Monosodium glutamate (MSG) treatment of neonatal mice results in a selective damage to the arcuate nucleus (ARC) and development of obesity with increased adiposity at sustained body weight in the adulthood. Feeding pattern of the MSG obese mice is unusual. Our previous results showed that after 24-h fasting, MSG mice consumed negligible amount of food in several hours and therefore, it was impossible to register the effect of peptides attenuating food intake such as cholecystokinin (CCK) or cocaine- and amphetamine-regulated transcript (CART) peptide. To overcome this problem, two findings were used: firstly, orexigenic effect of neuropeptide Y (NPY) was attenuated both by CCK or CART peptide in lean fed mice and secondly, orexigenic effect of NPY was preserved in fed rats with MSG obesity. In this study, short-term food intake in fed lean and MSG obese C57BL/6 male mice was measured after simultaneous central administration of orexigenic NPY with either CART peptide or peripherally administered CCK. Anorexigenic action of exogenous CART peptide was preserved in MSG obese mice. On the other hand, satiety effect of exogenous CCK was completely lost in MSG obese mice. In conclusion, effective leptin signaling in ARC is necessary for satiety effect of CCK., B. Železná ... [et al.]., and Obsahuje seznam literatury
Patients with obesity and type 2 diabetes often display high levels of the anti-diabetic factor fibroblast growth factor-21 (FGF21), suggesting that the overproduction of FGF21 may result from increased adiposity in an attempt by white adipose tissue (WAT) to counteract insulin resistance. However, the production of FGF21 diabetes in the absence of WAT has not been examined. In this study, we investigated the effects of lipodystrophy in A-ZIP F-1 mice on FGF21 production in relation to diabetes. A-ZIP F-1 mice displayed high FGF21 plasma levels resulting from enhanced FGF21 mRNA expression in the liver. Concomitant enhancement of FGF21 receptor (FGFR1) and glucose transporter 1 (GLUT-1) mRNA expression was observed in the muscles of A-ZIP F-1 mice. Furthermore, the activation of hypothalamic NPY and AgRP mRNA expression positively correlated with plasma levels of FGF21 but not active ghrelin. Our study demonstrates that an increased FGF21 plasma level in lipodystrophic A-ZIP F-1 mice results mainly from up-regulated liver production but does not suffice to overcome the lipodystrophy-induced severe type 2-diabetes and insulin resistance in the liver linked to the augmented liver fat deposition., A. Špolcová, M. Holubová, B. Mikulášková, V. Nagelová, A. Štofková, Z. Lacinová, J. Jurčovičová, M. Haluzík, L. Maletínská, B. Železná., and Obsahuje bibliografii
In this study, susceptibility of inbred C57BL/6 and outbred NMRI mice to monosodium glutamate (MSG) obesity or diet-induced obesity (DIO) was compared in terms of food intake, body weight, adiposity as well as leptin, insulin and glucose levels. MSG obesity is an early-onset obesity resulting from MSG-induced lesions in arcuate nucleus to neonatal mice. Both male and female C57BL/6 and NMRI mice with MSG obesity did not differ in body weight from their lean controls, but had dramatically increased fat to body weight ratio. All MSG obese mice developed severe hyperleptinemia, more remarkable in females, but only NMRI male mice showed massive hyperinsulinemia and an extremely high HOMA index that pointed to development of insulin resistance. Diet-induced obesity is a late-onset obesity; it developed during 16-week-long feeding with high-fat diet containing 60 % calories as fat. Inbred C57BL/6 mice, which are frequently used in DIO studies, both male and female, had significantly increased fat to body weight ratio and leptin and glucose levels compared with their appropriate lean controls, but only female C57BL/6 mice had also significantly elevated body weight and insulin level. NMRI mice were less prone to DIO than C57BL/6 ones and did not show significant changes in metabolic parameters after feeding with high-fat diet., R. Matyšková, L. Maletínská, J. Maixnerová, Z. Pirník, A. Kiss, B. Železná., and Obsahuje bibliografii a bibliografické odkazy
The incidence of metabolic syndrome increases in the developed countries, therefore biomedical research is focused on the understanding of its etiology. The study of exact mechanisms is very complicated because both genetic and environmental factors contribute to this complex disease. The ability of environmental fac tors to promote phenotype changes by epigenetic DNA modifications (i.e. DNA methylation, histone modifications) was demonstrated to play an important role in the development and predisposition to particular symptoms of metabolic syndrome. There is no doubt that the early life, such as the fetal and perinatal periods, is critical for metabolic syndrome development and therefore critical for prevention of this disease. Moreover, these changes are visible not only in individuals exposed to environmental factor s but also in the subsequent progeny for multiple generations and this phenomenon is called transgenerational inheritance. The knowledge of molecular mechanisms, by which early minor environmental stimuli modify the expression of genetic information, might be the desired key for the understanding of mechanisms leading to the change of phenotype in adulthood. This review provides a short overview of metabolic syndrome epigenetics., J. Kuneš, I. Vaněčková, B. Mikulášková, M. Behuliak, L. Maletínská, J. Zicha., and Obsahuje bibliografii
Ghrelin and agonists of its re ceptor GHS-R1a are potential substances for the treatment of cachexia. In the present study, we investigated the acute and lo ng-term effects of the GHS-R1a agonist JMV 1843 (H-Aib-DTrp-D-gTrp -CHO) on food intake, body weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose- dependent manner, up to 5-times relative to the saline-treated group (ED 50 =1.94 mg/kg at 250 min). JMV 1843 was stable in mouse serum in vitro for 24 h, but was mostly eliminated from mouse blood after 2 h in vivo . Ten days of treatment with JMV 1843 (subcutaneous administration, 10 or 20 mg/kg/day) significantly increased food intake, body weight and mRNA expression of the orexigenic neuropeptide Y and agouti-related peptide in the medial basal hy pothalamus and decreased the expression of uncoupling protein 1 in brown adipose tissue. Our data suggest that JMV 1843 could have possible future uses in the treatment of cachexia., M. Holubová, ... [et al.]., and Obsahuje seznam literatury
Neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr3ghrelin (Dpr3ghr), in SH-SY5Y neuroblastoma cells stressed with 1.2 mM methylglyoxal (MG), a toxic endogenous by-product of glycolysis, and we examined the impact of Dpr3ghr on apoptosis. Pre-treatment with both 10-5 and 10-7 M Dpr3ghr resulted in increased viability in SH-SY5Y cells (determined by MTT staining), as well as reduced cytotoxicity of MG in these cells (determined by LDH assay). Dpr3ghr increased viability by altering pro-apoptotic and viability markers: Bax was decreased, Bcl-2 was increased, and the Bax/Bcl-2 ratio was attenuated. The ghrelin receptor GHS-R1 and Dpr3ghr-induced activation of PBK/Akt were immuno-detected in SH-SY5Y cells to demonstrate the presence of GHS-R1 and GHS-R1 activation, respectively. We demonstrated that Dpr3ghr protected SH-SY5Y cells against MG-induced neurotoxicity and apoptosis. Our data suggest that stable ghrelin analogs may be candidates for the effective treatment of neurodegenerative disorders., A. Popelová, A. Kákonová, L. Hrubá, J. Kuneš, L. Maletínská, B. Železná., and Seznam literatury