Detection of impaired intestinal absorption of long-chain fatty acids: validation studies of a novel test in a rat model of fat malabsorption.

Kalivianakis M, Minich DM, Havinga R, Kuipers F, Stellaard F, Vonk RJ, Verkade HJ.

Centre for Liver, Digestive and Metabolic Diseases, Groningen Institute for Drug Studies, Academic Hospital Groningen, Groningen, The Netherlands.

BACKGROUND: Classic fat balance studies detect fat malabsorption but do not discriminate between the potential causes of malabsorption, such as impaired intestinal lipolysis or reduced uptake of fatty acids. OBJECTIVE: We aimed to validate a novel test for the specific, sensitive detection of impaired intestinal uptake of long-chain unesterified fatty acids in an appropriate rat model of fat malabsorption. DESIGN: The absorption and appearance in plasma of [(13)C]palmitic acid were determined in control rats and in rats with fat malabsorption due either to chronic bile deficiency (permanent bile diversion) or to oral administration of the lipase inhibitor orlistat (200 mg/kg diet). [(13)C]Palmitic acid results were compared with the percentage absorption of ingested dietary fat determined by fat balance. RESULTS: Between 1 and 6 h after intraduodenal administration, plasma [(13)C]palmitate concentrations in control rats were 4-10-fold higher than in bile-deficient rats (P < 0.05) but were not significantly different between orlistat-supplemented rats and their controls. In control and bile-deficient rats, plasma [(13)C]palmitate concentrations allowed complete discrimination between normal (>92%) and reduced (<92%) fat absorption, whereas the percentage absorption of [(13)C]palmitate over 48 h appeared to be highly correlated with the percentage absorption of ingested dietary fat (r = 0.89, P < 0.001). CONCLUSIONS: The [(13)C]palmitic acid absorption test detects impaired intestinal absorption of long-chain fatty acids selectively and sensitively in a rat model of fat malabsorption due to bile deficiency. Our data strongly support the use of the [(13)C]palmitic acid absorption test for the diagnosis of clinical fat malabsorption syndromes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10871577&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


[Pharmacy-clinics medication of the month. Orlistate (xenical)]

[Article in French]

Scheen AJ, Ernest P, Letiexhe MR.

Service de Diabetologie, Nutrition et Maladies metaboliques, Universite de Liege.

Orlistat (tetrahydrolipstatin), launched by Roche under the trade name Xenical, is a selective inhibitor of pancreatic and gastro-intestinal lipases. It reduces the digestion of dietary fat and its resorption through digestive mucosa by around 30%. It is indicated, at a dose of 3 x 120 mg/day (one dose with each meal) and together with a moderately low-calorie and low-fat diet, for the treatment of obesity. It has been shown, in placebo-controlled two-year trials, to almost double the number of obese subjects who succeed in loosing at least 10% of initial body weight. Independently, it contributes to decrease serum cholesterol levels by 6-10%. Because of its mechanism of action, this drug can induce intestinal side-effects which tend to decrease with time and with the reduction of fat intake, thus improving diet compliance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10321111&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


The evaluation and treatment of the overweight patient.

Gonzalez A, Toy EC, Baker B.

St Joseph Hospital/CTMF Brackenridge Hospital-Austin, Obstetrics & Gynecology Residency Training Program, Houston, Texas, USA

Obesity represents one of the most important treatable causes of mortality and morbidity facing the primary care physician. Approximately one of every three U.S. adults is overweight or obese, leading to more than 300,000 preventable deaths each year. Because it is a multifactorial disorder involving food intake, physical activity, metabolism, and genetic factors, obesity is best treated with a coordinated approach. Diet and exercise remain the best initial treatment focus. Orlistat and sibutramine are recently developed medications reserved for obese patients who fail conservative therapy. Surgical remedies are indicated in limited circumstances for morbidly obese individuals. As primary care physicians, obstetrician/gynecologists are ideally positioned to motivate, evaluate, and treat overweight patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11077234&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic beta-cells (HIT).

Yaney GC, Civelek VN, Richard AM, Dillon JS, Deeney JT, Hamilton JA, Korchak HM, Tornheim K, Corkey BE, Boyd AE 3rd.

Evans Department of Medicine, Boston Medical Center, Massachusetts 02118, USA.

Glucagon-like peptide 1 (GLP-1) is the most potent physiological incretin for insulin secretion from the pancreatic beta-cell, but its mechanism of action has not been established. It interacts with specific cell-surface receptors, generates cAMP, and thereby activates protein kinase A (PKA). Many changes in pancreatic beta-cell function have been attributed to PKA activation, but the contribution of each one to the secretory response is unknown. We show here for the first time that GLP-1 rapidly released free fatty acids (FFAs) from cellular stores, thereby lowering intracellular pH (pHi) and stimulating FFA oxidation in clonal beta-cells (HIT). Similar changes were observed with forskolin, suggesting that stimulation of lipolysis was a function of PKA activation in beta-cells. Triacsin C, which inhibits the conversion of FFAs to long-chain acyl CoA (LC-CoA), enhanced basal FFA efflux as well as GLP-1-induced acidification and efflux of FFAs from the cell. Increasing the concentration of the lipase inhibitor orlistat progressively and largely diminished the increment in secretion caused by forskolin. However, glucose-stimulated secretion was less inhibited by orlistat and only at the highest concentration tested. Because the acute addition of FFAs also increases glucose-stimulated insulin secretion, these data suggest that the incretin function of GLP-1 may involve a major role for lipolysis in cAMP-mediated potentiation of secretion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11147795&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


[Evolution and weight and body composition determination after therapy for pathological obesity for measuring compliance in (re)-education]

[Article in French]

Keipes M, Fuente Martinez M, Nicolay L, Kuffer V, Mersch L, Klees J, Jacque M.

mkeipes pt.lu

Obesity, and its associated complications, is one of the most costly diseases in modern civilisations. Dieting alone rarely gives good long-term results. The effect of the combination of nutritional education and moderately intensive physical exercise on the evolution of weight and Body composition has been analysed by bio-impedancemetry over a one-year period. Patients could be divided into four groups: patients lost after the 3-week nutritional course, patients neither dieting nor exercising, patients dieting and patients both dieting and exercising. The results for the four groups were the following: undeterminably, 5% loss compared to initial weight (and nearly 10% compared to reported maximum weight). 10% loss and 15% loss over one year. In the last group, Body composition showed a relative increase in muscle mass, which explains the lack of a drop in basal metabolic rates seen in the diet-alone group. This maintained metabolic rate probably prevented patients from weight cycling (yo-yo phenomenon). This result can be compared to other life-style changing studies or pharmacological treatments (Orlistat, sibutramine) of obesity, which resulted in an approx. 10% weight reduction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11200309&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)