Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines.

Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif W, Barnett AH, Kumar S.

Department of Diabetes and Endocrinology, Birmingham Heartlands Hospital, Birmingham, UK.

Modest weight loss if maintained is associated with significant metabolic benefits and reduction in cardiovascular risk. Adipose tissue secretes cytokines believed to contribute to the pathogenesis of insulin resistance and cardiovascular risk. We therefore observed the effect of modest weight loss on serum adipocytokines and their relationship with changes in anthropometric and metabolic parameters within a period of 6 months in the setting of a routine obesity hospital clinic after various medical treatments. In this prospective, nonrandomized, nonblinded observational study, patients were first given treatment (sibutramine or orlistat) as decided by the treating clinician and then allocated into 1 of 2 groups according to the treatment prescribed. The first group included 21 Caucasian nondiabetic female subjects, with a mean (+/-SD) age of 43 +/- 11 years and a mean body mass index (BMI) of 46 +/- 8.6 kg/m(2); subjects were treated with sibutramine 10 or 15 mg/d for weight loss. The second group included 20 Caucasian nondiabetic female subjects, mean age 42 +/- 9 years and mean BMI 45.2 +/- 5.2 kg/m(2); orlistat was introduced after 1 month on a low-fat (</=30%) diet in this group. Blood pressure and anthropometric measurements were performed before and after weight loss by a single observer. Serum glucose, insulin, lipid profile, C-reactive protein (CRP), resistin, leptin, and adiponectin were measured before and after weight loss on a fasting sample. After 6 months, the sibutramine group had a modest mean weight loss of 5.4% (P =.0001), and waist circumference was reduced by 4.5 +/- 1.4 cm. There was a decrease in serum resistin, leptin, and CRP levels, and a rise in serum adiponectin (P <.05). Change (%) (Delta) in BMI (DeltaBMI%) was associated with Deltainsulin(%) (P =.02, r = 0.53) and Deltaleptin(%) (P =.01, r = 0.58). Change in waist was associated with Deltainsulin(%) (P =.005, r = 0.75) and Deltaresistin(%) (P =.03, r = -0.55). The orlistat-treated group had a mean weight loss of 2.5%. Although this group did not show significant change in metabolic parameters, surprisingly there was a greater decrease of resistin (P =.02) associated with comparable (%) increase in adiponectin and (%) reduction of waist circumference and CRP. We conclude that modest weight loss (>5%) after medical treatment in a routine obesity hospital clinic is associated with improvements in insulin sensitivity and lipid profile. Modest weight loss is also associated with potentially favourably changes in serum adipocytokines, particularly in a rise of serum adiponectin. Reduction of waist circumference is associated with a change in serum resistin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15045687&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Effect of short-term weight loss on the metabolic syndrome and conduit vascular endothelial function in overweight adults.

Brook RD, Bard RL, Glazewski L, Kehrer C, Bodary PF, Eitzman DL, Rajagopalan S.

Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA. robdbrok umich.edu

Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15081445&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2.

Knowles LM, Axelrod F, Browne CD, Smith JW.

Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.

In eukaryotes, fatty acid synthase (FAS) is the enzyme responsible for synthesis of palmitate, the precursor of long-chain nonessential fatty acids. FAS is up-regulated in a wide range of cancers and has been suggested as a relevant drug target. Here, two independent approaches are taken toward knocking down FAS and then probing its connection to tumor cell proliferation. In one approach, Orlistat, a drug approved for treating obesity, is used as a potent inhibitor of the thioesterase function of FAS. In a separate strategy, the expression of FAS is suppressed by targeted knock-down with small interfering RNA. In both circumstances, the ablation of FAS activity causes a dramatic down-regulation of Skp2, a component of the E3 ubiquitin ligase that controls the turnover of p27Kip1. These effects ultimately tie into the retinoblastoma protein pathway and lead to a cell-cycle arrest at the G1/S boundary. Altogether, the findings of the study reveal unappreciated links between fatty acid synthase and ubiquitin-dependent proteolysis of cell-cycle regulatory proteins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15138278&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Fat malabsorption induced by gastrointestinal lipase inhibitor leads to an increase in urinary oxalate excretion.

Ferraz RR, Tiselius HG, Heilberg IP.

Nephrology Division, Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, Brazil.

BACKGROUND: Unabsorbed fat and bile acids may react with calcium in the intestinal lumen, limiting the amount of free calcium binding with oxalate and thereby raising intestinal oxalate absorption leading to hyperoxaluria. The aim of the present study was to determine whether orlistat (Xenical), a gastrointestinal lipase inhibitor, might increase urinary oxalate in an experimental rat model. METHODS: Thirty-nine male adult Wistar rats were fed a standard diet alone (controls) or supplemented with either 2% sodium oxalate (NaOx) or 3.2 mL of soy oil, or with both (NaOx + soy oil) for 4 weeks (diet period). Orlistat (16 mg/day) was added to the diet from the 5th to the 8th week (diet + orlistat period). Urinary oxalate (uOx), calcium (uCa), magnesium (uMg), and citrate (uCit) were determined and the ion-activity product of calcium oxalate [AP (CaOx) index(rat)] was estimated. RESULTS: Compared to baseline uOx significantly increased after diet + orlistat in controls (0.64 +/- 0.1 mg/24 hours vs. 0.56 +/-0.1 mg/24 hours), soy oil (0.80 +/- 0.3 mg/24 hours vs. 0.49 +/-0.2 mg/24 hours), and NaOx (2.48 +/- 0.8 mg/24 hours vs. 0.57 +/- 0.2 mg/24 hours), but the most marked increase occurred in NaOx + soy oil (3.87 +/- 0.7 mg/24 hours vs. 0.47 +/- 0.1 mg/24 hours). All groups except controls presented a significant reduction in uCa and uMg. Orlistat induced a significant increase in AP (CaOx) index(rat) compared, respectively, to baseline and to the diet period in NaOx (4.52 +/- 2.34 mg/24 hours vs. 0.94 +/- 0.86 and 1.53 +/- 0.93 mg/24 hours) and NaOx + soy oil (6.49 +/- 4.03 mg/24 hours vs. 0.54 +/- 0.17 and 1.76 +/- 1.32 mg/24 hours). CONCLUSION: These data suggest that the use of lipase inhibitors, especially under a diet rich in oxalate alone or associated with fat, leads to a significant and marked increase in urinary oxalate and a slight reduction in uCa and uMg that, taken together, resulted in an increase in AP (CaOx) index(rat), elevating the risk of stone formation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15253722&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Pouch dilatation following laparoscopic adjustable gastric banding: psychobehavioral factors (can psychiatrists predict pouch dilatation?).

Poole N, Al Atar A, Bidlake L, Fienness A, McCluskey S, Nussey S, Bano G, Morgan J.

Department of Mental Health, St. George's Hospital and Medical School, London, U.K.

BACKGROUND: Laparoscopic adjustable gastric banding is increasingly being performed in morbidly obese individuals for weight loss. Some patients develop pouch dilatation as a postoperative complication that limits the utility of the procedure. Surgical variables are poor predictors of this complication. 5 patients from a series of 157 who underwent LAGB at a single center developed the condition. METHODS: Psychiatric and surgical case-notes were analyzed retrospectively for the presence of operationally defined psychiatric disorders and compared to 10 controls from the same population. RESULTS: Cases were significantly more likely to have past or current binge eating, emotionally triggered eating with reduced awareness of the link, a history of affective disorder, reduced sexual functioning and successful preoperative weight loss. No difference between groups was observed for compliance with orlistat, childhood sexual abuse, relationships with parents, history of bulimia nervosa, rate of band inflation or preoperative BMI. CONCLUSIONS: Psychological factors may be better predictors of pouch dilatation than biomedical variables. Disordered eating can be an attempt to modulate negative emotions. Pouch dilatation may be a consequence of this eating behavior.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15318985&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)