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dc.contributor.authorDhayal, S.
dc.contributor.authorWelters, Hannah J.
dc.contributor.authorMorgan, Noel G.
dc.identifier.citationDhayal S et al. Differential effects of saturated and unsaturated fatty acids on autophagy in pancreatic β-cells. J Mol Endocrinol. 2019 Nov;63(4):285-296.en_US
dc.description.abstractLong-chain saturated fatty acids are lipotoxic to pancreatic β-cells, whereas most unsaturates are better tolerated and some may even be cytoprotective. Fatty acids alter autophagy in β-cells and there is increasing evidence that such alterations can impact directly on the regulation of viability. Accordingly, we have compared the effects of palmitate (C16:0) and palmitoleate (C16:1) on autophagy in cultured β-cells and human islets. Treatment of BRIN-BD11 β-cells with palmitate led to enhanced autophagic activity, as judged by cleavage of microtubule-associated protein 1 light chain 3-I (LC3-I) and this correlated with a marked loss of cell viability in the cells. In addition, transfection of these cells with an mCherry-YFP-LC3 reporter construct revealed the accumulation of autophagosomes in palmitate-treated cells, indicating an impairment of autophagosome-lysosome fusion. This was also seen upon addition of the vacuolar ATPase inhibitor, bafilomycin A1. Exposure of BRIN-BD11 cells to palmitoleate (C16:1) did not lead directly to changes in autophagic activity or flux, but it antagonised the actions of palmitate. In parallel, palmitoleate also improved the viability of palmitate-treated BRIN-BD11 cells. Equivalent responses were observed in INS-1E cells and in isolated human islets. Taken together, these data suggest that palmitate may cause an impairment of autophagosome-lysosome fusion. These effects were not reproduced by palmitoleate which, instead, antagonised the responses mediated by palmitate suggesting that attenuation of β-cell stress may contribute to the improvement in cell viability caused by the mono-unsaturated fatty acid.en_US
dc.publisherSheridan PubFactoryen_US
dc.rights© 2019 Society for Endocrinology 2019en_US
dc.rightsCC0 1.0 Universal*
dc.subjectER stressen_US
dc.subjectfatty aciden_US
dc.subjectislets of Langerhansen_US
dc.titleDifferential effects of saturated and unsaturated fatty acids on autophagy in pancreatic β-cellsen_US
dc.typeJournal Articleen_US
dc.identifier.journalJournal of Molecular Endocrinologyen_US
dc.description.noteThis article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.en_US
dc.description.fundingThe authors are grateful to Diabetes UK for financial support via project grants 14/0005093 and 15/0005156 (to N G M) and a PhD studentship (14/0005093) to Patricia Thomas. They also thank Dr Jon Lane (University of Bristol) for the kind gift of a dual-fluorescence LC3 reporter construct.en_US
dc.description.admin-noteaccepted version (12 month embargo), submitted versionen_US

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