leptin and Gallstones

Obesity is one of the risk factors for gallstone disease (GD). Leptin hormone is known to regulate central obesity. Thus, hyperleptinemia may also be involved in gallstone disease pathogenesis. In the present study, a meta-analysis was performed to compare the leptin levels in GD and controls.. The authors reviewed studies till April 12, 2021, which reported the serum leptin levels in gallstone patients and healthy controls. The online search involved ScienceDirect and PubMed databases. The data obtained from the research articles was scrutinized for selection criteria. Only those articles which fulfilled the inclusion criteria were subjected to meta-analysis.. Of 2047 articles, a total of eight studies met the inclusion and exclusion criteria and were considered for the meta-analysis. After meta-analysis, it was observed that the patients with GD  had high leptin levels as compared to healthy controls. A significant level of heterogeneity was observed in the included studies (I. High leptin levels might be involved in GD pathogenesis.

Topics: Gallstones; Humans; Leptin; Obesity; Risk Factors

Gallstone disease is exceptionally common, occurring especially in Western populations, with cholesterol gallstones predominating. Currently, it is believed that obesity is the most consistent and important risk factor for the development of cholesterol gallstones. Obesity has been shown to be associated with the supersaturation of bile with cholesterol because of increased hepatic secretion of the sterol. In accord with current information from experimental studies, leptin appears to be involved in biliary cholesterol secretion and cholesterol gallstone formation in humans. This review summarizes the current information on the role of obesity in biliary lipid secretion as well as the effect of leptin and its potential consequences for gallstone formation and therapy in the obese.

Topics: Animals; Bile; Gallstones; Humans; Leptin; Lipid Metabolism; Obesity

Bile acid metabolism is a contributing factor that promotes cholelithiasis. Recent studies have suggested novel roles of leptin in the formation of gallbladder stones (GS); however, no evidence confirmed the function of leptin in the formation of primary intrahepatic bile duct stones (PIBDS) . In the current study, the liver tissues of patients with GS and PIBDS were collected to check the mRNA and protein expression levels of BSEP.. L02 cells stimulated with leptin were served for the expression of OB-Rb, AMPKα2, and BSEP by quantitative-polymerase chain reaction (q-PCR), Western blot, and immunohistochemistry, respectively.. The results showed that the level of serum leptin was higher in the GS group than in the control and PIBDS groups. Compared with the control group, the expression levels of OB-Rb, p-AMPKa2, and BSEP decreased significantly in the GS and PIBDS groups. In vitro, compared with the control cells, the protein levels of OB-Rb, p-AMPKa2, and BSEP increased in the L02 cells cultured with leptin. However, these enhancements disappeared when the cells were co-cultured with leptin plus Compound C.. The present results suggest that cholelithiasis, especially the formation of PIBDS, was connected with leptin, which could regulate bile acid metabolism through the OB-Rb/AMPKa2/BSEP signaling pathway.

Topics: Adult; Aged; AMP-Activated Protein Kinases; ATP Binding Cassette Transporter, Subfamily B, Member 11; Bile Acids and Salts; Bile Ducts, Intrahepatic; Cell Line; Cholelithiasis; Cross-Sectional Studies; Energy Metabolism; Female; Gallstones; Hepatocytes; Humans; Leptin; Liver; Male; Middle Aged; Receptors, Leptin; RNA, Messenger; Signal Transduction

To update information about comorbidity of non-alcoholic fatty liver disease (NAFLD) and gallstones disease (GD), evaluation of clinical and laboratory data, including insulin, leptin and adiponectin in individuals with NAFLD in combination with GD.. According to the design, we conducted an open comparative study of 169 patients with NAFLD. The following comparison groups were formed: group 1 (n=95) patients with NAFLD without GD, group 2 (n=35) patients with NAFLD and GD and group 3 (n=39) patients with NAFLD, GD and previous cholecystectomy.. A high prevalence of coronary heart disease was found in the group of patients with GD and cholecystectomy (2=6.198,p0.05); positive, statistically significant correlation relationships of cholelithiasis, cholecystectomy with ischemic heart disease (rs=0.172,p0.05 andrs=0.241,p0.05, respectively). There was a statistically significant decrease in total bilirubin and total protein in patients of group 3 (H=7.376,p0.03 and H=6.345,p0.04). The level of leptin is statistically significantly higher and positively interrelated with cholecystectomy (H=5.812,p0.05,rs=0.313,p0.05).. Patients with NAFLD, GD and previous cholecystectomy have a high prevalence of coronary heart disease; the phenomenon of insulin and leptin resistance, high level of adiponectin were revealed in patients with NAFLD and gallstones; hyperleptinemia was observed among patients with NAFLD, GD after cholecystectomy.. Цель исследования.Актуализация информации о коморбидности неалкогольной жировой болезни печени (НАЖБП) и желчнокаменной болезни (ЖКБ), оценка клинических, лабораторных данных, в том числе уровней инсулина, лептина и адипонектина, у лиц с НАЖБП в сочетании с ЖКБ. Материалы и методы.Согласно дизайну нами проведено открытое сравнительное исследование с включением 169 пациентов с НАЖБП. Сформированы следующие группы сравнения: группа 1 (n=95) пациенты с НАЖБП без ЖКБ, группа 2 (n=35) пациенты с НАЖБП и ЖКБ с сохраненным желчным пузырем и группа 3 (n=39) пациенты с НАЖБП и ЖКБ, перенесшие холецистэктомию. Результаты.Выявлена высокая распространенность ишемической болезни сердца (ИБС) в группе пациентов с ЖКБ, перенесших холецистэктомию (2=6,198;p0,05), обнаружены положительные статистически значимые корреляционные взаимосвязи ЖКБ, перенесенной холецистэктомии с ИБС (rs=0,172,p0,05 иrs=0,241,p0,05, соответственно). Отмечалось статистически значимое снижение уровня общего билирубина и общего белка у пациентов 3-й группы (H=7,376,p0,03 и H=6,345,p0,04). Уровень лептина статистически значимо выше и положительно взаимосвязан с холецистэктомией по результатам сравнительного и корреляционного анализа (H=5,812,p0,05,rs=0,313,p0,05). Заключение.Пациенты с НАЖБП, ЖКБ и перенесенной холецистэктомией имеют высокую распространенность ИБС; у пациентов, страдающих НАЖБП и ЖКБ, выявлен феномен инсулино- и лептинорезистентности, высокий уровень адипонектина; гиперлептинемия отмечена среди больных НАЖБП с ЖКБ после холецистэктомии.

Topics: Adiponectin; Cholecystectomy; Gallstones; Humans; Leptin; Non-alcoholic Fatty Liver Disease

To determine the relationships between serum leptin and levels of lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) in patients with cholelithiasis.. Patients with ultrasound-confirmed cholelithiasis and controls frequency-matched for age, sex, body mass index, fasting blood glucose and haemoglobin A1c levels were recruited. Fasting blood samples from all study participants were assayed for glucose, haemoglobin A1c, total cholesterol, high density lipoprotein-cholesterol (HDL-C) and triglyceride. Serum Lp(a), ApoA-1 and ApoB levels were measured using nephelometric assays; serum leptin was measured using an enzyme-linked immunosorbent assay.. A total of 90 patients with cholelithiasis and 50 controls were included in the study. Serum levels of leptin, Lp(a), total cholesterol, triglyceride and ApoB were significantly increased, and levels of ApoA-1 and HDL-C were significantly decreased, in patients with cholelithiasis compared with controls. Serum leptin in patients with cholelithiasis were significantly positively correlated with Lp(a) and ApoB and negatively correlated with ApoA-1.. Patients with cholelithiasis have higher leptin levels and an altered lipoprotein profile compared with controls, with increased leptin levels being associated with increased Lp(a) and ApoB levels, and decreased ApoA-1 levels, in those with cholelithiasis.

Topics: Apolipoprotein A-I; Apolipoproteins B; Blood Glucose; Body Mass Index; Cholelithiasis; Cholesterol, HDL; Female; Gallstones; Humans; Leptin; Male; Middle Aged

Levels of the hormones ghrelin and leptin in rat models of acute pancreatitis (AP) have been investigated in several experimental studies. However, there are very few clinical studies addressing the connection between hormone levels and AP. A few recent studies investigating the changes in ghrelin and leptin levels in patients with AP have been reported; however, our study is the first clinical study to investigate the change of nesfatin-1 levels in patients with gallstone-induced AP.. Forty patients were enrolled in this study, eight of which presented with severe AP. Two blood samples were obtained from each study patient. The first blood samples were obtained at patient admission to the hospital and the second was obtained at patient discharge. All samples were collected after at least 6 h of fasting. Plasma nesfatin-1, leptin, and ghrelin levels were measured.. In all 40 patients, nesfatin-1 and leptin levels were higher at admission and had decreased at discharge. In contrast, the ghrelin levels at discharge were significantly higher than those at admission. Only the changes in these hormones in the mild AP group were significant.. Levels of these hormones were altered during the course of gallstone-induced AP. These changes might be associated with the clinical outcomes of the disease. To clarify whether the magnitude of the change in hormone levels at AP onset can be used as a biomarkers to predict the severity of the disease requires further investigation.

Topics: Acute Disease; Adult; Aged; Calcium-Binding Proteins; DNA-Binding Proteins; Female; Gallstones; Ghrelin; Humans; Leptin; Male; Nerve Tissue Proteins; Nucleobindins; Pancreatitis; Predictive Value of Tests; Prognosis; Severity of Illness Index

A significant relationship exists among food intake and nutritional status and cholelithiasis, including gallstone and hepatolithiasis. Leptin is associated with obesity. This study was to investigate the differences in serum leptin levels in patients with gallstone and hepatolithiasis and to evaluate the relationships among leptin, cholecystokinin (CCK), lipid and lipoprotein concentrations.. Body mass index (BMI), serum leptin, CCK, insulin, lipid and lipoprotein concentrations, and liver function were measured in 382 patients with gallstone (GS group), 83 patients with hepatolithiasis (HS group) and 30 healthy controls (control group). The values of these indices were compared among the groups. In each group, Pearson's product-moment correlation coefficient among these indices were evaluated.. There were notable differences in serum leptin, CCK, total cholesterol, total triglycerides, apolipoprotein-a (APO-a), globulin, direct reacting bilirubin, and BMI between the GS and HS groups (P<0.05). Positive correlations between serum leptin and BMI, CCK, total cholesterol, gamma-glutamyl transpeptidase (GGT), aminotransferase, and insulin were found in the GS group (P<0.05). Positive correlations were observed between serum leptin and CCK, bilirubin, aminotransferase, GGT, in the HS group (P<0.05), but negative correlations between serum leptin and albumin or APO-a (P<0.05).. Leptin participates in modulating lipid metabolism. There are notable differences in leptin, serum lipid, and CCK between patients with gallstone and those with hepatolithiasis. The role of leptin in the pathophysiological course of cholelithiasis needs further investigation.

Topics: Adult; Aged; Apolipoproteins A; Bile Ducts, Intrahepatic; Bilirubin; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallstones; Globulins; Humans; Leptin; Lipid Metabolism; Lipoproteins; Male; Middle Aged; Triglycerides

Little is known about the genetic factors that cause alterations in gallbladder motility, cholesterol crystal nucleation, biliary lipids, and, ultimately, cholesterol gallstones. Obese, leptin-deficient (Lep(ob)) mice have large gallbladder volumes with decreased contraction in vitro and are predisposed to cholesterol crystal formation. Leptin administration to these mice causes weight loss and restores gallbladder function. We hypothesize that administration of leptin to Lep(ob) mice would cause weight loss, decrease gallbladder volume, and change gallbladder genes related to gallbladder motility, nucleating factors, and lipid metabolism.. Twenty-four 8-week-old Lep(ob) mice were fed a nonlithogenic diet for 4 weeks. Twelve mice received daily IP saline injections, and 12 received 5 mug/g recombinant leptin. Gallbladder mRNA was pooled and analyzed on murine genome microarray chips. Selected genes were confirmed by real-time polymerase chain reaction (PCR) in a second group of mice treated by the same protocol.. Leptin-deficient mice given leptin had significant weight loss and reductions in gallbladder volume. These mice had upregulation of the leptin receptor (p = 0.007; PCR = 1.1-fold increase) but downregulation of leptin (p = 0.003; PCR = 13.5-fold decrease). Leptin upregulated the cholecystokinin A receptor (p < 0.001; PCR = 3.1-fold increase), acetylcholine beta2 receptor (p = 0.005), and the Ca+-calmodulin-dependent protein kinase (p = 0.002) genes. Leptin also altered immunoglobulin heavy chain 4 (p = 0.005; PCR = 17.7-fold increase), mucin 3 (p = 0.006), and carboxylesterase (p = 0.016; PCR = 2.5-fold decrease) genes. Leptin downregulated 3-hydroxy 3-methylglutaryl coenzyme A reductase (p = 0.006; PCR = 2.5-fold decrease) and LDL receptor (p = 0.003).. Leptin modulates obesity and regulates gallbladder genes related to cholesterol gallstone pathogenesis.

Topics: Animals; Female; Gallbladder; Gallstones; Leptin; Mice; Mice, Obese; Obesity; Oligonucleotide Array Sequence Analysis; Organ Size; RNA, Messenger; Weight Loss

Gallstone disease has been regarded as an obesity-related disease. Therefore, we hypothesized that leptin and adiponectin, mainly produced by adipose tissue, may play roles in gallstone disease.. The RIA method was used to analyze serum leptin and adiponectin levels of 90 gallstone patients and 91 healthy subjects.. Our results showed that BMI, fasting glucose, serum AST and ALT, and leptin were significantly increased in the gallstone patients as compared with the healthy subjects (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.013, respectively). Intriguingly, serum adiponectin was the only variable to be significantly decreased in the gallstone patients (P = 0.002). Furthermore, serum AST, leptin, and adiponectin were significantly associated with gallstone disease (P < 0.001, P = 0.021, and P = 0.006, respectively). Overweight (BMI >or= 25 kg m(-2)), but not normal-weight, gallstone patients had an increased serum leptin and a decreased serum adiponectin level as compared with matched healthy subjects (P < 0.001 and P = 0.024, respectively). In addition, serum leptin was positively correlated with BMI and serum cholesterol, while serum adiponectin was inversely correlated with serum triglyceride in the gallstone patients.. Our study indicated that hyperleptinaemia and hypoadiponectinaemia might be involved in the occurrence of gallstone disease. However, the causal relationship of hyperleptinaemia and hypoadiponectinaemia with gallstone disease might require further investigation.

Topics: Adiponectin; Aspartate Aminotransferases; Body Mass Index; Cholesterol; Female; Gallstones; Humans; Leptin; Male; Middle Aged; Radioimmunoassay; Triglycerides

Both obesity and diabetes are associated with an increased incidence of gallstones. Recent animal and human data from our laboratory suggest that insulin resistance is associated with increased gallbladder volume and/or impaired gallbladder emptying. Pioglitazone is a thiazolidinedione that has been shown to improve insulin resistance. Therefore, we tested the hypothesis that pioglitazone would improve insulin resistance, decrease resting gallbladder volume and improve gallbladder response to neurotransmitters in insulin-resistant obese mice fed a 25% carbohydrate diet.. Twenty eight-week-old insulin-resistant obese (Lep(ob)) mice fed a 25% carbohydrate diet for 4 weeks. Half of the animals had 0.3 g/kg pioglitazone added to their diet. At 12 weeks all animals were fasted and underwent cholecystectomy. Gallbladder volume and weight were measured, and fresh gallbladders were placed in a muscle bath to assess response to acetylcholine (ACh 10(-5)M), neuropeptide Y (NPY 10(-8,-7,-6)M) and cholecystokinin (CCK 10(-10,-9,-8,-7)M). Serum glucose and insulin were measured, and HOMA Index, a measure of insulin resistance, was calculated.. Fasting serum insulin and HOMA Index were significantly decreased (P < 0.03), but gallbladder volume was significantly increased (P < 0.03) in the pioglitazone treated group. Pioglitazone did not alter gallbladder weight or response to ACh, NPY, or CCK.. These data suggest that in insulin-resistant obese mice pioglitazone 1) lowers insulin-resistance, 2) increases resting gallbladder volume, and 3) does not alter gallbladder response to neurotransmitters. Therefore, we conclude that pioglitazone, while improving insulin resistance, paradoxically increases gallbladder volume and, thereby, may increase the propensity for gallstone formation by enhancing gallbladder stasis.

Topics: Acetylcholine; Age Factors; Animals; Blood Glucose; Cholecystokinin; Cholinergic Agents; Dietary Carbohydrates; Female; Gallbladder; Gallstones; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Neuropeptide Y; Obesity; Organ Size; Peptide Fragments; Pioglitazone; Thiazolidinediones

Gallstones are strongly associated with higher parity in women. This study prospectively assessed the incidence, natural history, and risk factors for biliary sludge and stones during pregnancy and the postpartum in 3,254 women at an army medical center. Women with a prior cholecystectomy or with stones at their first study ultrasound were excluded. Gallbladder ultrasound and subject questionnaires were obtained in each trimester and at 4 to 6 weeks postpartum. Serum glucose, lipids, insulin, leptin, estradiol, and progesterone were measured at 26 to 28 weeks' gestation. A nested case-control study was done to examine the effects of serum leptin and insulin on incident gallbladder disease. At least two study ultrasounds were available for 3,254 women. Sludge or stones had been found on at least one study ultrasound in 5.1% by the second trimester, 7.9% by the third trimester, and 10.2% by 4 to 6 weeks postpartum. Regression of sludge and stones was common, such that overall 4.2% had new sludge or stones on the postpartum ultrasound. Twenty-eight women (0.8%) underwent cholecystectomy within the first year postpartum. Prepregnancy body mass index was a strong predictor of incident gallbladder disease (P < .001). Serum leptin was independently associated with gallbladder disease (odds ratio per 1 ng/dL increase, 1.05; 95% CI, 1.01, 1.11), even after adjusting for body mass index. In conclusion, incident gallbladder sludge and stones are common in pregnancy and the postpartum, and cholecystectomy is frequently done within the first year postpartum. Prepregnancy obesity and serum leptin are strong risk factors for pregnancy-associated gallbladder disease.

Topics: Adult; Bile; Case-Control Studies; Cholecystectomy; Female; Gallstones; Humans; Incidence; Leptin; Obesity; Postpartum Period; Pregnancy; Pregnancy Complications; Risk Factors

To establish an association between the serum leptin levels and the development of gallstone disease (GD).. We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate) stratified by BMI was used to calculate the risk of GD.. The multivariate conditional regression analysis revealed a model for those patients with BMI <30. The selected variables in the model were HOMA-IR index with OR = 1.31, P = 0.02 and leptin higher than median with OR = 2.11, P = 0.05. In the stratum of BMI >=30, we did not find a useful model.. We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.

Topics: Adult; Body Weight; Case-Control Studies; Female; Gallstones; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Regression Analysis

The absence of leptin due to the ob mutation leads to obesity and confers resistance to diet-induced cholesterol gallstone formation in otherwise susceptible C57BL/6J mice. To investigate contributions of obesity and leptin to gallstone susceptibility, C57BL/6J ob/ob mice were treated daily with i.p. saline or recombinant murine leptin at low (1 microgram/g bw) or high (10 microgram/g bw) doses and were pair-fed a lithogenic diet (15% dairy fat, 1.25% cholesterol, 0.5% cholic acid). Weight loss in ob/ob mice increased in proportion to leptin dose, indicating that the lithogenic diet did not impair leptin sensitivity. In a dose-dependent manner, leptin promoted cholesterol crystallization and gallstone formation, which did not occur in saline-treated mice. Notwithstanding, leptin decreased biliary lipid secretion rates without enriching cholesterol in bile. Leptin did not affect bile salt hydrophobicity, but did increase the biliary content of the most abundant molecular species of phosphatidylcholine, 16:0-18:2. Treatment with leptin down-regulated 3-hydroxy-3-methylglutaryl CoA reductase and prevented cholesterol from accumulating in liver. Consistent with increased hepatic clearance, leptin decreased plasma HDL cholesterol concentrations. This was accommodated in liver without up-regulation of cholesterol 7alpha-hydroxylase or Acat. These data suggest that despite the lithogenic diet, endogenous sources constitute a significant proportion of biliary cholesterol during leptin-induced weight loss. Kinetic factors related to cholesterol nucleation, gallbladder contractility, or mucin secretion may have accounted for leptin-induced gallstone formation.

Topics: Animals; Bile; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Dose-Response Relationship, Drug; Gallstones; Genetic Predisposition to Disease; Hydroxymethylglutaryl CoA Reductases; Leptin; Lipid Metabolism; Liver; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Time Factors; Triglycerides; Weight Loss