Cholecystokinin system is involved in the anorexigenic effect of peripherally applied palmitoylated prolactin-releasing peptide in fasted mice.

Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.

Pathophysiology of NAFLD and NASH in Experimental Models: The Role of Food Intake Regulating Peptides.

Obesity, diabetes, insulin resistance, sedentary lifestyle, and Western diet are the key factors underlying non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases in developed countries. In many cases, NAFLD further progresses to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and to hepatocellular carcinoma. The hepatic lipotoxicity and non-liver factors, such as adipose tissue inflammation and gastrointestinal imbalances were linked to evolution of NAFLD. Nowadays, the degree of adipose tissue inflammation was shown to directly correlate with the severity of NAFLD. Consumption of higher caloric intake is increasingly emerging as a fuel of metabolic inflammation not only in obesity-related disorders but also NAFLD. However, multiple causes of NAFLD are the reason why the mechanisms of NAFLD progression to NASH are still not well understood. In this review, we explore the role of food intake regulating peptides in NAFLD and NASH mouse models. Leptin, an anorexigenic peptide, is involved in hepatic metabolism, and has an effect on NAFLD experimental models. Glucagon-like peptide-1 (GLP-1), another anorexigenic peptide, and GLP-1 receptor agonists (GLP-1R), represent potential therapeutic agents to prevent NAFLD progression to NASH. On the other hand, the deletion of ghrelin, an orexigenic peptide, prevents age-associated hepatic steatosis in mice. Because of the increasing incidence of NAFLD and NASH worldwide, the selection of appropriate animal models is important to clarify aspects of pathogenesis and progression in this field.

Various AKIP1 expression levels affect its subcellular localization but have no effect on NF-kappaB activation.

A-kinase interacting protein 1 (AKIP1) has been shown to interact with a broad range of proteins involved in various cellular processes, including apoptosis, tumorigenesis, and oxidative stress suggesting it might have multiple cellular functions. In this study, we used an epitope-tagged AKIP1 and by combination of immunochemical approaches, microscopic methods and reporter assays we studied its properties. Here, we show that various levels of AKIP1 overexpression in HEK-293 cells affected not only its subcellular localization but also resulted in aggregation. While highly expressed AKIP1 accumulated in electron-dense aggregates both in the nucleus and cytosol, low expression of AKIP1 resulted in its localization within the nucleus as a free, non-aggregated protein. Even though AKIP1 was shown to interact with p65 subunit of NF-kappaB and activate this transcription factor, we did not observe any effect on NF-kappaB activation regardless of various AKIP1 expression level.

[Monitoring genotoxicity in the environment using cytogenetic methods such as chromosome analysis of peripheral lymphocytes, sister chromatid exchange and the micronucleus test]. / Sledovanie genotoxicity zivotného prostredia pomocou cytogenetických metód CALPL, SCE a MN-testu.

The work's aim is to observe environmental genotoxicity in the town of Ruzomberok and its surroundings in relation to the control group. The authors used three cytogenetic methods and compared their mutual sensitivity: chromosome analysis of human peripheral lymphocytes (CAHPL), micronuclear test (MN test) and differential staining of sister chromatides (SCE). The authors examined four groups of 30 children from the age of 6 to 8 years, originating from the localities of Cernová-Hrboltová, Stiavnica-Ludrová and Sliace. Individual localities are in various distances from the source of pollution (the industrial sewage treatment plant-STP and cellulose and paper factory-CPF). The control group contained children from the suburbs of Martin where no impact of industrial exhalations was assumed. For the purpose of evaluation of cytogenetic analysis results, nonparametric tests (K-S test and Z test) were used. The most sensitive method fo those used by the authors for the purpose of genotoxicity evaluation is CAHPL. The SCE method is less sensitive than CAHPL, but still more sensitive than MN test and suitable as a supplementary method for detection of exposition to genotoxic substances.