التفاصيل البيبلوغرافية
| العنوان: |
Ptp1b deletion in pro-opiomelanocortin neurons increases energy expenditure and impairs endothelial function via TNF-α dependent mechanisms. |
| المؤلفون: |
Bruder-Nascimento, Thiago, Kennard, Simone, Antonova, Galina, Mintz, James D., Bence, Kendra K., de Chantemèle, Eric J. Belin |
| المصدر: |
Clinical Science; Jun2016, Vol. 130 Issue 11, p881-893, 13p |
| مصطلحات موضوعية: |
PROTEIN-tyrosine phosphatase, ENDOTHELIAL cells, TUMOR necrosis factors, INFLAMMATION, MELANOCORTIN receptors, DELETION mutation, OBESITY |
| مستخلص: |
Aims: Protein tyrosine phosphatase 1b (Ptp1b) is a negative regulator of leptin and insulin-signaling pathways. Its targeted deletion in proopiomelanocortin (POMC) neurons protects mice from obesity and diabetes by increasing energy expenditure. Inflammation accompanies increased energy expenditure. Therefore, this study aimed to determine whether POMC-Ptp1b deletion increases energy expenditure via an inflammatory process, which would impair endothelial function. Methods and Results: We characterized the metabolic and cardiovascular phenotypes of Ptp1b+/+ and POMC-Ptp1b-/- mice. Clamp studies revealed that POMC-Ptp1b deletion reduced body fat and increased energy expenditure as evidenced by a decrease in feed efficiency and an increase in oxygen consumption and respiratory exchange ratio. POMC-Ptp1b deletion induced a 2.5 fold increase in plasma TNF-α levels and elevated body temperature. Vascular studies revealed an endothelial dysfunction in POMC-Ptp1b-/-. Nitric oxide synthase inhibition (L-NAME) reduced relaxation to a similar extent in Ptp1b+/+ and POMC-Ptp1b-/-. POMC-Ptp1b deletion decreased ROS-scavenging enzymes (SODs) while it increased ROS-generating enzymes (NOxs) and cyclooxygenase-2 expression, in aorta. ROS scavenging or NADPH oxidase inhibition only partially improved relaxation while COX-2 inhibition and thromboxane-A2 antagonism fully restored relaxation in POMC-Ptp1b-/-. Chronic treatment with the soluble TNF-α receptor etanercept decreased body temperature, restored endothelial function and reestablished aortic COX-2, NOXs and SOD expression to their baseline levels in POMC-Ptp1b-/-. However, etanercept promoted body weight gain and decreased energy expenditure in POMC-Ptp1b-/- mice. Conclusion: POMC-Ptp1b deletion increases plasma TNF-α levels, which contribute to body weight regulation via increased energy expenditure and impair endothelial function via COX-2 and ROS-dependent mechanisms. [ABSTRACT FROM AUTHOR] |
|
Copyright of Clinical Science is the property of Portland Press Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
