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dc.contributor.authorNisr, RB
dc.contributor.authorAffourtit, C
dc.date.accessioned2016-05-06T07:48:40Z
dc.date.available2016-05-06T07:48:40Z
dc.date.issued2016-09-01
dc.identifier.issn0005-2728
dc.identifier.issn0006-3002
dc.identifier.urihttp://hdl.handle.net/10026.1/4585
dc.description.abstract

Mitochondrial dysfunction has been associated with obesity-related muscle insulin resistance, but the causality of this association is controversial. The notion that mitochondrial oxidative capacity may be insufficient to deal appropriately with excessive nutrient loads is for example disputed. Effective mitochondrial capacity is indirectly, but largely determined by ATP-consuming processes because skeletal muscle energy metabolism is mostly controlled by ATP demand. Probing the bioenergetics of rat and human myoblasts in real time we show here that the saturated fatty acid palmitate lowers the rate and coupling efficiency of oxidative phosphorylation under conditions it causes insulin resistance. Stearate affects the bioenergetic parameters similarly, whereas oleate and linoleate tend to decrease the rate but not the efficiency of ATP synthesis. Importantly, we reveal that palmitate influences how oxidative ATP supply is used to fuel ATP-consuming processes. Direct measurement of newly made protein demonstrates that palmitate lowers the rate of de novo protein synthesis by more than 30%. The anticipated decrease of energy demand linked to protein synthesis is confirmed by attenuated cycloheximide-sensitivity of mitochondrial respiratory activity used to make ATP. This indirect measure of ATP turnover indicates that palmitate lowers ATP supply reserved for protein synthesis by at least 40%. This decrease is also provoked by stearate, oleate and linoleate, albeit to a lesser extent. Moreover, palmitate lowers ATP supply for sodium pump activity by 60-70% and, in human cells, decreases ATP supply for DNA/RNA synthesis by almost three-quarters. These novel fatty acid effects on energy expenditure inform the 'mitochondrial insufficiency' debate.

dc.format.extent1403-1411
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoen
dc.publisherElsevier BV
dc.subjectPalmitate-induced insulin resistance
dc.subjectSkeletal muscle
dc.subjectMitochondrial dysfunction
dc.subjectATP turnover
dc.subjectObesity
dc.subjectType 2 diabetes
dc.titlePalmitate-induced changes in energy demand cause reallocation of ATP supply in rat and human skeletal muscle cells
dc.typejournal-article
dc.typeArticle
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/27154056
plymouth.issue9
plymouth.volume1857
plymouth.publisher-urlhttp://dx.doi.org/10.1016/j.bbabio.2016.04.286
plymouth.publication-statusPublished
plymouth.journalBBA Bioenergetics
dc.identifier.doi10.1016/j.bbabio.2016.04.286
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeNetherlands
dcterms.dateAccepted2016-04-28
dc.rights.embargodate2017-5-3
dc.identifier.eissn0006-3002
dc.rights.embargoperiodNo embargo
rioxxterms.versionofrecord10.1016/j.bbabio.2016.04.286
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-09-01
rioxxterms.typeJournal Article/Review
plymouth.funderWhy do pancreatic beta cells waste energy?::MRC


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