Papers by Ornella de Bari
Activation of a novel estrogen receptor GPR30 enhances cholesterol cholelithogenesis in female mice
Hepatology
505 - Activation of G Protein-Coupled Receptor 30 (GPR30), a Novel Estrogen Receptor, by the Potent GPR30-Selective Agonist G-1 Greatly Enhances Cholesterol Cholelithogenesis in Female Mice
Gastroenterology
European journal of clinical investigation, Jan 24, 2018
Physical inactivity puts the populations at risk of several health problems, while regular physic... more Physical inactivity puts the populations at risk of several health problems, while regular physical activity brings beneficial effects on cardiovascular disease, mortality and other health outcomes, including obesity, glycaemic control and insulin resistance. The hepatobiliary tract is greatly involved in several metabolic aspects which include digestion and absorption of nutrients in concert with intestinal motility, bile acid secretion and flow across the enterohepatic circulation, and intestinal microbiota. Several metabolic abnormalities, including non-alcoholic fatty liver as well as cholesterol cholelithiasis represent two conditions explained by changes of the aforementioned pathways. This review defines different training modalities and discusses the effects of physical activity in two metabolic disorders, i.e. non-alcoholic fatty liver disease (NAFLD) and cholelithiasis. Emphasis is given to pathogenic mechanisms involving intestinal bile acids, microbiota and inflammatory ...
Apolipoprotein (apo)A-V Deficiency Enhances Hepatic Synthesis of Ceramide, a Major Fatty Acid Metabolite, Triggering a Progression from Simple Steatosis to Nonalcoholic Steatohepatitis (NASH) in Chow-Fed apoA-V KO Mice
Gastroenterology
The role of dietary approach in irritable bowel syndrome
Current medicinal chemistry, Apr 27, 2017
Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and... more Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most frequent gastrointestinal diseases. In IBS multiple pathophysiological mechanisms including alterations in intestinal motility, permeability, nutrient absorption, and intestinal microbiota have been implicated. Foods are commonly reported by patients to be a trigger of symptoms and therefore are likely involved in the generation of symptoms in IBS. Among all possible therapeutic options, a first-line approach to IBS is dietary education and identification of foods potentially responsible for the onset or worsening of symptoms. Dietary approaches include reduction of gas-producing foods (i.e, fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs)), lactose and gluten. Further studies are required to link the ultimate role of diets in different IBS subtypes.
Modulation of Aquaporins by dietary patterns and plant bioactive compounds
Current medicinal chemistry, May 23, 2017
Healthful dietary patterns and bioactive compounds supplementation can be adopted as simple and e... more Healthful dietary patterns and bioactive compounds supplementation can be adopted as simple and easy intervention to prevent, attenuate or cure clinical disorders, especially when it comes degenerative and chronic diseases. In the recent years, a growing body of evidence indicates Aquaporins (AQPs), a family of membrane channel proteins widely expressed in the human body, among the targets underlying the beneficial action played by some food nutrients and phytochemical compounds. Here, we provide an overview of what is known regarding the AQP modulation exerted by healthful dietary patterns and plant polyphenols.
The Role Of Diet In The Pathogenesis Of Cholesterol Gallstones
Current medicinal chemistry, Jan 29, 2017
Cholesterol gallstone disease is a major health problem in Westernized countries and depends on a... more Cholesterol gallstone disease is a major health problem in Westernized countries and depends on a complex interplay between genetic factors, lifestyle and diet, acting on specific pathogenic mechanisms. Overweigh, obesity, dyslipidemia, insulin resistance and altered cholesterol homeostasis have been linked to increased gallstone occurrence, and several studies point to a number of specific nutrients as risk- or protective factors with respect to gallstone formation in humans, motivating a rising interest in the identification of common and modifiable dietetic factors that put the patients at risk of gallstones or that are able to prevent gallstone formation and growth. In particular, dietary models characterized by increased energy intake with highly refined sugars and sweet foods, high fructose intake, low fiber contents, high fat, consumption of fast food and low vitamin C intake increase the risk of gallstone formation. On the other hand, high intake of monounsaturated fats and ...
Gastroenterology Report, 2017
Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and... more Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most commonly diagnosed gastrointestinal diseases. The impact of IBS on the general population is large due to its high prevalence, suboptimal medical treatments and significant economic burden. The pathophysiology of IBS is complex and treatments are often symptom-specific. The most common therapeutic approaches for IBS include education and reassurance, lifestyles (especially nutrition-based interventions), peripherally acting medications (which typically target motility), centrally acting medications (which target visceral hypersensitivity and pain) and psychological interventions (which aim to reduce the effects of stress or symptom-specific anxiety). A beneficial dietary approach might include the following measures: a diet low in fermentable oligo-,di-and monosaccharides and polyols (FODMAPs), limitation or exclusion of gas-producing foods and/or lactose and gluten and fiber supplementation in selected cases. New therapeutic agents, namely nutraceutics, are also an interesting option in the management of IBS patients. This paper will focus on available dietary interventions for IBS and will review the evidence for nutrition-based therapies.
The deletion of the estrogen receptor α gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice
Biochimica et biophysica acta, Jan 29, 2015
Compelling evidence has demonstrated that estrogen is a critical risk factor for gallstone format... more Compelling evidence has demonstrated that estrogen is a critical risk factor for gallstone formation and enhances cholesterol cholelithogenesis through the hepatic estrogen receptor α (ERα), but not ERβ. To study the lithogenic mechanisms of estrogen through ERα, we investigated whether the deletion of Erα protects against gallstone formation in ovariectomized (OVX) female mice fed a lithogenic diet and treated with 17β-estradiol (E2) at 0 or 6 μg/day for 56 days. Our results showed that the prevalence of gallstones was reduced from 100% in OVX ERα (+/+) mice to 30% in OVX ERα (-/-) mice in response to high doses of E2 and the lithogenic diet for 56 days. Hepatic cholesterol secretion was significantly diminished in OVX ERα (-/-) mice compared to OVX ERα (+/+) mice even fed the lithogenic diet and treated with E2 for 56 days. These alterations decreased bile lithogenicity by reducing cholesterol saturation index of gallbladder bile. Immunohistochemical studies revealed that ERα was ...
Sa1293 GPR30, a Novel Estrogen Receptor, Enhances Cholesterol Cholelithogenesis by Inhibiting Cholesterol 7α-Hydroxylase (CYP7A1) and the Classic Pathway of Bile Acid Synthesis
Gastroenterology, 2013
Sa1336 Molecular Mechanisms Underlying the Critical Role of the G Protein-Coupled Receptor 30 (GPR30), a Novel Estrogen Receptor, in the Formation of Lithogenic Bile Through a Non-Transcriptional Regulatory Mode in 17β-Estradiol (E2)-Treated Mice
Gastroenterology, 2015
Exploring Liver Mitochondrial Function by 13C-Stable Isotope Breath Tests: Implications in Clinical Biochemistry
Methods in Molecular Biology, 2014
The liver plays a pivotal role in a myriad of metabolic processes, including detoxification, glyc... more The liver plays a pivotal role in a myriad of metabolic processes, including detoxification, glycolipidic storage and export, and protein synthesis. Breath tests employing (13)C as stable isotope have been introduced to explore such energy-dependent pathways involving mitochondrial function in the liver. Specific substrates are ketoisocaproic acid, methionine, and octanoic acid. In humans, the application of (13)C-breath tests ranges from nonalcoholic and alcoholic liver diseases to liver cirrhosis, hepatocarcinoma, preoperative and postoperative assessment of liver function, and drug-induced liver damage. Studying liver mitochondrial function by (13)C-breath tests represents a complementary tool to monitor complex metabolic processes in health and disease.
Journal of lipids, 2012
The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concen... more The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1), an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD) in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids ...
Ezetimibe prevents the formation of oestrogen-induced cholesterol gallstones in mice
European journal of clinical investigation, 2014
Oestrogen is an important risk factor for cholesterol cholelithiasis not only in women of childbe... more Oestrogen is an important risk factor for cholesterol cholelithiasis not only in women of childbearing age taking oral contraceptives and postmenopausal women undergoing hormone replacement therapy, but also in male patients receiving oestrogen therapy for prostatic cancer. In women, hormonal changes occurring during pregnancy markedly increase the risk of developing gallstones. We investigated whether the potent cholesterol absorption inhibitor ezetimibe could prevent the formation of oestrogen-induced cholesterol gallstones in mice. Following ovariectomy, female AKR mice were implanted subcutaneously with pellets releasing 17β-estradiol at 6 μg/day and fed a lithogenic diet supplemented with ezetimibe in doses of 0 or 8 mg/kg/day for 8 weeks. Cholesterol crystallization and gallstone prevalence, lipid concentrations and composition in bile, and biliary lipid output were analysed by physical-chemical methods. Intestinal cholesterol absorption efficiency was determined by faecal dua...
Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment
Annals of hepatology
Epidemiological and clinical studies have found that gallstone prevalence is twice as high in wom... more Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations...
38 APOA5 Deficiency Leads to Spontaneous Development of Nonalcoholic Fatty Liver Disease (NAFLD) in Chow-Fed Mice
Gastroenterology, 2014
Role of mitochondria in nonalcoholic fatty liver disease-from origin to propagation
Clinical Biochemistry, 2012
Mitochondria play a major role in cell energy-generating processes and integrate several signalli... more Mitochondria play a major role in cell energy-generating processes and integrate several signalling pathways to control cellular life and death. Several liver diseases are characterized by mitochondrial alterations which are directly or indirectly dependent on the activation of intracellular stress cascades or receptor-mediated pathways. This article examines the role of mitochondrial dysfunction in critical initiating or propagating events in fatty liver infiltration and nonalcoholic fatty liver disease (NAFLD). Genetic variants and the role of drug-induced toxicity have been considered. Key alterations of mitochondrial physiology associated with hepatocyte fatty changes are described. The value of novel non-invasive diagnostic methods to detect mitochondrial metabolic alterations is also discussed. Mitochondrial metabolic remodeling is a predominant factor in the appearance and perpetuation of hepatocyte fat accumulation. Non-invasive techniques to identify mitochondrial dysfunction and proper mitochondria protection are two necessary clinical steps for an efficient management of NAFLD.
World Journal of Gastroenterology, 2013
AIM: To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidat... more AIM: To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes. METHODS: Silybin-phospholipid complex containing vitamin E (Realsil ®) was daily administered by gavage (one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived (CD) or a high fat diet [20% fat, containing 71% total calories as fat, 11% as carbohydrate, and 18% as protein, high fat diet (HFD)] for 30 d and 60 d, respectively. The control group was fed a normal semi-purified diet containing adequate levels of choline (35% total calories as fat, 47% as carbohydrate, and 18% as protein). Circulating and hepatic redox active and nitrogen regulating molecules (thioredoxin, glutathione, glutathione peroxidase), NO metabolites (nitrosothiols, nitrotyrosine), lipid peroxides [malondialdehyde-thiobarbituric (MDA-TBA)], and pro-inflammatory keratins (K-18) were measured on days 0, 7, 14, 30, and 60. Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated. RESULTS: Both diet regimens produced liver steatosis (50% and 25% of liver slices with CD and HFD, respectively) with no signs of necro-inflammation: fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30 (CD) and day 60 (HFD). In plasma, thioredoxin and nitrosothiols were not significantly changed, while MDA-TBA, nitrotyrosine
European Journal of Clinical Investigation, 2013
Background Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interac... more Background Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors and represents a failure of biliary cholesterol homoeostasis in which the physicalchemical balance of cholesterol solubility in bile is disturbed.
Therapeutic Reflections in Cholesterol Homeostasis and Gallstone Disease: A Review
Current Medicinal Chemistry, 2014
Cholesterol gallstone disease is one of the most prevalent and the most costly digestive diseases... more Cholesterol gallstone disease is one of the most prevalent and the most costly digestive diseases in Western countries. Its pathogenesis is a complex paradigm resulting from the interaction of genetic factors, hepatic hypersecretion of cholesterol, increased intestinal absorption of cholesterol, a constantly "supersaturated" bile, crystallization of biliary cholesterol, and gallbladder stasis. De novo cholesterol biosynthesis, biliary cholesterol output, and intestinal cholesterol absorption are therefore key steps involved in cholesterol homeostasis. Establishing the right pharmacological therapy for cholesterol gallstones is of major importance in Western healthcare systems. Certain drugs might independently influence cholesterol gallstone formation by blocking the 3-hydroxy-3-methylglutaryl-coenzyme A reductase and inhibiting cholesterol biosynthesis in the liver (statins) or blocking cholesterol absorption in the small intestine apical membrane by specifically inhibiting the Niemann-Pick C1-like 1 protein (ezetimibe). This review will focus on the possibility that statins and ezetimibe, by acting at different levels of cholesterol homeostasis, might represent novel therapeutic approaches to prevent cholesterol gallstones in selected subjects at risk.
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Papers by Ornella de Bari