Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia.

Hatzitolios A, Savopoulos C, Lazaraki G, Sidiropoulos I, Haritanti P, Lefkopoulos A, Karagiannopoulou G, Tzioufa V, Dimitrios K.

First Propaedeutic Department of Internal Medicine, Ahepa General Hospital, Aristotelion University of Thessaloniki, Greece. aee med.auth.gr

AIM: To evaluate the efficacy and safety of three hypolipidemic agents in patients with non-alcoholic fatty liver disease associated with hyperlipidemia. METHODS: Patients with dyslipidemia (Fredrickson type IIb), asymptomatic persistent transaminasemia lasting 24 weeks, and evidence of hepatic fat infiltration on ultrasonography and liver biopsy were studied. Those with predominant hypertriglyceridemia received omega-3 fatty acids (5 mL thrice daily) (Group A), those with predominant hypercholesterolemia received atorvastatin 20 mg/daily (Group B), and overweight patients received orlistat 120 mg thrice daily before meals (Group C). After 24 weeks of treatment, serum transaminase and lipid levels and liver ultrasonography were repeated. RESULTS: Serum transaminase levels decreased significantly (p< 0.001) in all groups but the decrease was more marked in Group C (AST 75 [16] to 31 [7] IU/L; ALT 120 [38] to 41 [10] IU/L) than in Group A (AST 70 [14] to 41 [6]; ALT 110 [20] to 68 [12]) or Group B (AST 68 [13] to 46 [9]; ALT 115 [22] to 76.6 [13]). After treatment, ultrasonography showed resolution of fatty liver in 35% of patients in Group A, 61% in Group B, and in 86% in Group C (p< 0.001, Group C vs. A). CONCLUSIONS: A decline in transaminase levels and normalization of ultrasonographic evidence of fatty liver were observed on treatment with omega-3 fatty acids in patients with hypertriglyceridemia, with atorvastatin in those with hypercholesterolemia, and orlistat in overweight patients with hyperlipidemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15333967&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Addition of orlistat to conventional treatment in adolescents with severe obesity.

Ozkan B, Bereket A, Turan S, Keskin S.

Division of Paediatric Endocrinology, Department of Paediatrics, Ataturk University, Erzurum, Turkey.

To investigate the efficacy and tolerability of orlistat in obese adolescents, a prospective, open-label, randomised, controlled pilot trial was performed. A total of 22 adolescents with exogeneous obesity were started on orlistat (120 mg tid) and a daily multivitamin preparation in addition to conventional treatment which included nutritional and lifestyle modification programmes. The control group consisted of 20 obese adolescents who had similar duration of follow-up under conventional treatment alone. Of the 22 patients, 7 dropped out within the 1st month of the trial due to side-effects attributable to orlistat. The remaining 15 patients on orlistat were followed for 5-15 months (average duration of treatment 11.7+/-3.7 months). The control group was similar in age, sex, and duration of follow-up (10.2+/-3.7 months, range 6-17 months) to the orlistat group. Compared to initial body weight, patients in the orlistat group lost -6.27+/-5.4 kg, whereas those in the control group gained 4.16+/-6.45 kg ( P<0.001) during the study period. Patients in the orlistat group lost -7.65%+/-6.5% of their initial body weight, whereas, those of the control group gained 5.7%+/-8.3% ( P<0.001). The body mass index decreased in the orlistat group by -4.09+/-2.9 kg/m(2) while it increased by +0.11+/-2.49 kg/m(2) in the control group ( P<0.001). Mild gastrointestinal complaints (frequent stools) were experienced by all patients in the orlistat group. CONCLUSION:Orlistat could be a useful adjunct in the treatment of severe obesity in adolescents; however, gastrointestinal side-effects limit its usefulness in almost one in three adolescents.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15378354&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage.

Raz I, Eldor R, Cernea S, Shafrir E.

Department of Medicine, Diabetes Center, Hadassah University Hospital, Jerusalem 91120, Israel. ntv502 netvision.net.il

We present multiple findings on derangements in lipid metabolism in type 2 diabetes. The increase in the intracellular deposition of triglycerides (TG) in muscles, liver and pancreas in subjects prone to diabetes is well documented and demonstrated to attenuate glucose metabolism by interfering with insulin signaling and insulin secretion. The obesity often associated with type 2 diabetes is mainly central, resulting in the overload of abdominal adipocytes with TG and reducing fat depot capacity to protect other tissues from utilizing a large proportion of dietary fat. In contrast to subcutaneous adipocytes, the central adipocytes exhibit a high rate of basal lipolysis and are highly sensitive to fat mobilizing hormones, but respond poorly to lipolysis restraining insulin. The enlarged visceral adipocytes are flooding the portal circulation with free fatty acids (FFA) at metabolically inappropriate time, when FFA should be oxidized, thus exposing nonadipose tissues to fat excess. This leads to ectopic TG accumulation in muscles, liver and pancreatic beta-cells, resulting in insulin resistance and beta-cell dysfunction. This situation, based on a large number of observations in humans and experimental animals, confirms that peripheral adipose tissue is closely regulated, performing a vital role of buffering fluxes of FFA in the circulation. The central adipose tissues tend to upset this balance by releasing large amounts of FFA. To reduce the excessive fat outflow from the abdominal depots and prevent the ectopic fat deposition it is important to decrease the volume of central fat stores or increase the peripheral fat stores. One possibility is to downregulate the activity of lipoprotein lipase, which is overexpressed in abdominal relatively to subcutaneous fat stores. This can be achieved by gastrointestinal bypass or gastroplasty, which decrease dietary fat absorption, or by direct means that include surgical removal of mesenteric fat. Indirect treatment consists of the compliant application of drastic lifestyle change comprising both diet and exercise and pharmacotherapy that reduces mesenteric fat mass and activity. The first step should be an attempt to effectively induce a lifestyle change. Next comes pharmacotherapy including acarbose, metformin, PPARgamma, or PPARgammaalpha agonists, statins and orlistat, estrogens in postmenopausal women or testosterone in men. Among surgical procedures, gastric bypass has been proven to produce beneficial results in advance of other surgical techniques, the evidence basis of which still needs strengthening. Copyright (c) 2004 John Wiley & Sons, Ltd.

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xenical (orlistat)


A gastrointestinal lipase inhibitor reduces progression of atherosclerosis in mice fed a western-type diet.

Ueshima K, Akihisa-Umeno H, Nagayoshi A, Takakura S, Matsuo M, Mutoh S.

Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Kashima 2-1-6, Yodogawa-ku, Osaka 532-8514, Japan. koji_ueshima po.fujisawa.co.jp

To investigate whether gastrointestinal lipase inhibition reduces the progression of a western-type diet induced atherosclerosis, male apolipoprotein-E knockout (apoE KO) mice were administered orlistat ((S)-1-[[(S, 2S, 3S)-3-hexyl-4-oxo-2-oxetanyl] methyl]dodecyl-(S)-2-formamido-4-methylvalerate) mixed with a western-type diet for 8 weeks. Orlistat significantly reduced plasma triglyceride levels, but not total cholesterol levels, at 4 and 8 weeks of treatment. Increase in plasma triglyceride levels after oral olive oil loading in the mice fed a western-type diet was significantly suppressed in the orlistat treated group at 4 weeks of treatment. After 8 weeks treatment, atherosclerotic lesion area in the aorta of the orlistat treated group was significantly smaller than that of the control group. These results suggest that gastrointestinal lipase inhibition reduces the progression of atherosclerosis through a triglyceride-lowering effect, via inhibition of fat absorption.

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xenical (orlistat)


Lipid peroxides in obese patients and effects of weight loss with orlistat on lipid peroxides levels.

Yesilbursa D, Serdar Z, Serdar A, Sarac M, Coskun S, Jale C.

Cardiology Department, Uludag University Medical School, Bursa, Turkey. dilekyb uludag.edu.tr

OBJECTIVE: Obesity is a well-known risk factor of atherosclerosis. Recent studies showed that obesity is associated with enhanced lipid peroxidation. The aim of this study is to investigate the effect of weight reduction with orlistat treatment on lipid peroxidation levels. We assessed lipid peroxidation by measuring the concentration of plasma malondialdehyde (MDA). DESIGN: A randomized, controlled, open-label 6-month study. SUBJECTS: In total, 36 obese (body mass index (BMI) >30 kg/m2) and 11 healthy age-matched control subjects were enrolled in the study. MEASUREMENTS: Fasting glucose, triglyceride, total cholesterol, HDL cholesterol and LDL cholesterol and MDA levels were measured in both groups. Obese subjects received orlistat, 120 mg three times daily together with hypocaloric diet. After 6 months of treatment laboratory tests were repeated. RESULTS: MDA levels were significantly higher in obese patients than the control group (P<0.0001). After 6 months of treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Plasma MDA levels were significantly reduced by weight loss from 2+/-0.77 to 0.89+/-0.41 nmol/ml (P<0.001). BMI correlated with MDA levels at baseline (r=0.6, P<0.0001). Changes in BMI was positively associated with plasma MDA level reduction (r=0.36, P<0.05). CONCLUSION: These results indicate that obesity is associated with increases in endogenous lipid peroxides. Our data show that the indicator of lipid peroxidation-MDA-falls markedly in association with weight loss with orlistat. The demonstration of decreased free radical generation has important implications for oxidative mechanism underlying obesity-associated disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15467775&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)