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Dollada Srisai, Terry C Yin, Abigail A Lee, Alix A J Rouault, Nicole A Pearson, Justin L Grobe, Julien A Sebag
Ghrelin is the only known circulating orexigenic hormone. It is primarily secreted by the stomach and acts at its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), in the hypothalamus to signal hunger and promote food intake. The melanocortin receptor accessory protein 2 (MRAP2) was previously shown to regulate energy homeostasis through the modulation of the activity of the melanocortin-4 receptor and prokineticin receptors. In this study we identify MRAP2 as a partner of ghrelin-GHSR1a signaling...
September 28, 2017: Nature Communications
Fantao Meng, Yong Han, Dollada Srisai, Valery Belakhov, Monica Farias, Yong Xu, Richard D Palmiter, Timor Baasov, Qi Wu
Currently available inducible Cre/loxP systems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed from nsCre transgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides...
March 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
Anna L Chaly, Dollada Srisai, Ellen E Gardner, Julien A Sebag
The Melanocortin Receptor Accessory Protein 2 (MRAP2) is an important regulator of energy homeostasis and its loss causes severe obesity in rodents. MRAP2 mediates its action in part through the potentiation of the MC4R, however, it is clear that MRAP2 is expressed in tissues that do not express MC4R, and that the deletion of MRAP2 does not recapitulate the phenotype of Mc4r KO mice. Consequently, we hypothesized that other GPCRs involved in the control of energy homeostasis are likely to be regulated by MRAP2...
February 1, 2016: ELife
Qi Wu, Ruimao Zheng, Dollada Srisai, G Stanley McKnight, Richard D Palmiter
Diphtheria toxin-mediated, acute ablation of hypothalamic neurons expressing agouti-related protein (AgRP) in adult mice leads to anorexia and starvation within 7 d that is caused by hyperactivity of neurons within the parabrachial nucleus (PBN). Because NMDA glutamate receptors are involved in various synaptic plasticity-based behavioral modifications, we hypothesized that modulation of the NR2A and NR2B subunits of the NMDA receptor in PBN neurons could contribute to the anorexia phenotype. We observed by Western blot analyses that ablation of AgRP neurons results in enhanced expression of NR2B along with a modest suppression of NR2A...
September 3, 2013: Proceedings of the National Academy of Sciences of the United States of America
Dollada Srisai, Matthew P Gillum, Brandon L Panaro, Xian-Man Zhang, Naiphinich Kotchabhakdi, Gerald I Shulman, Kate L J Ellacott, Roger D Cone
Defective melanocortin signaling causes hyperphagic obesity in humans and the melanocortin-4 receptor knockout mouse (MC4R(-/-)). The human disease most commonly presents, however, as haploinsufficiency of the MC4R. This study validates the MC4R(+/-) mouse as a model of the human disease in that, like the MC4R(-/-), the MC4R(+/-) mouse also exhibits a sustained hyperphagic response to dietary fat. Furthermore, both saturated and monounsaturated fats elicit this response. N-acylphosphatidylethanolamine (NAPE) is a signaling lipid induced after several hours of high-fat feeding, that, if dysregulated, might explain the feeding behavior in melanocortin obesity syndrome...
March 2011: Endocrinology
Masoud Ghamari-Langroudi, Dollada Srisai, Roger D Cone
Melanocortin-4 receptor (MC4R) is critical for energy homeostasis, and the paraventricular nucleus of the hypothalamus (PVN) is a key site of MC4R action. Most studies suggest that leptin regulates PVN neurons indirectly, by binding to receptors in the arcuate nucleus or ventromedial hypothalamus and regulating release of products like α-melanocyte-stimulating hormone (α-MSH), neuropeptide Y (NPY), glutamate, and GABA from first-order neurons onto the MC4R PVN cells. Here, we investigate mechanisms underlying regulation of activity of these neurons under various metabolic states by using hypothalamic slices from a transgenic MC4R-GFP mouse to record directly from MC4R neurons...
January 4, 2011: Proceedings of the National Academy of Sciences of the United States of America
Masoud Ghamari-Langroudi, Kristen R Vella, Dollada Srisai, Michelle L Sugrue, Anthony N Hollenberg, Roger D Cone
Fasting-induced suppression of thyroid hormone levels is an adaptive response to reduce energy expenditure in both humans and mice. This suppression is mediated by the hypothalamic-pituitary-thyroid axis through a reduction in TRH levels expressed in neurons of the paraventricular nucleus of the hypothalamus (PVN). TRH gene expression is positively regulated by leptin. Whereas decreased leptin levels during fasting lead to a reduction in TRH gene expression, the mechanisms underlying this process are still unclear...
December 2010: Molecular Endocrinology
N Voraphani, A Theamboonlers, A Khongphatthanayothin, C Srisai, Y Poovorawan
BACKGROUND: Evidence of hepatocellular damage is common in dengue-infected individuals. Hepatocyte growth factor (HGF), a key cytokine responsible for liver regeneration, may play a prognostic role in dengue virus infection. AIM: To determine the relationship between serum HGF level and disease severity in patients with dengue virus infection. METHODS: Serum samples from 27 children [17 dengue fever (DF), ten dengue haemorrhagic fever (DHF)] with serologically confirmed dengue virus infection during the febrile, toxic stages and at follow-up were analysed for HGF...
2010: Annals of Tropical Paediatrics
Patcharapa Sathupan, Apichai Khongphattanayothin, Jirabat Srisai, Karakade Srikaew, Yong Poovorawan
UNLABELLED: Increased vascular permeability is the main aetiology for hypovolaemic shock and circulatory failure in dengue haemorrhagic fever (DHF). AIM: To investigate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of DHF. METHODS: Serum samples from 41 patients [15 dengue fever (DF), 26 DHF] with serologically confirmed dengue virus infection during the febrile, toxic, convalescent stages and at follow-up were analysed for VEGF...
September 2007: Annals of Tropical Paediatrics
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