NO-1886, a lipoprotein lipase activator, attenuates contraction of rat intestinal ring preparations.
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Various intestinal symptoms or diseases are closely associated with intestinal motility, which may be altered by metabolic disturbances associated with diabetes and obesity. It is therefore important that drugs used in the treatment of metabolic disorders should not have any adverse effects on the intestine. In the present study, we examined whether [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester (NO-1886), a lipoprotein lipase activator with anti-diabetic and/or anti-obese activity, affects stimulant-induced intestinal contractility. Administration of NO-1886 to intestinal ring preparations of ileum, rectum and colon isolated from Wistar rats attenuated or relaxed contraction induced by a high K+ environment or acetylcholine (ACh). This effect of NO-1886 was dependent on extracellular Ca(2+) and intracellular myosin light chain kinase activity. Our results also showed that ACh-induced colonic contraction was significantly higher in the obese Otsuka Long-Evans Tokushima Fatty (OLETF) than in the non-obese Long-Evans Tokushima Otsuka (LETO) rats. The hypercontractility observed in the colons of OLETF rats occurred concomitantly with an elevation in muscarinic M3 ACh receptor protein levels. Administration of NO-1886 attenuated the obesity-induced hypercontractility of the colonic rings of OLETF rats. Thus, intestinal contractile system would be a novel pharmacological target of the lipoprotein lipase activator NO-1886. (+info)
Ibrolipim increases ABCA1/G1 expression by the LXRalpha signaling pathway in THP-1 macrophage-derived foam cells.
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Hydrolysis of plasma triacylglycerol-rich lipoproteins from immature and laying hens (Gallus domesticus) by lipoprotein lipase in vitro.
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Very-low-density (VLD) lipoproteins and portomicrons were isolated from the plasma of immature and laying hens and their size, lipid composition and susceptibility to hydrolysis by lipoprotein lipase were compared. In agreement with other studies, VLD lipoproteins from laying hens were found to be smaller and have a different lipid composition than VLD lipoproteins from immature hens. Portomicrons from immature and laying hens had mean diameters of about 150 nm and similar lipid compositions. Hydrolysis of VLD lipoproteins from immature hens, and portomicrons from immature and laying hens, proceeded rapidly until at least 40% of the substrate had been used. In contrast only 1--15% of laying-hen VLD-lipoprotein triacylglycerol was readily hydrolysis occurred slowly. The limited susceptibility of laying-hen VLD lipoproteins appeared to be due to their low content of lipoprotein lipase activator apoprotein, which occurred despite an abundance of activator in the high-density lipoproteins of laying-hen plasma. The results provide further evidence that the liver of the laying hen synthesizes specialized lipoproteins. Their limited susceptibility to hydrolysis by lipoprotein lipase is probably a major factor in ensuring transport of lipid to yolk rather than to other tissues. The form of transport of dietary lipid, however, is similar in immature and laying hens. (+info)