METABOLISM: Keeping food consumption under control, a new role for the protein PrP
Tatsushi Onaka and colleagues, at Jichi Medical University, Japan, have provided new insight into the network of signals that emanate from the gut and the brainstem of rodents to regulate food intake.
In the study, neurons in the region of the rat brainstem known as the nucleus tractus solitarii that express the protein prolactin-releasing peptide (PrP) were found to be activated following food intake. Consistent with PrP functioning as a satiety signal (a signal that suppresses food intake), mice lacking PrP became obese in adulthood as a result of increased food intake and decreased responsiveness to other satiety signals. Similarly, obesity as a result of increased food intake was observed in rats in which an antibody that blocks PrP was administered directly into the brain. In both cases the increased food intake was reflected by an increase in meal size. Thus, PrRP acts as a satiety signal in the brain of rodents, and disruption of this important signal can cause obesity.
TITLE: Endogenous prolactin-releasing peptide regulates food intake in rodents
AUTHOR CONTACT:Tatsushi OnakaJichi Medical University, Shimotsuke, Tochigi, Japan.Phone: 81-285-58-7318; Fax: 81-285-44-8147; E-mail: tonaka@jichi.ac.jp.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34682
CARDIOLOGY: The protein FHL1 helps heart muscle cells respond to high pressure
High blood pressure puts stress on the heart, which responds by increasing in size, a process known as cardiac hypertrophy. This is a leading cause of heart failure and understanding the molecular pathways involved is important for identifying potential therapeutic targets. New data, generated in mice by Ju Chen and colleagues, at the University of California, San Diego, La Jolla, have now identified the protein FHL1 as part of the complex in heart muscle cells (cardiomyocytes) that senses the high pressure–induced stress that triggers cardiac hypertrophy. Specifically, cardiac hypertrophy triggered by experimentally induced high blood pressure was markedly diminished in mice lacking FHL1. Further analysis shed light on other important molecules and signaling pathways involved in the process of sensing high pressure–induced cardiac stress, leading the authors to suggest that further analysis of these might reveal a new target for drugs to treat heart disease characterized by cardiac hypertrophy.
TITLE: An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice
AUTHOR CONTACT:Ju ChenUniversity of California, San Diego, La Jolla, California, USA.Phone: (858) 822-4276; Fax: (858) 822-1355; E-mail: juchen@ucsd.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34472
VASCULAR BIOLOGY: A new regulator of blood vessel formation: the protein AIP1
AIP1 is a recently identified protein known to be highly expressed in the cells that line blood vessels (endothelial cells) and to regulate the death (by a process known as apoptosis) of these cells in vitro . However, the in vivo function of AIP1 in endothelial cells has not been determined. But now, Wang Min, Hong Chen, and colleagues, at Yale University Medical School, New Haven, have generated mice lacking AIP1 and found that AIP1 regulates new blood vessel formation (angiogenesis) under inflammatory conditions.
In the study, AIP1-deficient mice exhibited markedly enhanced angiogenesis in two models of inflammatory angiogenesis. In one model this was associated with increased VEGF-VEGFR2 signaling. Further analysis determined the mechanism by which AIP1 regulates angiogenesis under inflammatory conditions: AIP1 is recruited to VEGFR2 signaling complexes formed after VEGF binds VEGFR2 and that AIP1 inhibits VEGFR2 signaling, leading to decreased endothelial cell migration and therefore decreased angiogenesis.
TITLE: AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice
AUTHOR CONTACT:Wang MinYale University School of Medicine, New Haven, Connecticut, USA.Phone: (203) 785-6047; Fax: (203) 737-2293; E-mail: wang.min@yale.edu.
Hong ChenOklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.Phone: (405) 271-2750; Fax: (405) 271-3137; E-mail: hong-chen@omrf.org.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36168