Degree of in vivo inhibition of human gastric and pancreatic lipases by Orlistat (Tetrahydrolipstatin, THL) in the stomach and small intestine

Sternby, Berit; Hartmann, D; Borgström, Bengt; Nilsson, Åke

doi:10.1054/clnu.2002.0565

Cited by 61 publications

(44 citation statements)

References 44 publications

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“…The 40% reduction in enterocyte LCFA uptake may not have been sufficient to impact overall absorption because of the large capacity of the small bowel for lipid uptake. Similarly, the gastric and pancreatic lipase inhibitor, Orlistat, only affects lipid absorption and weight gain after inhibiting more than 90% of lipase activity (31).…”

Section: Discussionmentioning

confidence: 99%

Targeted Deletion of Fatty Acid Transport Protein-4 Results in Early Embryonic Lethality

Gimeno

Hirsch

Punreddy

et al. 2003

Journal of Biological Chemistry

126

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Fatty acid transport protein-4 (FATP4) is the major FATP in the small intestine. We previously demonstrated, using in vitro antisense experiments, that FATP4 is required for fatty acid uptake into intestinal epithelial cells. To further examine the physiological role of FATP4, mice carrying a targeted deletion of FATP4 were generated. Deletion of one allele of FATP4 resulted in 48% reduction of FATP4 protein levels and a 40% reduction of fatty acid uptake by isolated enterocytes. However, loss of one FATP4 allele did not cause any detectable effects on fat absorption on either a normal or a high fat diet. Deletion of both FATP4 alleles resulted in embryonic lethality as crosses between heterozygous FATP4 parents resulted in no homozygous offspring; furthermore, no homozygous embryos were detected as early as day 9.5 of gestation. Early embryonic lethality has been observed with deletion of other genes involved in lipid absorption in the small intestine, namely microsomal triglyceride transfer protein and apolipoprotein B, and has been attributed to a requirement for fat absorption early in embryonic development across the visceral endoderm. In mice, the extraembryonic endoderm supplies nutrients to the embryo prior to development of a chorioallantoic placenta. In wild-type mice we found that FATP4 protein is highly expressed by the epithelial cells of the visceral endoderm and localized to the brush-border membrane of extraembryonic endodermal cells. This localization is consistent with a role for FATP4 in fat absorption in early embryogenesis and suggests a novel requirement for FATP4 function during development.

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Section: Discussionmentioning

confidence: 99%

Targeted Deletion of Fatty Acid Transport Protein-4 Results in Early Embryonic Lethality

Gimeno

Hirsch

Punreddy

et al. 2003

Journal of Biological Chemistry

126

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“…We found no inhibition activity for the phospholipase inhibitors D609, FIPI, and edelfosine (IC 50 >30 M, IC 50 >125 nM, and IC 50 >50 M, respectively). On the other hand, we observed inhibition of the ex vivo generation of 2-AG, 2-LG, and 2-OG in plasma spiked with Orlistat, a gastric and pancreatic lipase inhibitor ( 22 ) and a potent nonspecifi c inhibitor of DAGL ␣ and DAGL ␤ ( 23 ). It is to be noted that the artifactual generation of MGs persisted even after immediate sample centrifugation that essentially eliminates all blood cells, which means that this MG buildup should be related to an enzymatic plasma activity.…”

Section: Inhibition Experiments Of the Ex Vivo Generation Of Mgs Frommentioning

confidence: 99%

Analysis of ECs and related compounds in plasma: artifactual isomerization and ex vivo enzymatic generation of 2-MGs

Pastor

Farré

Fitó

et al. 2014

Journal of Lipid Research

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The neuromodulatory activities of the endocannabinoid (EC) system are involved in many human physiological and pathological functions ( 1-5 ). It comprises: i ) two Gprotein-coupled receptors, known as cannabinoid (CB)1 and CB2; ii ) endogenous ligands for these two receptors, known as ECs, N-arachidonoyl ethanolamine [AEA (anandamide)] and 2-arachidonoylglycerol (AG) being the most studied; and iii ) proteins that regulate EC tissue concentration (anabolic and catabolic enzymes), cellular distribution (EC-binding proteins and transporters), and CB receptor activity (CB receptor-interacting proteins) ( 1 ).In addition to AEA and 2-AG, there are a number of structurally related compounds, also known as EC-related compounds (ERCs), derived from less unsaturated fatty acids: N-acylethanolamides (

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“…Therapeutic doses of orlistat generally achieve around 35% inhibition of lipid digestion. 111,113,114 Thus as a consequence the undigested fat is not absorbed but excreted. 115 Beyond its lipase inhibition activity, orlistat reportedly does not significantly diminish the activity of other intestinal enzymes.…”

Section: Lipase Inhibitors Derived From Microbial Sources Lipstatinmentioning

confidence: 99%

The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

Tucci¹

2010

DMSO

117

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Degree of in vivo inhibition of human gastric and pancreatic lipases by Orlistat (Tetrahydrolipstatin, THL) in the stomach and small intestine

Cited by 61 publications

References 44 publications

Targeted Deletion of Fatty Acid Transport Protein-4 Results in Early Embryonic Lethality

Targeted Deletion of Fatty Acid Transport Protein-4 Results in Early Embryonic Lethality

Analysis of ECs and related compounds in plasma: artifactual isomerization and ex vivo enzymatic generation of 2-MGs

The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

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