Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol gallstones occur three times more frequently in morbidly obese subjects than in normal controls. The present study tests the hypothesis that obese subjects develop gallstones because of relative and absolute excess cholesterol excretion in bile. The steady-state kinetics of biliary lipid excretion and bile acid pool sizes were determined in eight healthy obese subjects without gallstones by a noninvasive technique. Aliquots of resting gallbladder bile were obtained on consecutive days. Hepatic bile excretion was constantly sampled during the infusion of a liquid isocaloric cholesterol-free formula containing a dilution indicator over two 12 hour periods on consecutive days. Gallbladder bile of seven of eight subjects was saturated consistently with cholesterol. Mean hourly hepatic cholesterol excretion in bile was 0.232 mM. per hour, three times greater than that of normal subjects and twice that of subjects with gallstones. Phospholipid and bile acid excretion were 0.73 and 1.88 mM. per hour, respectively. The excretion rates of these cholesterol-solubilizing components of bile are higher than in normal subjects but are insufficient to compensate for the increased cholesterol excretion. The bile acid pool sizes were normal (X = 2.72 Gm.) but the daily synthesis of bile acids was increased (X = 0.86 Gm. of cholic acid). We conclude that the clinically observed high correlation of cholelithiasis with obesity is due to increased hepatic secretion of cholesterol which precipitates as cholesterol gallstones.
 ...
PMID:The mechanism of increased gallstone formation in obese human subjects. 125 8

Cholesterol gallstones are a significant cause of morbidity in the U.S. Methods used to treat gallstones include cholecystectomy or medical dissolution. The primary drugs used for the dissolution of cholesterol gallstones are two bile acids, chenodeoxycholic acid and ursodeoxycholic acid. Complete or partial gallstone dissolution rates using chenodeoxycholic acid have ranged from 30 to 80 percent. Factors affecting gallstone dissolution using the bile acids include the dosage and administration schedule, obesity, the stone characteristics, diet, and the duration of therapy. The adverse effects of chenodeoxycholic acid include gastrointestinal complaints, hepatotoxicity, and increased serum cholesterol. Ursodeoxycholic acid, which is investigational, differs from chenodeoxycholic acid in its mechanism of action. Ursodeoxycholic acid has similar efficacy with chenodeoxycholic acid, at a lower daily dosage, with less gastrointestinal and hepatic adverse effects. If appropriate patient selection is used, the response rate to medical therapy can range from 50 to 80 percent.
 ...
PMID:Medical management of cholesterol gallstones. 351 22

Decreased activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolism of cholesterol to bile acids, is known to result in increased biliary cholesterol concentration and supersaturation of bile. Supersaturation of bile by cholesterol is a necessary condition for cholesterol gallstone formation. In guinea pigs, the hepatic concentration of ascorbic acid affects the catabolism of cholesterol: hypovitaminosis C reduces cholesterol 7 alpha-hydroxylase activity. Cholesterol gallstones are frequently found in ascorbic acid-deficient guinea pigs. Risk factors for cholesterol gallstones in humans include obesity, aging, estrogen treatment, pregnancy and diabetes. Plasma ascorbic acid levels are reduced in these groups. Vegetarian diets, which typically have high ascorbic acid contents, protect against gallstones. Since ascorbic acid effects the rate-limiting step in the catabolism of cholesterol in the guinea pig and many human risk groups for cholesterol gallstones are associated with reduced ascorbic acid levels, ascorbic acid may play a contributory role in human gallbladder disease.
 ...
PMID:Ascorbic acid and cholesterol gallstones. 845 79

Prevalence of gallstone disease in autopsies from Mexico is 14.3%, 8.4% in men and 20.4% in women respectively. Frequency of cholelithiasis has increased remarkably from 12.2% in 1950 to 15.8% in 1980 (p < 0.05). Population of low socioeconomic status is apparently more affected. Obesity is the clinical association more frequently found in the population studied. Cholesterol gallstones showed the highest frequency. Economic cost of this disease is high. We conclude that gallstone disease is a public health problem for our country.
 ...
PMID:[Epidemiology of gallstone disease in Mexico]. 1925 34

Cholesterol gallstones are among the most common gastrointestinal disorders in Western societies. Individuals with gallstones may experience various gastrointestinal symptoms and are also at risk of developing acute or chronic cholecystitis. Cholecystectomy is the most frequently recommended conventional treatment for symptomatic gallstones. Bile acids (ursodeoxycholic acid or chenodeoxycholic acid) are also used in some cases to dissolve radiolucent stones, but these drugs can cause gastrointestinal side effects and there is a high rate of stone recurrence after treatment is discontinued. Lithotripsy is used in some cases in conjunction with ursodeoxycholic acid for patients who have a single symptomatic non-calcified gallstone. There is evidence that dietary factors influence the risk of developing cholesterol gallstones. Dietary factors that may increase risk include cholesterol, saturated fat, trans fatty acids, refined sugar, and possibly legumes. Obesity is also a risk factor for gallstones. Dietary factors that may prevent the development of gallstones include polyunsaturated fat, monounsaturated fat, fiber, and caffeine. Consuming a vegetarian diet is also associated with decreased risk. In addition, identification and avoidance of allergenic foods frequently relieves symptoms of gallbladder disease, although it does not dissolve gallstones. Nutritional supplements that might help prevent gallstones include vitamin C, soy lecithin, and iron. In addition, a mixture of plant terpenes (Rowachol) has been used with some success to dissolve radiolucent gallstones. The gallbladder flush is a folk remedy said to promote the passage of gallstones. While minimal scientific evidence supports the efficacy of this treatment, anecdotal reports suggest the gallbladder flush may be beneficial for some people.
 ...
PMID:Nutritional approaches to prevention and treatment of gallstones. 1980 50

Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia) are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs) may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.
 ...
PMID:Current views on genetics and epigenetics of cholesterol gallstone disease. 2369 Dec 93