File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility

TitleMuscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility
Authors
Issue Date2019
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://stke.sciencemag.org/
Citation
Science Signaling, 2019, v. 12 n. 594, article no. eaau1468 How to Cite?
AbstractThe ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1α pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance. © 2019 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/275681
ISSN
2020 Impact Factor: 8.192
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, Z-
dc.contributor.authorBrobst, D-
dc.contributor.authorChan, WS-
dc.contributor.authorTse, CL-
dc.contributor.authorHerlea-Pana, O-
dc.contributor.authorAhuja, P-
dc.contributor.authorBi, X-
dc.contributor.authorZaw, AM-
dc.contributor.authorKwong, SW-
dc.contributor.authorJia, W-
dc.contributor.authorZhang, Z-
dc.contributor.authorZhang, N-
dc.contributor.authorChow, SKH-
dc.contributor.authorCheung, WH-
dc.contributor.authorLouie, CYJ-
dc.contributor.authorGriffin, TM-
dc.contributor.authorNong, W-
dc.contributor.authorHui, JHL-
dc.contributor.authorDu, G-
dc.contributor.authorNoh, HL-
dc.contributor.authorSaengnipanthkul, S-
dc.contributor.authorChow, BKC-
dc.contributor.authorKim, JK-
dc.contributor.authorLee, CW-
dc.contributor.authorChan, CB-
dc.date.accessioned2019-09-10T02:47:29Z-
dc.date.available2019-09-10T02:47:29Z-
dc.date.issued2019-
dc.identifier.citationScience Signaling, 2019, v. 12 n. 594, article no. eaau1468-
dc.identifier.issn1945-0877-
dc.identifier.urihttp://hdl.handle.net/10722/275681-
dc.description.abstractThe ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1α pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance. © 2019 The Authors.-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://stke.sciencemag.org/-
dc.relation.ispartofScience Signaling-
dc.rightsScience Signaling. Copyright © American Association for the Advancement of Science.-
dc.rightsThis is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in [Science Journal Title] on [Volume number and date], DOI: [insert DOI number].-
dc.titleMuscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility-
dc.typeArticle-
dc.identifier.emailTse, CL: tsecl@hku.hk-
dc.identifier.emailKwong, SW: zkowng@hku.hk-
dc.identifier.emailLouie, CYJ: jimmyl@hku.hk-
dc.identifier.emailChow, BKC: bkcc@hku.hk-
dc.identifier.emailLee, CW: chiwai.lee@hku.hk-
dc.identifier.emailChan, CB: chancb@hku.hk-
dc.identifier.authorityLouie, CYJ=rp02118-
dc.identifier.authorityChow, BKC=rp00681-
dc.identifier.authorityLee, CW=rp02089-
dc.identifier.authorityChan, CB=rp02140-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/scisignal.aau1468-
dc.identifier.pmid31409756-
dc.identifier.scopuseid_2-s2.0-85071281655-
dc.identifier.hkuros302425-
dc.identifier.volume12-
dc.identifier.issue594-
dc.identifier.spagearticle no. eaau1468-
dc.identifier.epagearticle no. eaau1468-
dc.identifier.isiWOS:000481406900002-
dc.publisher.placeUnited States-
dc.identifier.issnl1945-0877-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats