Saturation Of Bile Research Articles

Effects of Biliary Phospholipids on Cholesterol Crystallization and Growth in Gallstone Formation.

The prevalence of cholesterol gallstone disease is increasing, primarily due to the global epidemic of obesity associated with insulin resistance, and this trend leads to a considerable healthcare, financial, and social burden worldwide. Although phospholipids play an essential role in maintaining cholesterol solubility in bile through both mixed micelles and vesicles, little attention has been paid to the impact of biliary phospholipids on the pathogenesis of cholesterol gallstone formation. A reduction or deficiency of biliary phospholipids results in a distinctly abnormal metastable physical-chemical state of bile predisposing to supersaturation with cholesterol. Changes in biliary phospholipid concentrations influence cholesterol crystallization by yielding both liquid crystalline and "anhydrous" crystalline metastable intermediates, evolving into classical parallelogram-shaped cholesterol monohydrate crystals in supersaturated bile. As a result, five distinct crystallization pathways, A-E, have been defined, mainly based on the prime habits of liquid and solid crystals in the physiological or pathophysiological cholesterol saturation of gallbladder and hepatic bile. This review concisely summarizes the chemical structures and physical-chemical properties of biliary phospholipids and their physiological functions in bile formation and cholesterol solubility in bile, as well as comprehensively discusses the latest advances in the role of biliary phospholipids in cholesterol crystallization and growth in gallstone formation, largely based on the findings from clinical and animal studies and in vitro experiments. The insights gleaned from uncovering the cholelithogenic mechanisms are expected to form a fundamental framework for investigating the hitherto elusive events in the earliest stage of cholesterol nucleation and crystallization. This may help to identify better measures for early diagnosis and prevention in susceptible subjects and effective treatment of patients with gallstones.

Gall stones and hypothyroidism: a double jeopardy

Background: Gall stones are one of the frequent biliary pathologies in the biliary system. Gall stones are deposition of bile pigments, cholesterol and calcium salts in the form of hard crystalline mass in the gall bladder. Saturation of bile in gall bladder, bile stasis due to sphincter of Oddi dysfunction, biliary sludge and change in chemical disproportion of bile are all risk factors for gall stone development. Thyroid disorders are also a very common endocrine pathology. On the Oddi sphincter, thyroid hormone receptors are present, and thyroxine has a strong relaxing effect on the sphincter. Hypothyroidism reduces the gall bladder contractility and causes lipid metabolism alteration which leads to biliary stasis. These promote the gall stone formation.Methods: A single centre cross-sectional study, was done among 86 patients diagnosed with cholelithiasis clinically and confirmed by ultrasonography. All patients were subjected to thyroid profile test, liver function test, fasting lipid profile test. Patients with a history of hypothyroidism were excluded from the study.Results: Among 86 study subjects, 29 (33.7%) of study subjects had hypothyroidism, out of which 21 (24.4%) had subclinical hypothyroidism, 8 (9.3%) had clinical hypothyroidism. Of the remaining subjects 4 (4.7%) were hyperthyroid and 53 (61.6%) were Euthyroid. A total of 24 subjects had dyslipidaemia of which (15) 62.5% had clinical and sub clinical hypothyroidism (p<0.001).Conclusions: In the evolution of Gall stones in hypothyroid patients, decreased liver cholesterol metabolism, decreased bile emptying and decreased Oddi relaxation sphincter play a role. In our study there was a strong association between hypothyroidism and gall stones. Hypothyroid patients also had abnormal total cholesterol, triglycerides and ALP levels.

Association of Serum Iron and Ferritin Levels in Patients of Cholelithiasis: A Cross-Sectional Study

Background: Cholelithiasis is a common abdominal disorder resulting in increasing hospital admissions. About 10-12% of adults develop gallstones. Aim of this study was to find out any association of serum iron and ferritin levels in patients of cholelithiasis. Subjects and Methods: Present study was conducted at the department of surgery, tertiary care institute of for the period 1 year. For the study purpose 70 gall stone cases and 70 normal healthy matched controls were taken as study participants. After explaining about the study to the subjects, an informed consent will be obtained, followed by a detailed history with clinical examination with more emphasis on the parameters given below in outcome variable (ultrasonography finding, serum iron level, serum ferritin level, serum cholesterol). Results: The mean age in the case group (gallstones present) is 43.12 years, as compared to the control group the mean age is 41.05 years, The study shows in the case group 64% of patient was female and 36% was male and in the control group 76% of patient was female and 24% was male. In this study 46 (65.7%) patients with gallstones have the value of serum iron less than normal (normal value: >40 µg/dl). Our study shows, there are 35 female patients with gallstone disease who have serum iron levels below the normal value Most of the patients with gallstone disease whose serum iron levels are subnormal are females. Our study shows that the mean serum iron between cases and control was statistically significant p 0.05. There is no effect of anemia on serum cholesterol. In this study the mean serum cholesterol between cases and control was statistical insignificant (p>0.7)) In the case group, 20 of male and 36 of female patients have normal serum ferritin levels. The number of females having normal serum ferritin levels (in both case and control groups) is more. Conclusion: Gallstones are more prevalent in female population than males. Serum ferritin association is insignificant as it increases other condition with inflammation also. Low serum iron level associated with high risk of cholelithiasis as this may lead to super saturation of bile.

Correlation between Serum Iron, Serum Ferritin and Bile Cholesterol Level in Gallstone Disease

Introduction: The cholesterol stones are formed by super-saturation of the bile with cholesterol. Iron deficiency alters activity of several hepatic enzymes, leading to increased cholesterol saturation of bile in gall bladder thus promoting cholesterol crystallisation. Iron has a role in gallstone pathogenesis and ferritin is the most specific marker for iron levels in the body, but there are less studies which depict correlation between serum iron, serum ferritin and bile cholesterol. Aim: To study the correlation between serum iron, serum ferritin and bile cholesterol level in gallstone patients. Materials and Methods: The observational study was conducted in the Department of Surgery. The study population was 45 patients with gallstone disease. Serum iron, Serum ferritin and Bile cholesterol contents were analysed. Serum cholesterol levels were estimated using Folch method and estimation of bile cholesterol was done by Enzopak kit.Statistical analysis was done by using descriptive and inferential statistics using chi square test and software used in the analysis were SPSS 24.0 version and p<0.05 was considered as level of significance. Results: A positive but negligible correlation between serum iron and serum ferritin was observed (Pearson’s correlation coefficient of 0.247). Negative correlation between serum iron vs serum cholesterol and serum ferritin vs serum cholesterol was observed. Conclusion: It can be concluded that a low value of serum iron and serum ferritin is a risk factor for cholelithiasis, whereas, if the value of bile cholesterol increases then there is a high probability of cholelithiasis.

2334 Dapagliflozin, Diabetes, Liver Disease: With New Medications Come New Responsibilities

INTRODUCTION: Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is an oral hypoglycemic agent that was released in 2011. FDA approval was initially delayed due to concerns of hepatotoxicity. We present a case of drug induced liver injury (DILI) from dapagliflozin in a patient with newly diagnosed non-alcoholic fatty liver disease (NAFLD). CASE DESCRIPTION/METHODS: A 54-year-old Caucasian female with a history of obesity, diabetes mellitus, hyperlipidemia, and macular edema presented to the emergency room with new onset jaundice and intermittent episodes of confusion. She denied history of liver disease, recent travel, new or unusual foods, tattoos, incarcerations, previous blood transfusions, alcohol abuse, illicit substance use, or intake of herbal preparations. She started dapagliflozin one month prior for her diabetes. Her physical exam revealed scleral icterus and jaundice. Laboratory workup revealed total bilirubin 20.5, direct bilirubin 18.8, AST 228, ALT 222, alkaline phosphatase 1,145. She had a normal CBC, INR, ferritin, negative viral hepatitis panel, ASMA, AMA, and ANA. MRCP was unremarkable. Liver biopsy revealed a free hepatic venous pressure of 11 and wedged hepatic venous pressure of 14, and gradient was 3 mm Hg. Histology revealed cholestasis, several missing bile ducts, bile duct proliferation, portal edema from neutrophil related inflammation, and 35% steatosis with ballooning cells and stage 3-4 fibrosis. Dapagliflozin was stopped, and the patient's bilirubin and LFTs normalized over the next few months. DISCUSSION: With the incidence of type 2 diabetes mellitus projected to rise, novel medications are being introduced to treat patients. Obesity, metabolic syndrome, and diabetes are all risk factors for NAFLD, and currently the prevalence of NAFLD in this group is estimated at 75%. As patients with chronic liver disease have less hepatic reserve, physicians must identify signs of NAFLD or other chronic liver diseases prior to starting potentially hepatotoxic medications. Dapagliflozin is 1,200 times more specific for SGLT-2, but also has some inhibitory effects on SGLT-1, a cotransporter responsible for reabsorption of glucose from bile. SGLT-1 inhibition causes increased glucose saturation of bile, which can result in hepatocyte injury. It is pivotal to screen diabetics beforehand for NAFLD when considering hypoglycemic agents like dapagliflozin that may be hepatotoxic given the potential for acute liver failure as was seen in our patient.

Correlation of serum iron and ferritin levels in patients of cholelithiasis and comparison with healthy individuals

Background: Gall stones have afflicted man kinds since antiquity. Gall stone disease is prevalent, major source of morbidity and costly health problem. Presence of stones in the gallbladder is referred to as cholelithiasis, from the Greek chol-(bile)+lith (stone)+iasis-(process). If gallstones migrate into the ducts of the biliary tract, the condition is referred to as choledocholithiasis. Methods: It is case control study. Inclusion criteria were, patients aged above 18 years suffering from cholelithiasis confirmed by USG. The exclusion criteria were, patients having hematological disorder, having any systemic disease leading to iron deficiency, on drugs causing gallstones and pregnant females.Results: Study shows females were affected more in case (64%) and control (76%) group with mean age was of case (42.84 years) and control (40.64 years) group. 24% of patients was anaemic in cases. The mean serum cholesterol between cases and control was statistical insignificant (p=0.252). The mean serum ferritin between cases and control was statistical insignificant (p=0.800).Conclusions: The study of 100 cases, based on serum iron, serum cholesterol, serum ferritin and hemoglobin, concludes that the disease is more prevalent in female gender. Serum ferritin association is insignificant as it increases other condition with inflammation also. Low serum iron level associated with high risk of cholelithiasis as this may lead to super saturation of bile.

A Case Study on the management of Pittashmari w.s.r. to Gall Bladder Stone

Introduction: Ankylosing Spondylitis (AS) is a sero negative chronic inflammatory arthritis of Gall stone disease is a worldwide medical problem, but the incidence rates show substantial geographical variation, Cholelithiasis (gallstone formation) results from a combination of several factors, including super saturation of bile with cholesterol, accelerated nucleation of cholesterol monohydrate in bile, and bile stasis or delayed gallbladder emptying due to impaired gallbladder motility. In India it is more common in women in north, north-east and east as compared to other zones in the country. The disease Gall Stone has not been described directly in Ayurvedic classics. The word Ashmari in Ayurveda stands for stone which is described only in the context of Bastigata Ashmari (urinary calculi). After analyzing the Ayurvedic texts it was found that the bile secreted from gall bladder can be correlated with Accha Pitta mentioned in Ayurveda due to the similarity in location and function. The pathogenesis of the disease occurs due to the abnormal formation of Kapha during the process of digestion and its vitiation due to Vata. Once gallstones become symptomatic, definitive surgical intervention with cholecystectomy is usually indicated (typically, laparoscopic cholecystectomy is first-line therapy at centers with experience in this procedure). The present article deals with “Management of Pittashmari - A Case Study”

Serum iron and serum ferritin levels in cholelithiasis: a randomized study

Background: The role of iron in the pathogenesis of gallstone disease has not been well established so far. Iron deficiency has been shown to alter the activity of several hepatic enzymes, leading to increased cholesterol saturation of bile in gall bladder and hence promoting cholesterol crystallization.Serum iron, total iron binding capacity and transferrin saturation are not good indicators of iron status in individuals. In infection free situation, serum ferritin is an ideal indicator for diagnosis of iron deficiency.Methods: The study was conducted as a prospective study in the department of Surgery. The study population was divided into two groups; Case group with 200 patients with gallstone disease and control group with 50 patients without gallstone disease. Serum iron and ferritin contents of both groups will be analyzed and compared with each other.Results: In this study the gallstones are more prevalent in female population than males in ratio of 5.4:1. Serum iron in males was low in 41.93% not comparable 20.8% of control suggesting that low serum iron is not associated with Cholelithiasis in male. In males, serum ferritin was low in 64.5% of cases and 16.66% of controls. Serum ferritin levels were normal in 35.50% of cases and 66.66% of controls and above normal in 16.66% of controls suggesting that low serum ferritin is associated with gall stones in males. In this study, low serum iron was seen in 23.07% of females comparable to 23% low serum iron in control females and low ferritin was seen in 35.50% of female cases as compare to 15.38% of controls.Conclusions: It was concluded that a low body store of serum iron is a risk factor for cholelithiasis in females and serum iron, serum ferritin may be used as marker of iron store so that low serum iron status could be diagnosed at early stage.

Correlation of gallstone disease with iron deficiency anemia

Association between gallstone disease and iron deficiency anemia is not uncommon. The objective of this study was to assess correlation between gallstone formation and iron deficiency anemia in patients presenting with gallstone disease. Materials and Methods: A total of 60 patients' sonological evidence of gallstone were included in the study. Serum ferritin and serum iron levels were estimated. Gallstone patients were divided into anemic and non-anemic groups and compared with each other. Data were analyzed with descriptive statistical principles. Patients and Methods: Chi-square test or Fisher's exact test , Yates correction, independent t-test or Mann–Whitney U test. Results: There was significant association between serum iron and hemoglobin levels in patients with gallstone disease. This study suggests that iron deficiency leading to anemia plays a significant role in super saturation of bile, leading to stone formation in the gall bladder. Conclusions: Low serum iron and ferritin levels were found to be statistically significant in gallstone patients. Significant correlation found between iron deficiency and gallstone disease. Iron deficiency and low serum ferritin are probably independent risk factors operating for the causation of gallstones.

Laparoscopic Common Bile Duct Exploration for Choledocholithiasis During a Pregnancy: a Case Report

SummaryIn population studies, gallstones are found in 6.5% to 8.4% of nulliparous women, and in 18.4% to 19.3% of women with two to three or more pregnancies (7). Approximately 1 in 500 to 1 in 635 women will require non-obstetrical abdominal surgery during their pregnancies. Pregnancy induced physiological hormonal changes are associated with a decrease of gallbladder motility and increased cholesterol saturation of bile, leading to biliary stone formation (12,6,8). Surgical approach nowadays is the method of choice in the management of symptomatic gallstone disease during pregnancy, preferably if possible surgery should be postponed to second trimester (7,8).Preoperative radiologic imaging using magnetic resonance cholangiopancreatography is the golden standard for patients with suspected choledocholithiasis, however, its application during pregnancy is limited (9). Therapeutic endoscopic retrograde cholangiopancreatography (ERCP) may be used before, during or after laparoscopic cholecystectomy when it is indicated, but unfortunately, its application during pregnancy is associated with considerable number of complications concerning mother and fetus. Alternative approach has been developed and recommended for patients with the common bile duct (CBD) stones providing laparoscopic common bile duct exploration (LCBDE). Intraoperative cholangiography or intraoperative ultrasound (IOUS) are the methods currently used for detection of the CBD stones during laparoscopic cholecystectomy, however, IOUS can be considered as the method of choice during pregnancy (3).IOUS is a dynamic imaging modality that provides interactive and timely information during surgical procedures. Because the transducer is in direct contact with the organ being examined, high-resolution images can be obtained that are not degraded by air, bone, or overlying soft tissue (1).

The Concept of Cholelithiasis as Per Ayurvedic Text

Cholelithiasis (gallstone formation) results from a combination of several factors, including super saturation of bile with cholesterol, accelerated nucleation of cholesterol monohydrate in bile, and bile stasis or delayed gallbladder emptying due to impaired gallbladder motility. In India it is more common in women in north, north-east and east as compared to other zones in the country. The disease Gall Stone has not been described directly in Ayurvedic classics. The word Ashmari in Ayurveda stands for stone which is described only in the context of Bastigat Ashmari (urinary calculi). After analyzing the Ayurvedic texts it was found that the bile secreted from gall bladder can be correlated with Accha Pitta mentioned in Ayurveda due to the similarity in location and function. The pathogenesis of the disease occurs due to the abnormal formation of Kapha during the process of digestion and its vitiation due to Vata. The present article deals with description of formation of gall stone from the Ayurvedic perspective. Along with this the specific remedy for gall stone according to Ayurveda is also described.

Postmenopausal Estrogen Therapy and Risk of Gallstone Disease: A Population-Based Case–Control Study

Female gender and increasing age are key risk factors for gallstone disease; therefore, postmenopausal women are at high risk. Estrogen increases cholesterol saturation of bile and may further increase gallstone risk, but population-based evidence is sparse. Our objective was to examine the association between postmenopausal estrogen therapy and risk of gallstone disease and the impact of duration of treatment and use of opposing progestin. We conducted a population-based case-control study. Cases were postmenopausal women (defined as aged ≥45years) with gallstone disease identified in the period 1996-2010. For each case, we selected ten population controls matched to cases by age and sex. We defined exposure as any use of estrogen (opposed and unopposed by progestin). Cases/controls were categorized as current estrogen users if their last prescription was redeemed <90days before gallstone diagnosis (or corresponding date for controls); all other users were categorized as former users. The reference group consisted of cases/controls with no/rare estrogen use. Medical databases covering the population of Northern Denmark (2.4 million inhabitants through the period 1996-2010). We used conditional logistic regression to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of gallstone disease in women treated with estrogen. The ORs were adjusted for relevant comorbidity, other drugs known to influence gallstone risk, and parity. We identified 16,386 cases with gallstone disease and 163,860 controls. A total of 1,425 cases (8.7%) and 8,930 controls (5.4%) were current estrogen users, yielding an adjusted OR for gallstone disease of 1.74 (95% CI 1.64-1.85) compared with non-users. The corresponding adjusted OR for former users was 1.35 (95% CI 1.28-1.42). The results suggested a duration response for current users. Use of unopposed estrogen was associated with higher adjusted ORs than estrogen opposed by progestin. Postmenopausal estrogen therapy was associated with increased risk of gallstone disease in current and former estrogen users. Use of unopposed estrogen was associated with higher risk than use of estrogen opposed by progestin; this finding needs to be confirmed and explored further in future studies.

To study serum iron levels in patients of gall bladder stone disease and to compare with healthy individuals.

Gallstone disease is a common gastrointestinal problem in day-to-day practice. The Old concept that a typical gallstone sufferer is fat, fertile, flatulent female of 50. This is partially true as the disease has been found in women soon after their first delivery who are thin and underweight and in males also. Conditions that favor the formation of cholesterol gallstones are super saturation of bile with cholesterol, kinetically favorable nucleation and presence of cholesterol crystals in the gall bladder long enough to agglomerate into a stone. Recent studies have defined the role of trace elements (Fe, Ca, Zn and Cu) and defective pH in the formation of gallstones. The aim of the study was to correlate iron-deficiency anemia with gallstone disease. To estimate the serum ferritin level as a diagnostic tool of iron deficiency anemia in patients with gallstone disease, this prospective study of 100 patients was conducted over a period of 24months in the Department of General Surgery, Jaipur Golden Hospital, New Delhi, India. Serum cholesterol, iron and ferritin levels were compared in patients having gallstones and healthy individuals. A low serum iron level is a factor in bile super saturation with respect to cholesterol, leading to gallstone formation.

Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics.

Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease.

Genetic evidence that apolipoprotein E4 is not a relevant susceptibility factor for cholelithiasis in two high-risk populations

Apolipoprotein E (apoE) isoforms are genetic determinants of interindividual variations in lipid metabolism. To assess whether apoE is a genetic risk factor for cholesterol gallstone disease (GD), we analyzed apoE variants in populations from Chile and Germany, two countries with very high prevalence rates of this disease. ApoE genotypes were determined in Chilean gallstone patients (n = 117) and control subjects (n = 122) as well as in German gallstone patients (n = 184) and matched controls (n = 184). In addition, we studied apoE variants in subgroups of Chilean patients with strong differences in their susceptibility to acquire gallstones: 50 elderly subjects without gallstones in spite of well-known risk factors for this disease (gallstone-resistant) and 32 young individuals with gallstones but without risk factors (gallstone-susceptible). Furthermore, correlation analysis of apoE genotypes with cholesterol crystal formation times, biliary cholesterol saturation index (CSI), and gallstone cholesterol contents was performed in 81 cholecystectomized patients. In this study analyzing the largest sample set available, apoE4 genotype was not associated with an increased frequency of GD in either population. Moreover, in the Chilean population after adjusting for risk factors such as gender, age, body mass index, serum lipids, and glucose, the odds ratio for the association of the apoE4 allele and GD was significantly (P < 0.05) <1. Also, genotypes were not correlated with cholesterol crystal formation time, CSI, or gallstone cholesterol content. In contrast to previous smaller studies, apoE polymorphisms were not associated with susceptibility to cholesterol GD in high-risk populations.

Unconjugated bilirubin in human bile: the nucleating factor in cholesterol cholelithiasis?

Aims: To investigate the concentrations of bilirubin, bilirubin conjugates, phospholipid, and cholesterol in the gall bladder bile obtained at surgery from patients with and without cholesterol gallstones. Methods: Gall bladder...

Increases in biliary cholesterol-to-bile acid ratio in pregnant hamsters fed low and high levels of cholesterol.

Gallstones develop when the secretion of cholesterol is elevated compared with the secretion of bile acids into bile. One of the risk factors for the formation of gallstones is pregnancy. Because the pregnancy-induced increase in hepatic cholesterol synthesis rates could play a critical role in the development of cholesterol stones, the aim of the present study was to determine whether stone formation, as assessed by the ratio of cholesterol to bile acids in bile, could be ablated by blocking the pregnancy-induced increase in hepatic sterol synthesis rates. Golden Syrian hamsters were fed either ground chow or chow supplemented with 0.5% cholesterol for 3 wk and studied in the nonpregnant state or in late gestation. In chow-fed animals, a 1.6-fold increase in the ratio of cholesterol to bile acids occurred simultaneously with a sevenfold increase in hepatic sterol synthesis rate and a ninefold increase in the amount of newly synthesized cholesterol secreted into the bile in late gestation. In the cholesterol-fed dams, an increase in the ratio of cholesterol to bile acids occurred even with the lack of induction of hepatic sterol synthesis rates during pregnancy. Thus it appears that the marked induction of hepatic sterol synthesis rates during gestation is not essential for the pregnancy-induced cholesterol saturation of bile when cholesterol is fed to animals.

Aging per se is an independent risk factor for cholesterol gallstone formation in gallstone susceptible mice

Cholesterol gallstones occur rarely in childhood and adolescence and increase linearly with age in both genders. To explore whether aging per se increases cholesterol saturation of bile and gallstone prevalence, and to investigate age-related changes in hepatic and biliary lipid metabolism, we studied gallstone-susceptible C57L mice and resistant AKR mice of both genders fed 8 weeks with a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butter fat starting at (young adult) 8, (older adult) 36, and (aged) 50-weeks-of-age. After the 8-week feeding, gallstone prevalence, gallbladder size, biliary lipid secretion rate, and HMG-CoA reductase activity were significantly greater but cholesterol 7alpha-hydroxylase activity was lower in C57L mice of both genders compared with AKR mice. Increasing age augmented biliary secretion and intestinal absorption of cholesterol, reduced hepatic synthesis and biliary secretion of bile salts, and decreased gallbladder contractility, all of which increased susceptibility to cholesterol cholelithiasis in C57L mice. We conclude that aging per se is an independent risk factor for cholesterol gallstone formation. Because aging increases significantly biliary cholesterol hypersecretion and gallstone prevalence in C57L mice carrying Lith genes, it is highly like that Longevity (aging) genes can enhance lithogenesis of Lith (gallstone) genes.

Research Communication: Plasma Leptin and the Cholesterol Saturation of Bile Are Correlated in Obese Women after Weight Loss

Increased cholesterol secretion is a major alteration of biliary function in obese subjects Leptin is a regulator of food intake and is increased in plasma of subjects with low energy expenditure and high adiposity. We investigated the relationship between leptin and the cholesterol saturation of bile in obese women before and after weight reduction by energy restriction (5.02 MJ/d). We studied women (n = 14) with a body mass index (BMI) > or = 30 kg/m(2) who were 35.4 +/- 2.3 y old and who did not have a history of gallstones. They were studied by ultrasound to ensure absence of stones or sludge. BMI, gallbladder bile composition, plasma leptin, serum lipids and lipoproteins cholesterol levels were recorded at baseline and after 6 wk of weight reduction. There were decreases in BMI (33.9 +/- 3.1 to 31.1 +/- 3.6 kg/m(2), P < 0.0001) and leptin levels (16.7 +/- 9.7 to 10.0 +/- 6.7 micro mol/L, P < 0.05) during weight loss. After the experimental period, there were positive correlations between plasma leptin levels and BMI (r = 0.71, P < 0.004); leptin levels and the cholesterol saturation index (CSI) (r = 0.53, P < 0.05); the CSI and LDL cholesterol (r = 0.73, P < 0.003); and negative correlations between leptin levels and HDL cholesterol (r = -0.54, P < 0.05) and LDL cholesterol (r = -0.57, P < 0.03). We have shown relationships among HDL cholesterol, CSI and leptin. This could be useful in understanding the pathophysiology of cholesterol gallstone formation in obese people.

Gallstones in obesity and weight loss.

The prevalence of cholesterol gallstones is increased in obese persons. The risk is especially high in those with the highest body mass index (relative risk 5-6). Weight loss further increases the risk of gallstones: the prevalence of new gallstones reaches 10-12% after 8-16 weeks of low-calorie diet and more than 30% within 12-18 months after gastric by-pass surgery. About one-third of the stones are symptomatic. The increased prevalence of stones is mostly due to supersaturation of bile with cholesterol, because of an increased synthesis by the liver and secretion into bile. Saturation is further increased during weight loss. It returns toward normal after weight stabilization at a lower level, allowing spontaneous stone dissolution in some cases. Identified risk factors for gallstones during weight loss are a relative loss of weight greater than 24% of initial body weight, a rate of weight loss greater than 1.5 kg per week, a very low calorie diet with no fat, a long overnight fast period and a high serum triglyceride level. Ursodeoxycholic acid decreases cholesterol saturation of bile and gallstone incidence during weight loss. Other preventive measures include a control of weight loss rate, a reduction of the length of overnight fast, and maintenance of a small amount of fat in the diet.