Nature communications, 2021-09, Vol.12 (1), p.5249-5249, Article 5249
2021
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- Autor(en) / Beteiligte
- Titel
- Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity
- Ist Teil von
- Nature communications, 2021-09, Vol.12 (1), p.5249-5249, Article 5249
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-25380-2Titel-ID: cdi_doaj_primary_oai_doaj_org_article_526ad1da292b4e9a9a66f3e0635380a6
- Format
- –
- Schlagworte
- Adipose tissue, Adipose tissue (brown), Adipose Tissue, Brown - metabolism, Animals, Deactivation, Diet, Diet, High-Fat - adverse effects, Dorsal raphe nucleus, Fibers, Gluconeogenesis, Glucose, Glucose - metabolism, Glucose tolerance, Homeostasis, Hypothalamic Area, Lateral - cytology, Hypothalamic Area, Lateral - metabolism, Hypothalamus, Hypothalamus (lateral), Inactivation, Insulin, Insulin Resistance, Liver - metabolism, Mice, Muscles, Nerve Fibers - metabolism, Neurons, Obesity, Obesity - etiology, Obesity - metabolism, Orexin receptors, Orexin Receptors - genetics, Orexin Receptors - metabolism, Orexins, Orexins - metabolism, Raphe nuclei, Raphe Nuclei - metabolism, Receptors, Sensitivity, Serotonergic Neurons - metabolism, Serotonin, Serotonin Plasma Membrane Transport Proteins - genetics, Serotonin Plasma Membrane Transport Proteins - metabolism, Serotonin transporter, Signal Transduction, Skeletal muscle