Orlistat(Xenical(R), Roche) is considered a safe and effective drug to treat obesity by reduced absorption of 30% digested fat. To date, no serious adverse effects affecting the liver have been published except a case of subacute hepatic failure leading to liver transplantation in a young women with moderate obesity treated with orlistat. We report a case of acute cholestatic hepatitis in a young woman with moderate obesity treated with orlistat: a 33-year-old female admitted for the evaluation of jaundice. Abdominal ultrasonography, ERCP, routine chemistry, viral markers, and a fine needle biopsy of liver were performed. Microscopic findings of the liver biopsy specimen were compatible with acute cholestatic hepatitis. After steroid therapy, liver function was improved.
Acute Disease ; Adult ; Anti-Obesity Agents/*adverse effects ; Cholestasis/*chemically induced/diagnosis ; English Abstract ; Female ; Hepatitis, Toxic/*diagnosis/etiology ; Human ; Lactones/*adverse effects ; Lipase/antagonists & inhibitors

The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, (1)H NMR and (13)C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.
Adipocytes ; cytology ; drug effects ; Benzylisoquinolines ; chemical synthesis ; chemistry ; pharmacology ; Cell Proliferation ; drug effects ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Lipase ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship

To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acina response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.
Amylases/secretion ; Animal ; Benzodiazepinones/pharmacology ; Cells, Cultured ; Cholecystokinin/*pharmacology ; Devazepide ; Dose-Response Relationship, Drug ; Hormone Antagonists/pharmacology ; Lipase/secretion ; Male ; Pancreas/cytology/*drug effects/*secretion ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholecystokinin/antagonists & inhibitors ; Support, Non-U.S. Gov't

The present study was conducted to develop new inhibitors of pancreatic lipase and alpha-glucosidase from Chinese dietary herbs. Sixty-three dietary herbs from 39 taxonomic families were selected and extracted with aqueous ethanol or water. The extracts were then tested with in vitro enzyme assays for their ability to inhibit pancreatic lipase and alpha-glucosidase activities. Orlistat and acarbose were used as two positive controls. The extracts of Nelumbo nucifera, Curcuma longa, Piper longum and Morus alba showed strong pancreatic lipase inhibitory effects with IC50 at (28.00 +/- 5.51), (5.24 +/- 0.51), (14.76 +/- 2.58), (4.78 +/- 0.58), (3.41 +/- 0.67) mg x L(-1), respectively. These extracts also showed potent alpha-glucosidase inhibitory activities with IC50 at (1.98 +/- 0.13), (0. 18 + 0.007), (0.71 +/- 0.08), (0.077 +/- 0.005), (0.089 +/- 0.006) g x L(-1), respectively. The results provide useful information for developing new drugs or natural health products for hyperlipidemia and hypoglycemia from Chinese dietary herbs.
Curcuma ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Lipase ; antagonists & inhibitors ; Morus ; chemistry ; Nelumbo ; chemistry ; Pancreas ; enzymology ; Piper ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; alpha-Glucosidases ; metabolism

The present study was undertaken to explore whether retinoids, which are known to have immunomodulatory actions, could attenuate tumor necrosis factor-alpha (TNF)-stimulated inducible nitric oxide synthase (iNOS) expression in 3T3-L1 adipocytes. Adipocytes incubated with TNF induced dose- and time-dependent accumulation of nitrite in the culture medium through the iNOS induction as confirmed by Western blotting. Treatment of cells with TNF in the presence of all-trans-retinoic acid (RA) significantly decreased their ability to produce nitrite and iNOS induction. Both 13-cis- and all- trans-RA-induced suppression was dose-dependent, and all-trans-RA was somewhat potent than 13-cis-RA. The inhibitory effect of RA on TNF-induced iNOS induction was reversible, completely recovered after 2 days, and was exerted through the inhibition of NF-kappaB activation. TNF also suppressed the lipoprotein lipase (LPL) activity of 3T3-L1 adipocytes. RA could not reverse the TNF- induced LPL suppression at RA levels causing near complete inhibition of the TNF-induced NO production. These results indicate that RAs attenuate iNOS expression reversibly in TNF-stimulated 3T3-L1 adipocytes, and that the TNF- induced LPL suppression is not the result of NO overproduction.
3T3 Cells ; Adipocytes/drug effects/*enzymology/metabolism ; Animals ; Cells, Cultured ; Enzyme Induction/drug effects ; Enzyme Inhibitors/pharmacology ; Lipoprotein Lipase/drug effects/metabolism ; Mice ; NF-kappa B/antagonists & inhibitors ; Nitric Oxide/metabolism ; Nitric-Oxide Synthase/*antagonists & inhibitors/*metabolism ; Tretinoin/*pharmacology ; Tumor Necrosis Factor/pharmacology

OBJECTIVETo determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity.

METHODSA total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects. The body fat level of the subjects was determined at the same time by taking body weight, height and waist measurements. The thickness of the subcutaneous fat layer was also determined on the abdomen 3 cm to the right of the navel by the ultrasonic echo method. On the other hand, effects of oolong tea ingestion on plasma triglyceride (TG) and total cholesterol (TC) were determined. Inhibitions of pancreatic lipase by oolong tea extract and catechins in vitro were also determined.

RESULTSA total of 70% of the severely obese subjects did show a decrease of more than 1 kg in body weight, including 22% who lost more than 3 kg. Similarly, 64% of the obese subjects and 66% of the overweight subjects lost more than 1 kg during the experiment, and the subcutaneous fat content decreased in 12% of the subjects. The correlation between weight loss and subcutaneous fat decrease in men (r=0.055) was obviously lower than that in women (r=0.440, P<0.01). Body weight loss was signifificantly related to the decrease of the waist size in men (r=0.730, P<0.01) and women (r=0.480, P<0.01). Also, the correlation between subcutaneous fat reduction and decreased waist size was signifificant in women (r=0.554, P<0.01), but not in men (r=0.050, P>0.05). Moreover, the plasma levels of TG and TC of the subjects with hyperlipidemia were remarkably decreased after ingesting oolong tea for 6 weeks. In vitro assays for the inhibition of pancreatic lipase by oolong tea extract and catechins suggest that the mechanism for oolong tea to prevent hyperlipidemia may be related to the regulative action of oolong tea catechins in lipoprotein activity.

CONCLUSIONSOolong tea could decrease body fat content and reduce body weight through improving lipid metabolism. Chronic consumption of oolong tea may prevent against obesity.

Adult ; Aged ; Animals ; Beverages ; Body Height ; drug effects ; Body Weight ; drug effects ; Catechin ; pharmacology ; Cholesterol ; blood ; Diet ; Feeding Behavior ; drug effects ; Female ; Humans ; Lipase ; antagonists & inhibitors ; Male ; Middle Aged ; Obesity ; blood ; drug therapy ; Overweight ; blood ; drug therapy ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Subcutaneous Fat ; drug effects ; Sus scrofa ; Tea ; metabolism ; Triglycerides ; blood ; Young Adult

Parathyroid hormone-related protein (PTHrP) is synthesized by diverse tissues, and its processing produces several fragments, each with apparently distinct autocrine and paracrine bioactivities. In bone, PTHrP appears to modulate bone formation in part through promoting osteoblast differentiation. The putative effect of PTH-like and PTH-unrelated fragments of PTHrP on human mesenchymal stem cell (MSCs) is not well known. Human MSCs were treated with PTHrP (1-36) or PTHrP (107-139) or both (each at 10 nM) in osteogenic or adipogenic medium, from the start or after 6 days of exposure to the corresponding medium, and the expression of several osteoblastogenic and adipogenic markers was analyzed. PTHrP (1-36) inhibited adipogenesis in MSCs and favoured the expression of osteogenic early markers. The opposite was observed with treatment of MSCs with PTHrP (107-139). Moreover, inhibition of the adipogenic differentiation by PTHrP (1-36) prevailed in the presence of PTHrP (107-139). The PTH/PTHrP type 1 receptor (PTH1R) gene expression was maximum in the earlier and later stages of osteogenesis and adipogenesis, respectively. While PTHrP (107-139) did not modify the PTH1R overexpression during adipogenesis, PTHrP (1-36) did inhibit it; an effect which was partially affected by PTHrP (7-34), a PTH1R antagonist, at 1 microM. These findings demonstrate that both PTHrP domains can exert varying effects on human MSCs differentiation. PTHrP (107-139) showed a tendency to favor adipogenesis, while PTHrP (1-36) induced a mild osteogenic effect in these cells, and inhibited their adipocytic commitment. This further supports the potential anabolic action of the latter peptide in humans.
Adipogenesis/drug effects ; Alkaline Phosphatase/biosynthesis/genetics ; Antigens, Differentiation/biosynthesis/genetics ; Bone Marrow/pathology ; Cell Differentiation/drug effects ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/biosynthesis/genetics ; Culture Media ; Gene Expression Regulation ; Humans ; Lipoprotein Lipase/biosynthesis/genetics ; Mesenchymal Stem Cells/*drug effects/metabolism/pathology ; Osteoblasts/drug effects/*metabolism/pathology ; Osteogenesis/drug effects ; PPAR gamma/biosynthesis/genetics ; Parathyroid Hormone/*pharmacology ; Peptide Fragments/*pharmacology ; Receptor, Parathyroid Hormone, Type 1/antagonists & inhibitors