natriuretic-peptide--c-type and Weight-Gain

Cyclic GMP (cGMP) is an important intracellular regulator of endochondral bone growth and skeletal remodeling. Tadalafil, an inhibitor of the phosphodiesterase (PDE) type 5 (PDE5) that specifically hydrolyzes cGMP, is increasingly used to treat children with pulmonary arterial hypertension (PAH), but the effect of tadalafil on bone growth and strength has not been previously investigated. In this study, we first analyzed the expression of transcripts encoding PDEs in primary cultures of chondrocytes from newborn rat epiphyses. We detected robust expression of PDE5 as the major phosphodiesterase hydrolyzing cGMP. Time-course experiments showed that C-type natriuretic peptide increased intracellular levels of cGMP in primary chondrocytes with a peak at 2 min, and in the presence of tadalafil the peak level of intracellular cGMP was 37% greater ( P < 0.01) and the decline was significantly attenuated. Next, we treated 1-mo-old Sprague Dawley rats with vehicle or tadalafil for 3 wk. Although 10 mg·kg

Topics: Animals; Animals, Newborn; Bone and Bones; Bone Development; Cancellous Bone; Chondrocytes; Cortical Bone; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Epiphyses; Male; Natriuretic Peptide, C-Type; Phosphodiesterase 5 Inhibitors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tadalafil; Weight Gain; X-Ray Microtomography

C-type natriuretic peptide (CNP) and its receptor, natriuretic peptide receptor-B (NPR-B), are abundantly distributed in the hypothalamus. To explore the role of central CNP/NPR-B signaling in energy regulation, we generated mice with brain-specific NPR-B deletion (BND mice) by crossing Nestin-Cre transgenic mice and mice with a loxP-flanked NPR-B locus. Brain-specific NPR-B deletion prevented body weight gain induced by a high-fat diet (HFD), and the mesenteric fat and liver weights were significantly decreased in BND mice fed an HFD. The decreased liver weight in BND mice was attributed to decreased lipid accumulation in the liver, which was confirmed by histologic findings and lipid content. Gene expression analysis revealed a significant decrease in the mRNA expression levels of CD36, Fsp27, and Mogat1 in the liver of BND mice, and uncoupling protein 2 mRNA expression was significantly lower in the mesenteric fat of BND mice fed an HFD than in that of control mice. This difference was not observed in the epididymal or subcutaneous fat. Although previous studies reported that CNP/NPR-B signaling inhibits SNS activity in rodents, SNS is unlikely to be the underlying mechanism of the metabolic phenotype observed in BND mice. Taken together, CNP/NPR-B signaling in the brain could be a central factor that regulates visceral lipid accumulation and hepatic steatosis under HFD conditions. Further analyses of the precise mechanisms will enhance our understanding of the contribution of the CNP/NPR-B system to energy regulation.

Topics: Acyltransferases; Animals; Brain; CD36 Antigens; Diet, High-Fat; Energy Metabolism; Fatty Liver; Gene Deletion; Gene Expression Profiling; Hypothalamus; Intra-Abdominal Fat; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Natriuretic Peptide, C-Type; Obesity; Organ Size; Proteins; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Signal Transduction; Weight Gain

To determine the incidence of and risk factors for exercise-associated hyponatremia (EAH) in cyclists completing a long-distance bike ride and to assess whether postexercise serum NT-proBNP concentration (brain natriuretic protein precursor) differed between riders with and without EAH.. Observational study.. "Around the Bay in a Day" cycle event, October 2010.. One hundred thirty-nine cyclists prospectively enrolled, with 90 completing 210 or 250 km.. Body weight change and fluid intake during the event, and postevent serum sodium concentration ([Na+]) and NT-proBNP concentration ([NT-proBNP]).. Four riders (4.5%) were hyponatremic ([Na+] < 135 mmol/L). The lowest postride [Na+] was 126 mmol/L. Hyponatremia was associated with a mean weight gain of 3.4 kg (3.9% of total body weight). Significant negative correlations were found between postride [Na+] and change in weight (r = -0.34; P < 0.01) and fluid intake when expressed as total volume (r = -0.35; P < 0.01), mL/kg body weight (r = 0.33; P < 0.01), mL·kg·h (r = -0.27; P < 0.01), or mL/h (r = -0.29; P < 0.01). NT-proBNP concentrations levels in 3 of the 4 hyponatremic subjects were markedly elevated compared with eunatremic subjects matched for age, sex, distance ridden, training, and medical history.. Exercise-associated hyponatremia was found to occur in 4.5% of the study group and was associated with weight gain during a prolonged bike ride. Postride [Na+] varied inversely with weight change and with fluid intake. Three of 4 hyponatremic riders had significant elevations of [NT-proBNP]. These results support the hypothesis that overconsumption of hypotonic fluids in this setting is the most important cause of EAH.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bicycling; Drinking; Female; Humans; Hyponatremia; Incidence; Male; Middle Aged; Natriuretic Peptide, C-Type; Prospective Studies; Risk Factors; Sodium; Weight Gain; Young Adult