Serotonin receptor type 3 antagonists improve obesity-associated fatty liver disease in mice

ABSTRACT Obesity is a major cause for nonalcoholic fatty liver disease (NAFLD). Previous studies suggested that alterations in intestinal motility and permeability contribute to the development of NAFLD. Serotonin and serotonin receptor type 3 (5-HT 3 R) are key factors in the regulation of intestinal motility and permeability. Therefore, we studied the effect of the 5-HT 3 R antagonists tropisetron and palonosetron on the development of NA-FLD in leptin-deficient obese mice. Four-week-old ob/ob mice and lean controls were treated for 6 weeks orally with tropisetron or palonosetron at 0.2 mg/kg per day. We determined markers of liver damage and inflammation, portal endotoxin levels, and duodenal concentrations of serotonin, serotoninreuptake transporter (SERT), occludin, and claudin-1. Tropisetron treatment significantly reduced liver fat content (Ϫ29%), liver inflammation (Ϫ56%), and liver cell necrosis (Ϫ59%) in ob/ob mice. The beneficial effects of tropisetron were accompanied by a decrease in plasma alanine aminotransferase and portal vein plasma endotoxin levels, an attenuation of enhanced MyD88 and tumor necrosis factor-␣ mRNA expression in the liver, and an increase of tight junction proteins in the duodenum. Tropisetron treatment also caused a reduction of elevated serotonin levels and an increase of SERT in the duodenum of ob/ob mice. Palonosetron had similar effects as tropisetron with regard to the reduction of liver fat and other parameters. Tropisetron and palonosetron are effective in attenuating NAFLD in a genetic mouse model of obesity. The effect involves the intestinal nervous system, resulting in a reduction of endotoxin influx into the liver and subsequently of liver inflammation and fat accumulation

Estimating quantitative features of nanoparticles using multiple derivatives of scattering profiles

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Characterization of nanoparticles on surfaces is a challenging in verse problem whose solution has many practical applications. This article proposes a method, suitable for in situ characterization systems, for estimating quantitative features of nanoparticles on surfaces from scattering profiles and their derivatives. Our method enjoys a number of advantages over competing approaches to this inverse problem. One such advantage is that only a partial solution is required for the companion direct problem. For example, estimating the average diameter of nanoparticles to be 53 nm is possible even when a researcher’s existing scattering data pertain to nanoparticles whose average diameters are in multiples of 5 nm. Two numerical studies illustrate the implementation and performance of our method for inferring nanoparticle diameters and agglomeration levels respectively.NS