Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity
| العنوان: | Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity |
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| المؤلفون: | Anna Sieben, F. Thomas Wunderlich, Dong Kong, Xing Xiao, Peter Kloppenburg, André Kleinridders, Thomas E. Scammell, Gagik Yeghiazaryan, Simon Hess, A. Christine Hausen, Paul Klemm, Bradford B. Lowell, Jens C. Brüning, Kamal Rahmouni, Donald A. Morgan |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-20 (2021) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Blood Glucose, medicine.medical_specialty, Median raphe nucleus, Lateral hypothalamus, Science, General Physics and Astronomy, Diet, High-Fat, Serotonergic, Neural circuits, General Biochemistry, Genetics and Molecular Biology, Article, Mice, Nerve Fibers, Dorsal raphe nucleus, Adipose Tissue, Brown, Orexin Receptors, Internal medicine, mental disorders, medicine, Animals, Homeostasis, Glucose homeostasis, Humans, Obesity, Serotonin Plasma Membrane Transport Proteins, Orexins, Multidisciplinary, Raphe, Chemistry, Diabetes, digestive, oral, and skin physiology, General Chemistry, Orexin receptor, Orexin, Glucose, Endocrinology, Liver, nervous system, Hypothalamic Area, Lateral, Raphe Nuclei, Insulin Resistance, Fat metabolism, hormones, hormone substitutes, and hormone antagonists, psychological phenomena and processes, Serotonergic Neurons, Signal Transduction |
| الوصف: | 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. The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here the authors report that inactivation of the orexin receptor type 1 or 2 in serotonergic neurons differentially regulate systemic glucose homeostasis in the context of diet induced obesity. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39018121014cacedc640165017f559f8Test https://doaj.org/article/526ad1da292b4e9a9a66f3e0635380a6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....39018121014cacedc640165017f559f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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