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1000 Titel
  • Central Acting Hsp10 Regulates Mitochondrial Function, Fatty Acid Metabolism, and Insulin Sensitivity in the Hypothalamus
1000 Autor/in
  1. Wardelmann, Kristina |
  2. Rath, Michaela |
  3. Castro, José P. |
  4. Blümel, Sabine |
  5. Schell, Mareike |
  6. Hauffe, Robert |
  7. Schumacher, Fabian |
  8. Flore, Tanina |
  9. Ritter, Katrin |
  10. Wernitz, Andreas |
  11. Hosoi, Toru |
  12. Ozawa, Koichiro |
  13. Kleuser, Burkhard |
  14. Weiß, Jürgen |
  15. Schurmann, Annette |
  16. Kleinridders, André |
1000 Erscheinungsjahr 2021
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-04-30
1000 Erschienen in
1000 Quellenangabe
  • 10(5):711
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3390/antiox10050711 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145035/ |
1000 Ergänzendes Material
  • https://www.mdpi.com/2076-3921/10/5/711#supplementary |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling. Although insulin activates this response and improves metabolism, the metabolic impact of one of its members, the mitochondrial chaperone heat shock protein 10 (Hsp10), is unknown. Thus, we hypothesized that a reduction of Hsp10 in hypothalamic neurons will impair mitochondrial function and impact brain insulin action. Therefore, we investigated the role of chaperone Hsp10 by introducing a lentiviral-mediated Hsp10 knockdown (KD) in the hypothalamic cell line CLU-183 and in the arcuate nucleus (ARC) of C57BL/6N male mice. We analyzed mitochondrial function and insulin signaling utilizing qPCR, Western blot, XF96 Analyzer, immunohistochemistry, and microscopy techniques. We show that Hsp10 expression is reduced in T2D mice brains and regulated by leptin in vitro. Hsp10 KD in hypothalamic cells induced mitochondrial dysfunction with altered fatty acid metabolism and increased mitochondria-specific oxidative stress resulting in neuronal insulin resistance. Consequently, the reduction of Hsp10 in the ARC of C57BL/6N mice caused hypothalamic insulin resistance with acute liver insulin resistance.
1000 Sacherschließung
lokal mitochondria
lokal oxidative stress
lokal brain insulin signaling
lokal fatty acid metabolism
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/V2FyZGVsbWFubiwgS3Jpc3RpbmE=|https://orcid.org/0000-0002-5766-0697|https://frl.publisso.de/adhoc/uri/Q2FzdHJvLCBKb3PDqSBQLg==|https://frl.publisso.de/adhoc/uri/QmzDvG1lbCwgU2FiaW5l|https://frl.publisso.de/adhoc/uri/U2NoZWxsLCBNYXJlaWtl|https://orcid.org/0000-0003-3403-6573|https://orcid.org/0000-0001-8703-3275|https://frl.publisso.de/adhoc/uri/RmxvcmUsIFRhbmluYQ==|https://frl.publisso.de/adhoc/uri/Uml0dGVyLCBLYXRyaW4=|https://frl.publisso.de/adhoc/uri/V2Vybml0eiwgQW5kcmVhcw==|https://frl.publisso.de/adhoc/uri/SG9zb2ksIFRvcnU=|https://frl.publisso.de/adhoc/uri/T3phd2EsIEtvaWNoaXJv|https://orcid.org/0000-0002-1888-9595|https://frl.publisso.de/adhoc/uri/V2Vpw58sIErDvHJnZW4=|https://orcid.org/0000-0002-4113-4377|https://frl.publisso.de/adhoc/uri/S2xlaW5yaWRkZXJzLCBBbmRyw6k=
1000 (Academic) Editor
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Bundesministerium für Bildung und Forschung |
  3. State of Brandenburg |
1000 Fördernummer
  1. KL 2399/4-1
  2. -
  3. 82DZD00302
1000 Förderprogramm
  1. -
  2. -
  3. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer KL 2399/4-1
  2. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer State of Brandenburg |
    1000 Förderprogramm -
    1000 Fördernummer 82DZD00302
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6427760.rdf
1000 Erstellt am 2021-05-28T07:23:31.922+0200
1000 Erstellt von 25
1000 beschreibt frl:6427760
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet 2021-05-28T07:44:37.205+0200
1000 Objekt bearb. Fri May 28 07:44:36 CEST 2021
1000 Vgl. frl:6427760
1000 Oai Id
  1. oai:frl.publisso.de:frl:6427760 |
1000 Sichtbarkeit Metadaten public
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