Show simple item record

dc.contributor.authorYang, Xiuying
dc.contributor.authorNoh, Hye Lim
dc.contributor.authorSaengnipanthkul, Suchaorn
dc.contributor.authorKim, Jason K.
dc.contributor.authorLee, Chi Wai
dc.contributor.authorChan, Chi Bun
dc.date2022-08-11T08:10:18.000
dc.date.accessioned2022-08-23T17:03:19Z
dc.date.available2022-08-23T17:03:19Z
dc.date.issued2019-08-13
dc.date.submitted2019-10-07
dc.identifier.citation<p>Sci Signal. 2019 Aug 13;12(594). pii: eaau1468. doi: 10.1126/scisignal.aau1468. <a href="https://doi.org/10.1126/scisignal.aau1468">Link to article on publisher's site</a></p>
dc.identifier.issn1945-0877 (Linking)
dc.identifier.doi10.1126/scisignal.aau1468
dc.identifier.pmid31409756
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44399
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
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-1alpha 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31409756&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1126/scisignal.aau1468
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectBiochemistry
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular Biology
dc.subjectMusculoskeletal System
dc.titleMuscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility
dc.typeJournal Article
dc.source.journaltitleScience signaling
dc.source.volume12
dc.source.issue594
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pmm_pp/133
dc.identifier.contextkey15503634
html.description.abstract<p>The 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-1alpha 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.</p>
dc.identifier.submissionpathpmm_pp/133
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pageseaau1468


This item appears in the following Collection(s)

Show simple item record