气候变化领域集成服务门户(CCPortal): Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity

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DOI	10.1038/s41467-021-25380-2
	Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity
	Xiao X.; Yeghiazaryan G.; Hess S.; Klemm P.; Sieben A.; Kleinridders A.; Morgan D.A.; Wunderlich F.T.; Rahmouni K.; Kong D.; Scammell T.E.; Lowell B.B.; Kloppenburg P.; Brüning J.C.; Hausen A.C.
发表日期	2021
ISSN	2041-1723
卷号	12 期号:1
英文摘要	The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis. © 2021, The Author(s).
语种	英语
scopus关键词	orexin 1 receptor; orexin 2 receptor; serotonin transporter; glucose; Hcrtr1 protein, mouse; Hcrtr2 protein, mouse; orexin; orexin receptor; serotonin transporter; cell; glucose; metabolism; obesity; peptide; animal experiment; animal model; animal tissue; Article; brown adipose tissue; controlled study; diet-induced obesity; dorsal raphe nucleus; gene activation; gluconeogenesis; glucose homeostasis; glucose metabolism; glucose tolerance; glucose transport; glucose utilization; insulin sensitivity; insulin signaling; lateral hypothalamus; male; median raphe nucleus; metabolic regulation; mouse; nonhuman; nucleus raphe pallidus; optogenetics; protein expression; serotoninergic nerve cell; skeletal muscle; adverse event; animal; cytology; genetics; homeostasis; insulin resistance; lipid diet; liver; metabolism; nerve fiber; obesity; raphe nucleus; serotoninergic nerve cell; signal transduction; Adipose Tissue, Brown; Animals; Diet, High-Fat; Glucose; Homeostasis; Hypothalamic Area, Lateral; Insulin Resistance; Liver; Mice; Nerve Fibers; Obesity; Orexin Receptors; Orexins; Raphe Nuclei; Serotonergic Neurons; Serotonin Plasma Membrane Transport Proteins; Signal Transduction
来源期刊	Nature Communications
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250625
作者单位	Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; National Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Neuroscience and Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, IA, United States; Division of Endocrinology, Department of Pediatrics, F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA, United States; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States; Department of Neurolo...
推荐引用方式 GB/T 7714	Xiao X.,Yeghiazaryan G.,Hess S.,et al. Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity[J],2021,12(1).
APA	Xiao X..,Yeghiazaryan G..,Hess S..,Klemm P..,Sieben A..,...&Hausen A.C..(2021).Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity.Nature Communications,12(1).
MLA	Xiao X.,et al."Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity".Nature Communications 12.1(2021).