Xiao, Xing, Yeghiazaryan, Gagik, Hess, Simon, Klemm, Paul ORCID: 0000-0002-5985-1737, Sieben, Anna, Kleinridders, Andre ORCID: 0000-0002-4248-6366, Morgan, Donald A., Wunderlich, F. Thomas, Rahmouni, Kamal, Kong, Dong, Scammell, Thomas E., Lowell, Bradford B., Kloppenburg, Peter, Bruning, Jens C. and Hausen, A. Christine (2021). Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity. Nat. Commun., 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

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. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Xiao, XingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yeghiazaryan, GagikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klemm, PaulUNSPECIFIEDorcid.org/0000-0002-5985-1737UNSPECIFIED
Sieben, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleinridders, AndreUNSPECIFIEDorcid.org/0000-0002-4248-6366UNSPECIFIED
Morgan, Donald A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahmouni, KamalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kong, DongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scammell, Thomas E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lowell, Bradford B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruning, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hausen, A. ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-597449
DOI: 10.1038/s41467-021-25380-2
Journal or Publication Title: Nat. Commun.
Volume: 12
Number: 1
Date: 2021
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BROWN-ADIPOSE-TISSUE; DORSAL RAPHE NUCLEUS; PROTEIN DISTRIBUTION; CEREBROSPINAL-FLUID; ENERGY HOMEOSTASIS; INSULIN-RESISTANCE; SKELETAL-MUSCLE; GENE-EXPRESSION; NERVOUS-SYSTEM; BRAIN-SLICESMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59744

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