-
1.
A high-carbohydrate diet effects on the A allele of hepatic lipase polymorphism on the apoB100/apoAI ratio in young Chinese males.
Hu, M, Li, Z, Fang, DZ
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2012;(6):751-7
Abstract
BACKGROUND Diet induces changes in plasma lipid profiles, and the plasma lipid profiles vary among different genetic backgrounds. OBJECTIVES The aim of this study was to investigate how a high-carbohydrate (high-CHO) diet interacts with hepatic lipase G-250A promoter polymorphism to affect the ratios of plasma lipids and apolipoproteins (apo) in a young Chinese population. MATERIAL AND METHODS Experiments were conducted on 56 university students. A stabilization diet was given for 7 days and a high-CHO diet was followed for 6 days. The diets used in this study were described by Song et al. and the following parameters were evaluated: total plasma triglyceride (TG), total plasma cholesterol (TC), plasma high-density lipoprotein cholesterol (HDL-C), plasma low-density lipoprotein cholesterol (LDL-C), apoB100 and apoAI. The plasma lipids and apoB100/apoAI ratios were also calculated and hepatic lipase G-250A polymorphism was analyzed. RESULTS At baseline, no significant difference was detected for subjects with different genotypes and genders. All the parameters showed significant differences before and after the high-CHO diet, and these differences are gender-specific: after the high-CHO diet, the TG/HDL-C ratios significantly increased in females (GG genotype: P = 0.004; A carriers: P = 0.005). The TC/HDL-C ratios significantly decreased in GG genotype males (P = 0.007), A carrier males (P < 0.0001) and A carrier females (P = 0.016) and the LDL-C/HDL-C ratios significantly decreased in the GG genotype males (P = 0.011), A carrier males (P < 0.0001) and A carrier females (P = 0.001). However, comparing the apoB100/apoAI ratio before and after the high-CHO diet, a significant difference only existed in male A carriers (P = 0.009). CONCLUSIONS The results of this study show that the high-CHO diet induces the positive effects on the lipid ratios in general, only except the TG/HDL-C ratio in females. Noticeably, the decreased apoB100/apoAI ratio is associated with the A allele of hepatic lipase G-250A polymorphism only in young Chinese males.
-
2.
Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans.
Sevastianova, K, Kotronen, A, Gastaldelli, A, Perttilä, J, Hakkarainen, A, Lundbom, J, Suojanen, L, Orho-Melander, M, Lundbom, N, Ferrannini, E, et al
The American journal of clinical nutrition. 2011;(1):104-11
-
-
Free full text
-
Abstract
BACKGROUND The rs738409 C→G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease. OBJECTIVE We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity. DESIGN We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([(2)H(5)]glycerol infusion) were measured before and after the diet. RESULTS At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 ± 0.5 kg; PNPLA3-148II: -3.1 ± 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P < 0.001) and by 18% in the PNPLA3-148II group (P < 0.01). CONCLUSION Weight loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775.
-
3.
Influence of intense multidisciplinary follow-up and orlistat on weight reduction in a primary care setting.
Feigenbaum, A, Pasternak, S, Zusk, E, Sarid, M, Vinker, S
BMC family practice. 2005;(1):5
Abstract
BACKGROUND Obesity is the most common health problem in developed countries. Recently, several physicians' organizations have issued recommendations for treating obesity to family physicians, including instructions in nutrition, physical activity and medications. The aim of this study was to examine if effective weight-reducing treatment can be given by a family physician. It compares regular treatment with intensive treatment that include close follow-up and orlistat treatment. METHODS The study was conducted in three primary care clinics. 225 patients were divided into three groups according to their choice. Group A received a personal diet with fortnightly meetings with the family physician and dietitian and orlistat treatment. Group B received a general diet, monthly meetings with the family physician only and orlistat treatment. Group C received a personal diet, monthly meetings with the dietitian only and no drug treatment. The primary endpoint was reduction of at least 5% of the initial weight during the study period. RESULTS A greater percentage of patients in group A achieved their weight reduction goals than in other groups (51%, 13% and 9% in groups A, B and C, respectively, p < 0.001). There was a significant reduction in triglycerides in all groups, a significant reduction of low density lipids (LDL) in groups A and B and no significant difference in high density lipids (HDL) in any group. CONCLUSIONS Significant weight reduction was obtained in a family physician setting. Further research is needed to evaluate if, by providing the family physician with the proper tools, similar success can be achieved in more clinics.
-
4.
Effect of Orlistat in obese patients with heart failure: a pilot study.
Beck-da-Silva, L, Higginson, L, Fraser, M, Williams, K, Haddad, H
Congestive heart failure (Greenwich, Conn.). 2005;(3):118-23
Abstract
Heart failure is the leading cause of hospitalization. Obesity is increasingly common and is a major public health problem. The aim of this study is to assess whether obese patients with heart failure can benefit from losing weight via an orlistat-assisted diet. This randomized clinical trial included obese patients with ejection fractions < or =40%. Orlistat and diet counseling were compared with diet counseling alone. Twenty-one consecutive obese patients with heart failure were recruited. Significant improvement in 6-minute walk test (45.8 m; 95% confidence interval, 5.2-86.4 m; p=0.031), functional class (-0.6+/-0.5, p=0.014), weight loss (-8.55 kg; 95% confidence interval, -13.0 to -4.1 kg; p<0.001) and also significant decreases in total cholesterol (p=0.017), low-density lipoprotein cholesterol (p=0.03), and triglycerides (p=0.036) were observed in the orlistat group. Orlistat can promote significant weight loss and symptoms of relief in obese patients with heart failure, as measured by 6-minute walk test and functional capacity. The lipid profile improved. Orlistat was safe and well tolerated.
-
5.
Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity.
Mathus-Vliegen, EM, Van Ierland-Van Leeuwen, ML, Terpstra, A
Alimentary pharmacology & therapeutics. 2004;(5):601-11
-
-
Free full text
-
Abstract
BACKGROUND Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction. AIM: To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation. METHODS Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months. RESULTS One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat. CONCLUSIONS One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.
-
6.
Influence of a lipase inhibitor on gastric sensitivity and accommodation to an orally ingested meal.
Demarchi, B, Vos, R, Deprez, P, Janssens, J, Tack, J
Alimentary pharmacology & therapeutics. 2004;(12):1261-8
-
-
Free full text
-
Abstract
BACKGROUND Intraduodenal administration of lipids, through lipid digestion and release of cholecystokinin (CCK), induces viscero-visceral reflexes that affect gastric tone and sensitivity. It is unclear whether the same mechanisms control gastric function after an orally ingested meal. AIM: To evaluate the effect of orlistat, a selective lipase inhibitor, on gastric response to an orally administered meal. METHODS Eighteen healthy volunteers participated in this study. They were treated for 5 days with orlistat (120 mg) or placebo t.d.s. in a double-blind randomized crossover design. During treatment, all subjects underwent a gastric barostat study, measurement of plasma CCK levels and a satiety drinking test. RESULTS Although CCK plasma levels were significantly decreased, pre-treatment with orlistat failed to affect gastric compliance (72 +/- 6 mL/mm Hg and 64 +/- 6 mL/mm Hg, NS), gastric sensitivity (discomfort threshold 12.2 +/- 0.6 mm Hg vs. 10.9 +/- 0.6 mm Hg above minimal distending pressure, NS) or gastric accommodation (172 +/- 41 mL vs. 206 +/- 49 mL, NS) to an orally ingested meal. Furthermore, orlistat pre-treatment had no significant effect on the amount of calories ingested during a satiety drinking test (1329 +/- 88 kcal vs. 1217 +/- 115 kcal, NS). CONCLUSION Administration of a lipase inhibitor does not affect gastric compliance, sensitivity to distension and accommodation to an orally ingested meal, and does not influence meal-induced satiety.
-
7.
Testosterone administration to men increases hepatic lipase activity and decreases HDL and LDL size in 3 wk.
Herbst, KL, Amory, JK, Brunzell, JD, Chansky, HA, Bremner, WJ
American journal of physiology. Endocrinology and metabolism. 2003;(6):E1112-8
Abstract
Testosterone administration to men is known to decrease high-density lipoprotein cholesterol (HDL-C) and the subclasses HDL(2) and HDL(3). It also might increase the number of small, dense, low-density lipoprotein cholesterol (LDL-C) particles in hypogonadal men. The decrease in HDL-C and in LDL-C size is potentially mediated by hepatic lipase activity, which hydrolyzes lipoprotein phospholipids and triacylglycerol. To determine how HDL-C and LDL-C particles are affected by testosterone administration to eugonadal men, testosterone was administered as a supraphysiological dose (600 mg/wk) for 3 wk to elderly, obese, eugonadal men before elective hip or knee surgery, and lipids were measured by routine methods and by density gradient ultracentrifugation. Hepatic lipase activity increased >60% above baseline levels, and HDL-C, HDL(2), and HDL(3) significantly declined in 3 wk. In addition, the LDL-C peak particle density and the amount of LDL-C significantly increased. Testosterone is therefore a potent stimulator of hepatic lipase activity, decreasing HDL-C, HDL(2), and HDL(3) as well as increasing LDL particle density changes, all associated with increased cardiovascular risk.
-
8.
Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers.
Carrière, F, Renou, C, Ransac, S, Lopez, V, De Caro, J, Ferrato, F, De Caro, A, Fleury, A, Sanwald-Ducray, P, Lengsfeld, H, et al
American journal of physiology. Gastrointestinal and liver physiology. 2001;(1):G16-28
Abstract
The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans. Orlistat was found to be a powerful gastric lipase inhibitor, achieving 46.6--91.4% enzyme inhibition and thus greatly reducing gastric lipolysis of solid and liquid meals (11--33% of respective controls). Gastric lipase inhibition by Orlistat was extremely fast (half-inhibition time < 1 min). Duodenal lipolysis was reduced significantly by Orlistat given with the solid meal (32.6--37.6% of controls) but was only slightly reduced by Orlistat given with the liquid meal (74.5--100% of controls). Human pancreatic lipase (HPL) inhibition was found to be high (51.2--82.6%), however, regardless of the meal. These paradoxical results were explained when in vitro lipolysis experiments were performed. The rates of HPL inhibition by Orlistat were found to be similar with both types of meals (half-inhibition time 5--6 min), but the preemulsified triglycerides of the liquid meal were rapidly hydrolyzed by HPL before the enzyme was significantly inhibited by Orlistat. With the solid meal, the rate of hydrolysis of the meal triglycerides by HPL was slower than the rate of HPL inhibition by Orlistat. As predicted from the previous results, the effects of Orlistat on fat excretion levels were found to be much greater with the solid (40.5--57.4% of ingested fat) than with the liquid (4.2--18.8%) test meal.
-
9.
Orlistat inhibits dietary cholesterol absorption.
Mittendorfer, B, Ostlund, RE, Patterson, BW, Klein, S
Obesity research. 2001;(10):599-604
Abstract
OBJECTIVE Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration. RESEARCH METHODS AND PROCEDURES Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous administration of intravenous ([(2)H(6)] cholesterol) and oral ([(2)H(5)] cholesterol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption. RESULTS In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 +/- 5% and 51 +/- 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 +/- 6% to 44 +/- 5% (p < 0.01). DISCUSSION These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.
-
10.
Promoter polymorphisms of hepatic lipase gene influence HDL(2) but not HDL(3) in African American men: CARDIA study.
Juo, SH, Han, Z, Smith, JD, Colangelo, L, Liu, K
Journal of lipid research. 2001;(2):258-64
Abstract
Hepatic lipase encoded by the hepatic lipase gene (LIPC) is involved in the metabolism of several lipoproteins. Four promoter polymorphisms in LIPC have been found to be in complete disequilibrium and associated with high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo)A-I levels in both white and black populations. We investigated the association between the promoter polymorphism and lipid profiles as well as anthropometric phenotypes in African American men in the Coronary Artery Risk Development in Young Adults study. We performed serial cross-sectional analyses and longitudinal analyses of lipids from 578 subjects in five examinations over 10 years of follow-up. Results showed that the allele frequency (0.52) in our black population was consistent with that reported in black subjects but much higher than that reported (approximately 0.2) in white populations. Analysis of covariance tests of the three genotypic means in each examination showed that the P values ranged from 0.01 to 0.08 for HDL-C (except P = 0.54 in the fourth examination), from 0.006 to 0.01 for HDL(2)-C, and from 0.06 to 0.07 for apoA-I. Mean HDL(3)-C levels were essentially identical among the three genotypes. Total cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, and apoB, which are mainly involved in the very low density lipoprotein-LDL pathway, were not significantly different according to the promoter polymorphism, except for triglycerides in the third examination (P = 0.01). No significant association was found between anthropometric phenotypes and the LIPC polymorphism in any of five examinations. The change of the anthropometric variables was not significantly associated with genotypes. In conclusion, our results indicated that the LIPC promoter polymorphism has exclusive effects on HDL(2)-C but not HDL(3)-C levels.