Ablation of Neurons Expressing Melanin-Concentrating Hormone (MCH) in Adult Mice Improves Glucose Tolerance Independent of MCH Signaling
JOURNAL OF NEUROSCIENCE
Authors: Whiddon, Benjamin B.; Palmiter, Richard D.
Abstract
Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine-amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo, we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH (Pmch). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch(DTR/+) mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.
Extent and characteristics of immune infiltration in clear cell renal cell carcinoma and the prognostic value
TRANSLATIONAL ANDROLOGY AND UROLOGY
Authors: Wang, Yuhao; Yang, Jie; Zhang, Qijie; Xia, Jiadong; Wang, Zengjun
Abstract
Background: Immune infiltration has an important impact on the development of clear cell renal cell carcinoma (ccRCC). This article aims to investigate the association between immune infiltration and the clinical features as well as prognosis of clear cell renal cell carcinoma. Methods: Analyze the immune infiltration in ccRCC by applying ESTIMATE and CIBERSORT methods on basic of dataset in TCGA and GEO. And identify the kind of immune cell and genes that may play the central role. Results: High Immune score and high property of T-regs are both significantly associated with the poor OS, high stage and more chances of metastases in ccRCC. CXCL-1, SAA1, PMCH, CCL-5 are all significantly negatively correlated to OS and positively correlated to stage and chance of metastases in ccRCC. High property of T- regs, CXCL-1 and SAA1 are also significantly associated with high Fuhrman grade while PMCH and CCL5 not. Conclusions: Immune infiltration in RCC has a negative influence on ccRCC and T-regs may play a vital role in this process mediated by CXCL-1 or SSA1.