paper thumbnail of Overcoming Ductal Block: Emergency ERCP and Sphincterotomy Plus Common Bile Duct Stenting Improves Therapeutic Outcomes in Severe Gallstone Pancreatitis

Digestive Diseases and Sciences, 2021

Research paper thumbnail of Bile duct ligation and early biochemical damage of the liver. An experimental model in the rat

European Journal of Clinical Investigation, 2010

Research paper thumbnail of An innovative methodology for the automated morphometric and quantitative estimation of liver steatosis

Histology and histopathology, 2009

The management of liver steatosis, due to its potential evolution towards severe diseases, requir... more The management of liver steatosis, due to its potential evolution towards severe diseases, requires accurate diagnosis. Fatty infiltration in liver diseases is commonly assessed histologically by semi-quantitative methods, which can be subjective. Automated computerized procedures using commercial software for image analysis have also been recently employed. The aim of the study was to develop an innovative automated computerized procedure to accurately evaluate both the morphometry and degree of lipid accumulation in liver. Fatty infiltration was assessed in paraffin- and resin-embedded samples of steatotic livers from rats undergoing 0, 3, 7, 14, and 30-day choline-deficient diet, and from liver biopsy of a morbidly obese patient undergoing bariatric surgery. Specific software was developed, which works with a morphological operator, in addition to a chromatic one to select lipid droplets. The choline-deficient diet induced steatosis with a gradual shift from micro- to macro-vesic...

Research paper thumbnail of Novel insights in health-promoting properties of sweet cherries

Journal of Functional Foods, 2020

Sweet cherry (Prunus avium L.) is one of the most popular and appreciated temperate fruit not onl... more Sweet cherry (Prunus avium L.) is one of the most popular and appreciated temperate fruit not only for its sensory and nutritional properties, but also for its content in bioactive compounds. Consumption of sweet cherries brings beneficial effects on to health, which include prevention and modulatory effects in several chronic diseases such as (diabetes mellitus, cancer, cardiovascular and other inflammatory diseases). The presence of natural polyphenolic compounds with high antioxidant potential might drive and partly explain such beneficial effects, but more translational and clinical studies should address this topic. Here, we review the health-promoting properties of cherries and their bioactive compounds against human diseases. 1. Introduction Sweet cherry (Prunus avium L.

Research paper thumbnail of Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria

International Journal of Molecular Sciences, 2019

Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. H... more Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. However, how the crosstalk between visceral and ectopic fat depots occurs and which are the determinants of ectopic fat expansion and dysfunction remains unknown. Here, we focused on the impact of gender in the crosstalk between visceral and epicardial fat depots and the role of adipocytokines and high-sensitivity C-reactive protein (hs-CRP). A total of 141 outward patients (both men and women) with one or more defining criteria for metabolic syndrome (MetS) were consecutively enrolled. For all patients, demographic and clinical data were collected and ultrasound assessment of visceral adipose tissue (VFth) and epicardial fat (EFth) thickness was performed. Hs-CRP and adipocytokine levels were assessed by enzyme-linked immunosorbent assay (ELISA). Men were characterized by increased VFth and EFth (p-value < 0.001 and 0.014, respectively), whereas women showed higher levels of adiponect...

Research paper thumbnail of Aging and nutrition. Paving the way to better health

Romanian Journal of Internal Medicine, 2020

Sufficient caloric intake is important to maintain the balanced health status, especially during ... more Sufficient caloric intake is important to maintain the balanced health status, especially during the period of aging, as aging and sickness share paths. Maintaining adequate nutritional balance is the best preventive measure to counteract the risk of malnutrition. There are several causes for malnutrition in elderly people, and some techniques such as anthropometric measurements, laboratory and clinical parameters could help to diagnose malnutrition in these patients. The use of a simple validated questionnaire called the ‘Mini Nutritional Assessment’ measures the nutritional status of elderly patients. In this review, we discuss about the malnutrition in elderly people with and without a known cause and we present some of nutritional intervention. There are promising strategies that help overcoming malnutrition.

Research paper thumbnail of Aquaporins as Targets of Dietary Bioactive Phytocompounds

Frontiers in molecular biosciences, 2018

Plant-derived bioactive compounds have protective role for plants but may also modulate several p... more Plant-derived bioactive compounds have protective role for plants but may also modulate several physiological processes of plant consumers. In the last years, a wide spectrum of phytochemicals have been found to be beneficial to health interacting with molecular signaling pathways underlying critical functions such as cell growth and differentiation, apoptosis, autophagy, inflammation, redox balance, cell volume regulation, metabolic homeostasis, and energy balance. Hence, a large number of biologically active phytocompounds of foods have been isolated, characterized, and eventually modified representing a natural source of novel molecules to prevent, delay or cure several human diseases. Aquaporins (AQPs), a family of membrane channel proteins involved in many body functions, are emerging among the targets of bioactive phytochemicals in imparting their beneficial actions. Here, we provide a comprehensive review of this fast growing topic focusing especially on what it is known on t...

Research paper thumbnail of Mouse models of gallstone disease

Current opinion in gastroenterology, 2018

The establishment of mouse models of gallstones, and the contribution of mouse models to genetic ... more The establishment of mouse models of gallstones, and the contribution of mouse models to genetic studies of gallstone disease, as well as the latest advances in the pathophysiology of gallstones from mouse experiments are summarized. The combined uses of genomic strategies and phenotypic studies in mice have successfully led to the identification of many Lith genes, which pave the way for the discovery of human LITH genes. The physical-chemical, genetic, and molecular biological studies of gallstone disease in mice with knockout or transgene of specific target genes have provided many novel insights into the complex pathophysiological mechanisms of this very common hepatobiliary disease worldwide, showing that interactions of five primary defects play a critical role in the pathogenesis of cholesterol gallstones. Based on mouse studies, a new concept has been proposed that hepatic hypersecretion of biliary cholesterol is induced by multiple Lith genes, with insulin resistance as par...

Research paper thumbnail of Transintestinal cholesterol excretion (TICE): A secondary, non-biliary pathway contributing to reverse cholesterol transport

Hepatology (Baltimore, Md.), Oct 27, 2017

publication late 2017), supports this approach to management. Colombo et al. demonstrated that so... more publication late 2017), supports this approach to management. Colombo et al. demonstrated that sofosbuvir-ledipasvir is safe and extremely effective at eradicating HCV in KT recipients with genotype 1 and 4 infection. (1) The results of this trial will certainly impact the care of KT recipients with HCV infection and hopefully clear the way for increased use of HCV-positive kidneys for transplantation into HCV-infected dialysis patients.

Research paper thumbnail of Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice

Scientific Reports, 2015

Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue... more Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity and hepatosteatosis of ob/ob mice and to a down-regulation of AQP...