AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner

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dc.contributor.authorPiekarski, Alissaen
dc.contributor.authorNagarajan, Gurueswaren
dc.contributor.authorIshola, Peteren
dc.contributor.authorFlees, Joshuaen
dc.contributor.authorGreene, Elizabeth S.en
dc.contributor.authorKuenzel, Wayne J.en
dc.contributor.authorOhkubo, Takeshien
dc.contributor.authorMaier, Helenaen
dc.contributor.authorBottje, Walter G.en
dc.contributor.authorCline, Mark A.en
dc.contributor.authorDridi, Samien
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2019-10-29T17:26:58Zen
dc.date.available2019-10-29T17:26:58Zen
dc.date.issued2018-05-15en
dc.description.abstractAutophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. Although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. Here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and signal transducer and activator of transcription (Ob-Rb/STAT) pathway, and significantly increases the expression of autophagy-related proteins (Atg3, Atg5, Atg7, beclinl, and LC3B) in chicken hypothalamus, liver, and muscle. Similarly, leptin treatment activates Ob-Rb/STAT pathway and increased the expression of autophagy-related markers in chicken hypothalamic organotypic cultures, muscle (QM7) and hepatocyte (Sim-CEL) cell cultures as well as in Chinese Hamster Ovary (CHO-K1) cells-overexpressmg chicken Ob-Rb and STAT3. To define the downstream mediator(s) of leptin's effects on autophagy, we determined the role of the master energy sensor AMP-activated protein kinase (AMPK). Leptin treatment significantly increased the phosphorylated levels of AMPK alpha 1/2 at Thr172 site in chicken hypothalamus and liver, but not in muscle. Likewise, AMPK alpha 1/2 was activated by leptin in chicken hypothalamic organotypic culture and Sim-CEL, but not in QM7 cells. Blocking AMPK activity by compound C reverses the autophagy-inducing effect of leptin. Together, these findings indicate that AMPK mediates the effect of leptin on chicken autophagy in a tissue-specific manner.en
dc.description.notesThis work was supported by Arkansas Bioscience Institute (ABI) under Grants (# FY2017 and FY2014) to SD and USDA postdoctoral Grant (# 2015-03541) to AP.en
dc.description.sponsorshipArkansas Bioscience Institute (ABI) [FY2017, FY2014]; USDA postdoctoral Grant [2015-03541]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fphys.2018.00541en
dc.identifier.issn1664-042Xen
dc.identifier.other541en
dc.identifier.pmid29867578en
dc.identifier.urihttp://hdl.handle.net/10919/95198en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectleptinen
dc.subjectautophagyen
dc.subjectAMPKen
dc.subjectICV injectionen
dc.subjectcell culturesen
dc.subjectchickensen
dc.titleAMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manneren
dc.title.serialFrontiers in Physiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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