Body weight, diet and fluid intake were assessed weekly

Body weight, diet and fluid intake were assessed weekly. RT-PCR, western blot or immunoassays. For statistical analysis t-test and one-way ANOVA with Tukeys post hoc test and Bartletts test for equivalent variances was used. == Results == Hepatic triglycerides, liver weight and liver to body weight ratio were significantly changed depending on the extra fat quality but not extra fat quantity. In contrast, extra fat quantity but not quality decreased the expression of the limited junction proteins occludin and claudin-1 in the small intestine. These changes seemed to result in enhanced portal vein endotoxin concentrations and fatty liver disease after feeding diet enriched with saturated and monounsaturated fatty acids but not polyunsaturated fatty acids. Neither fatty acid amount nor quality significantly affected the intestinal serotonergic system. Similarly, tryptophan supplementation experienced no impact on small intestinal barrier or fatty liver disease. == Summary == In conclusion, diet programs rich in saturated or monounsaturated fatty acids promote the development of fatty liver disease in mice, likely by a dysfunction of the small intestinal mucosal barrier. Keywords:Non-alcoholic fatty liver disease, Saturated, Monounsaturated, Polyunsaturated fatty acids in diet, Serotonin, Intestinal permeability == Background == Non-alcoholic fatty liver disease (NAFLD) is one of the most important forms of liver disease in the developed countries, happening in 20% to 25% of the general human population [1,2]. Diet and lifestyle habits leading to obesity and insulin resistance are believed to exert the main pathophysiological part in the development of NAFLD [3-5]. Among the diet factors, high extra fat intake and high sugars intake (Western-style diet) are thought to be of particular relevance [6]. In earlier studies performed in mice, we could show that within the sugars, fructose plays a particular role for the development of NAFLD, whereas glucose is more relevant with regard to body weight [7]. Other studies suggested that a high extra fat intake, for example saturated fatty acids (SFA), is critical for both, the development of obesity and NAFLD [6,8,9]. In contrast, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) have been attributed rather to a healthy diet [10]. The mechanisms of diet-induced NAFLD are undoubtedly not clear at present. Based on previously published studies, we while others hypothesized that one possible mechanism of NAFLD development is an modified gastrointestinal (GI) barrier function. GI barrier dysfunction may be caused by particular diet programs or diet components resulting in an impaired mucosal barrier and an elevated portal endotoxin level [11]. The Rabbit Polyclonal to Claudin 1 endotoxin enters the liver where it is identified by Toll-like receptors (TLR) and causes innate immune reactions and swelling [12-14]. Evidence is definitely increasing that high intake of diet sugars may lead to improved portal endotoxin levels and as a result activation of TLRs [15]; however, the mechanisms by which high intake of diet fatty acids cause obesity and fatty liver disease remain elusive. Apart from the translocation hypothesis, stating that an impaired GI barrier prospects to translocation of endotoxin from your gut lumen to the liver and causing fatty liver disease, additional mechanisms might be regarded as. For example, serotonin (5-HT) derived from enterochromaffin cells, has been recognized as a potent pro-inflammatory mediator [16] and major regulator of intestinal permeability [14]. Interestingly, we could display that 5-HT is definitely VU6005649 up-regulated in mice fed a fructose-rich diet and that liver steatosis induced by such a diet can be attenuated by suppressing 5-HT signaling [17]. The precursor of 5-HT is the amino acid tryptophan VU6005649 (TRP), which is also known to be a regulator of intestinal motility [18,19]. TRP has been used to alter the intestinal serotonin homeostasis, since intra peritoneal treatment with TRP enhances 5-HT levels [20,21]. Remarkably, it also has been reported that TRP is definitely capable of reducing hepatic lipid build up in particular VU6005649 animal models [22,23] and plasma triglycerides in humans [24]. In addition, TRP is able to exert anti-inflammatory effects in the liver [25]. Here, we analyzed potential mechanisms leading to the development of diet-induced fatty liver disease. We fed three types of fatty acid enriched diet VU6005649 programs with or without TRP product and investigated the effect of these diet programs within the intestinal barrier function, fatty liver disease and the intestinal serotonergic system in mice. == Methods == == Mice and treatments == Mice were housed inside a pathogen-free barrier facility accredited from VU6005649 the Association for Assessment and Accreditation for Laboratory Animal Care International (AAALAC). All methods were authorized by the local Institutional Animal Care and Use Committee (Regional Council Stuttgart). Female 6 weeks older C57BL/6 mice (Janvier,.