Ovariectomized mice on a high fat diet represent a model of diet-induced obesity during estrogen deficiency. Here, we tested the hypothesis that sensitivity to centrally administered leptin in ovariectomized mice with diet-induced obesity could be restored by estrogen supplementation. Ovariectomized C57BL/6 female mice were fed either a standard or high fat diet until they were 27 weeks old. Ovariectomized mice on a high fat diet developed extreme obesity and hyperleptinemia and moderate hyperinsulinemia compared to those on a standard diet. For the last 4 weeks, 17beta-estradiol-3-benzoate or its vehicle was administered subcutaneously in a 4-day cyclic regimen. Finally, leptin or saline was injected into the third ventricle, and food intake and body weight were measured for 36 h. In ovariectomized mice fed a standard diet, the decrease in food intake and body weight was significant and was pronounced in 17beta-estradiol-3-benzoate-supplemented mice. The response to centrally injected leptin in ovariectomized mice on a high fat diet was insignificant, whereas in 17beta-estradiol-3-benzoate-supplemented mice, the effect was significant, particularly with respect to body weight. We showed for the first time that central insensitivity to leptin in ovariectomized diet-induced obese mice was restored with 17beta-estradiol-3-benzoate supplementation, which also attenuated most of the parameters of metabolic syndrome. Only circulating adiponectin, a peripheral insulin sensitivity marker, was lowered following 17beta-estradiol-3-benzoate administration in both high fat and standard diet-fed ovariectomized mice, despite of decreased or unchanged glycemia, respectively.

• MeSH
• dieta MeSH
• dietní tuky aplikace a dávkování   farmakologie   MeSH
• estradiol aplikace a dávkování   farmakologie   MeSH
• hmotnostní přírůstek účinky léků   MeSH
• leptin aplikace a dávkování   farmakologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita metabolismus   MeSH
• ovarektomie MeSH
• potravní doplňky MeSH
• stravovací zvyklosti účinky léků   MeSH
• tělesná hmotnost účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• cholecystokinin fyziologie   MeSH
• financování organizované MeSH
• glutamát sodný MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neuropeptid Y fyziologie   MeSH
• nucleus arcuatus hypothalami fyziologie   MeSH
• obezita chemicky indukované   patofyziologie   MeSH
• proteiny nervové tkáně fyziologie   MeSH
• regulace chuti k jídlu MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

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 MSGinduced 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.

• Klíčová slova
• C57BL/6, NMRI, Mouse, Monosodium glutamate obesity, Diet-inducet obesity,
• MeSH
• adipozita MeSH
• dietní tuky MeSH
• druhová specificita MeSH
• fenotyp MeSH
• financování organizované MeSH
• glutamát sodný MeSH
• inzulin krev   MeSH
• inzulinová rezistence MeSH
• krevní glukóza metabolismus   MeSH
• leptin krev   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• novorozená zvířata MeSH
• nucleus arcuatus hypothalami metabolismus   patofyziologie   MeSH
• obezita etiologie   metabolismus   patofyziologie   MeSH
• přijímání potravy MeSH
• tělesná hmotnost MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

BACKGROUND: CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin (CCK) are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS), the paraventricular nucleus (PVN), and the dorsomedial nucleus (DMH) of the hypothalamus. RESULTS: In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102) in the doses of 0.1 or 0.5 microg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 microg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102) on food intake. After simultaneous administration of 0.1 microg/mouse CART(61-102) and of 4 microg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102) and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test. CONCLUSION: The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety

• MeSH
• antagonisté hormonů farmakologie   MeSH
• benzodiazepinony farmakologie   MeSH
• devazepid farmakologie   MeSH
• fenylmočovinové sloučeniny farmakologie   MeSH
• financování organizované MeSH
• hubenost MeSH
• injekce intraperitoneální MeSH
• injekce intraventrikulární MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neurony metabolismus   účinky léků   MeSH
• nucleus dorsomedialis hypothalami fyziologie   účinky léků   MeSH
• nucleus paraventricularis hypothalami fyziologie   účinky léků   MeSH
• nucleus solitarius fyziologie   účinky léků   MeSH
• pátrací chování fyziologie   účinky léků   MeSH
• peptidové fragmenty farmakologie   MeSH
• proteiny nervové tkáně farmakologie   MeSH
• protoonkogenní proteiny c-fos metabolismus   MeSH
• receptor cholecystokininu A antagonisté a inhibitory   MeSH
• receptor cholecystokininu B antagonisté a inhibitory   MeSH
• regulace chuti k jídlu fyziologie   účinky léků   MeSH
• sinkalid farmakologie   MeSH
• synergismus léků MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

• MeSH
• bariatrická chirurgie MeSH
• experimenty na zvířatech MeSH
• lidé MeSH
• myši MeSH
• obezita terapie   epidemiologie   terapie   MeSH
• peptidové hormony terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH

• Publikační typ
• abstrakty MeSH

CART (cocaine- and amphetamine-regulated transcript) peptides have been studied for ten years. We report specific binding of 125I-CART(61-102) to the rat adrenal pheochromocytoma PC12 cell line, both intact cells and cell membranes. Saturation binding to intact plated cells resulted in Kd of 0.48+/-0.16 nM and Bmax of 2228+/-529 binding sites/cell. 125I-CART(61-102) was also bound to PC12 cells differentiated using nerve growth factor to the neuronal phenotype with non-specific binding below 20%, and Kd of 1.90+/-0.27 nM and Bmax of 11,194+/-261 binding sites/cell. In competitive binding experiments, CART(61-102), CART(55-102) and di-iodinated CART(61-102) were bound to PC12 cell membranes with Ki in low nM range; their affinity to intact non-differentiated and differentiated cells was in low 10(-8) M range. In order to prove that iodination did not eliminate the pharmacological properties of CART, we tested the biological activity of di-iodinated CART(61-102). It decreased food intake in in vivo feeding experiment on fasted mice in a dose of 1 microg/mouse to the same extent as CART(61-102) in a dose of 0.5 microg/mouse.

• MeSH
• biologické modely MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčná membrána metabolismus   MeSH
• buňky PC12 MeSH
• časové faktory MeSH
• fenotyp MeSH
• feochromocytom MeSH
• financování organizované MeSH
• izotopy jodu metabolismus   MeSH
• kinetika MeSH
• krysa rodu rattus MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory nadledvin MeSH
• neurony metabolismus   patologie   MeSH
• neurotrofní faktory farmakologie   MeSH
• peptidové fragmenty metabolismus   MeSH
• přijímání potravy účinky léků   MeSH
• proteiny nervové tkáně farmakologie   metabolismus   MeSH
• radioizotopy jodu metabolismus   MeSH
• vazba proteinů MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH