RESUMO
BACKGROUND AND AIMS: Growing evidence suggests maternal obesity leads to adverse outcomes for offspring, including increased cardiovascular disease (CVD). Alterations in taste preferences of offspring from mothers consuming a high fat diet (HFD) have also been reported. Given recent reports describing cardiac taste receptors, we examined whether the expression of umami and bitter taste receptors is modulated by maternal obesity, and compared this with the physiological challenge of maternal exercise. METHODS AND RESULTS: Female Sprague-Dawley rats were fed chow (C) or HFD (F) and half of each were provided with a running wheel to enable voluntary exercise (CE or FE), the others remaining sedentary (CS or FS). Two pups from each mother were killed at postnatal day 19. Both lean and obese dams undertook similar amounts of exercise (8.1 ± 2.4 vs 5.1 ± 1.5 km). Maternal obesity increased offspring body weight, adiposity, net and weight-corrected heart ventricle weight, with no effect of exercise. Maternal obesity also increased offspring plasma leptin concentrations, which were normalised by maternal exercise. Cardiac ventricle mRNA expression of bitter taste receptors, ß-adrenoceptor (Adrbk1) and angiotensin II receptor type 1a (Agtr1a) were significantly decreased in response to maternal obesity, with maternal exercise decreasing Agtr1a in FE offspring. No changes in umami receptors were observed. FTO mRNA expression was down-regulated by maternal HFD with an up-regulation in offspring of CE mothers. CONCLUSION: Maternal obesity affected the expression of bitter taste receptors and other genes in the heart ventricle, potentially implicating these genes in the development of CVD associated with maternal obesity.
Assuntos
Expressão Gênica , Ventrículos do Coração/metabolismo , Proteínas/genética , Adiposidade/fisiologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Animais , Peso Corporal , Dieta , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo , Feminino , Leptina/sangue , Fenômenos Fisiológicos da Nutrição Materna , Obesidade , Condicionamento Físico Animal , Gravidez , Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Regulação para CimaRESUMO
The pharmacokinetics and urinary excretion of gatifloxacin were investigated after a single intravenous injection of 4 mg/kg body weight in buffalo calves. The therapeutic plasma drug concentration was maintained for up to 12 h. Gatifloxacin rapidly distributed from blood to tissue compartments, which was evident from the high values of the distribution rate constant, alpha1 (11.1 +/- 1.06 h(-1)) and the rate constant of transfer of drug from central to peripheral compartment, k12 (6.29 +/- 0.46 h(-1)). The area under the plasma drug concentration-time curve and apparent volume of distribution were 17.1 +/- 0.63 (microg.h)/ml and 3.56 +/- 0.95 L/kg, respectively. The elimination half-life (t (1/2 beta)), total body clearance (ClB) and the ratio of drug present in tissues and plasma (T/P) were 10.4 +/- 2.47 h, 235.1 +/- 8.47 ml/(kg.h) and 10.1 +/- 2.25, respectively. About 19.7% of the administered drug was excreted in urine within 24 h. A satisfactory intravenous dosage regimen for gatifloxacin in buffalo calves would be 5.3 mg/kg at 24 h intervals.
