Browsing by Author "Nervi Oddone, Flavio"
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- ItemDiet as a risk factor for cholesterol gallstone disease(2004) Cuevas Marín, Ada Marisa; Miquel Poblete, Juan Francisco; Reyes Soto, María Soledad; Zanlungo Matsuhiro, Silvana; Nervi Oddone, FlavioCholesterol gallstone disease is a common condition in western populations. The etiology is multifactorial with interaction of genetic and environmental factors. Obesity, aging, estrogen treatment, pregnancy and diabetes are consistently associated to a higher risk. A number of dietary factors have been involved in the pathogenesis of cholelithiasis. In this article we summarize several studies that have evaluated the role of diet as a potential risk factor for gallstone formation, including energy intake, cholesterol, fatty acids, fiber, carbohydrates, vitamins and minerals, and alcohol intake. Consumption of simple sugars and saturated fat has been mostly associated to a higher risk, while fiber intake and moderate consumption of alcohol, consistently reduce the risk. The association between cholesterol intake and gallstone disease has been variable in different studies. The effects of other dietary factors are less conclusive; additional studies are therefore necessary to clarify their relevance in the pathogenesis of gallstone disease. Recent discoveries of the role of orphan nuclear receptors in the regulation of fatty acid and hepatic cholesterol metabolism and excretion open new perspectives for a better understanding of the role of dietary constituents on cholesterol gallstone formation. KEY TEACHING POINTS: The etiology of cholesterol gallstone disease is multifactorial with interaction between genome and environment. It has been postulated that dietary constituents are important determinants for the formation of lithogenic bile. Intake of high energy, simple sugar and saturated fat favors gallstone formation. Fiber and moderate consumption of alcohol reduce the risk. The role of orphan nuclear receptors in the regulation of hepatic cholesterol metabolism and excretion open new leads for understanding the role of dietary constituents on cholesterol gallstone formation.
- ItemHepatic cholesterol transport from plasma into bile: implications for gallstone disease(2004) Zanlungo Matsuhiro, Silvana; Rigotti Rivera, Attilio Gianpietro; Nervi Oddone, FlavioPurpose of reviewThe transhepatic traffic of cholesterol from plasma lipoproteins into the bile is critical for overall cholesterol homeostasis and its alterations may lead to cholesterol gallstone formation. This review summarizes recent progress in understanding the key hepatic cholesterol metabolism-related proteins and pathways that influence biliary secretion of cholesterol.Recent findingsIn cholesterol-fed apolipoprotein E knockout mice, the availability of dietary cholesterol for biliary disposal is decreased and diet-induced gallstone formation is impaired. Scavenger receptor class B type I is relevant for cholesterol transport from plasma HDL into the bile in chow-fed mice, however its expression is not critical for biliary cholesterol secretion and gallstone formation in lithogenic diet-fed mice. Intrahepatic cholesterol transport proteins (e.g. sterol carrier protein-2, Niemann Pick type C-1 protein) also determine liver cholesterol available for biliary secretion in mice. Genetic manipulation of canalicular ATP-binding cassette transporter G5 and G8 expression in mice has established their essential role for biliary cholesterol secretion.SummaryRecent studies have underscored that different proteins involved in hepatic cholesterol transport regulate the availability of cholesterol for biliary secretion. These advances may provide new avenues for prevention and treatment of various disease conditions linked to abnormal cholesterol metabolism.
- ItemHypoadiponectinemia and its Association with Liver Fibrosis in Morbidly Obese Patients(2010) Nazal Ortiz, Leyla María; Riquelme Pérez, Arnoldo Javier; Solís López, Nancy De Las Mercedes; Pizarro Rojas, Margarita Alicia; Escalona Pérez, Alex Gamaliel; Burotto Pichun, Mauricio Emanuel; Méndez, Juan Ignacio; Saint-Jean, Catalina; Concha Bustos, María José; Giovanni, Stefano; Awruch Diego Ariel; Morales Soto, Arturo Javier; Baudrand Biggs, Rene Felipe; Carrasco Avino, Gonzalo; Domínguez De Landa, María Angelica; Padilla Pérez, Oslando; Espinoza, Manuel; Miquel, Juan Francisco; Nervi Oddone, Flavio; Arrese Jiménez, Marco AntonioReduced serum levels of adiponectin have been associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD). However, the relationship between serum adiponectin levels and hepatic histology in NAFLD is controversial. The aim of this study was to explore associations between plasma adiponectin concentrations and liver histology in morbidly obese patients.", "We conducted a case-control study including obese patients undergoing bariatric surgery and normal controls. Anthropometric, standard biochemical variables as well as plasma adiponectin and leptin levels were determined. Liver biopsy was performed in all patients at the time of surgery.", "Seventy morbidly obese patients (mean BMI, 40.6 +/- 5.6 kg/m(2)) met the inclusion criteria and were compared with 69 controls (mean BMI, 22.8 +/- 1.6 kg/m(2), p = 0.0001). Thirty patients (43%) had NAFLD and 20 (28%) of them fulfilled the histological criteria for steatohepatitis. Obesity was associated with increased leptin and decreased adiponectin levels. NAFLD patients exhibited decreased levels of serum adiponectin compared with matched controls [median (Q1-Q3), 3.9 (3.2-4.3) vs. 8.6 (6.5-9.2) mu g/mL, p < 0.0001]. In univariate analysis, age, gender, type 2 diabetes mellitus, BMI, HOMA-IR, aspartate aminotransferase (AST), alanine aminotransferase, serum glucose, and adiponectin levels were independently associated with hepatic fibrosis. In multivariate analysis, AST [OR = 1.082 (1.000-1.170)], age [OR = 1.119 (1.023-1.225)], and serum adiponectin levels [OR = 0.529 (0.299-0.936)] were significantly associated with the presence of liver fibrosis.", "NAFLD patients have lower plasma adiponectin concentrations than control subjects. Low adiponectin levels are associated with more severe liver histology. Serum adiponectin may be useful to estimate the severity of liver damage in obese patients with NAFLD.
- ItemImpaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet(2000) Amigo Boker, Ludwig Peter; Quiñones, Verónica; Mardones, Pablo; Zanlungo Matsuhiro, Silvana; Miquel Poblete, Juan Francisco; Nervi Oddone, Flavio; Rigotti Rivera, Attilio GianpietroBackground & aimsBecause apolipoprotein E (apoE) is a key cholesterol transport molecule involved in the hepatic uptake of chylomicron cholesterol, it may play a critical role in controlling bile cholesterol elimination and cholesterol gallstone formation induced by dietary cholesterol. To test this hypothesis, we studied biliary lipid secretion and gallstone formation in apoE-deficient mice fed cholesterol-rich diets.MethodsBile lipid outputs and gallstone sequence events were analyzed in apoE-deficient mice fed a high-cholesterol diet or a lithogenic diet compared with control animals.ResultsA high-cholesterol diet increased biliary cholesterol secretion and gallbladder bile cholesterol concentration in wild-type mice; the increase in bile cholesterol secretion was significantly attenuated in apoE-deficient mice. ApoE knockout mice fed a high-cholesterol lithogenic diet had a markedly lower frequency of gallbladder bile cholesterol crystal and gallstone formation than wild-type mice, which was most likely a result of the decreased cholesterol saturation index found in gallbladder bile of apoE-deficient mice.ConclusionsThese results show that apoE expression is an important factor for regulating both biliary secretion of diet-derived cholesterol as well as diet-induced cholesterol gallstone formation in mice.
- ItemThe ABCs of biliary cholesterol secretion and their implication for gallstone disease(2003) Zanlungo Matsuhiro, Silvana; Miquel Poblete, Juan Francisco; Rigotti Rivera, Attilio Gianpietro; Nervi Oddone, Flavio
- ItemThe ACAT2 gene encodes a gatekeeper of intestinal cholesterol absorption that regulates cholesterolemia and gallstone disease(2001) Zanlungo Matsuhiro, Silvana; Nervi Oddone, Flavio
- ItemThe molecular and metabolic basis of biliary cholesterol secretion and gallstone disease(2003) Zanlungo Matsuhiro, Silvana; Nervi Oddone, FlavioThis article presents an up to date of selected aspects of the molecular mechanisms of cholesterol metabolism most likely involved in cholesterol gallstones disease, a highly prevalent disease in the Western world. The etiology of cholesterol cholelithiasis is considered to be multifactorial, with interaction of genetic and environmental factors. The production of supersaturated bile by the liver of cholesterol is a key early metabolic event underlying cholesterol lithogenesis. Regulation of hepatic cholesterol trafficking within the hepatocyte appears essential for the production of cholesterol supersaturated bile. Impaired sorting of metabolically active hepatic free cholesterol to the bile acid biosynthetic or lipoprotein production pathways leads to an increased availability of cholesterol for preferential channeling of cholesterol to the canalicular membrane and further secretion into bile. Many of these intrahepatic cholesterol trafficking steps are under genetic control and might be influenced by a variety of environmental factors. This review summarizes recent discoveries related to transhepatic cholesterol flux and biliary lipid secretion, which have provided new insights to the regulation of hepatic cholesterol metabolism as related to gallstone disease.
- ItemThe old enigma of diets, oils, and stones(2005) Miquel Poblete, Juan Francisco; Zanlungo Matsuhiro, Silvana; Nervi Oddone, Flavio