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Diabetologia
Published in: Diabetologia 5/2016

Open Access 01-05-2016 | Article

Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting-induced insulin resistance and lipotoxicity in humans

Authors: Anne Gemmink, Madeleen Bosma, Helma J. H. Kuijpers, Joris Hoeks, Gert Schaart, Marc A. M. J. van Zandvoort, Patrick Schrauwen, Matthijs K. C. Hesselink

Published in: Diabetologia | Issue 5/2016

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Abstract

Aims/hypothesis

In contrast to insulin-resistant individuals, insulin-sensitive athletes possess high intramyocellular lipid content (IMCL), good mitochondrial function and high perilipin 5 (PLIN5) levels, suggesting a role for PLIN5 in benign IMCL storage. We hypothesised a role for PLIN5 in modulating fasting-mediated insulin resistance.

Methods

Twelve men were fasted for 60 h, before and after which muscle biopsies were taken and stained for lipid droplets (LDs), PLIN5 and laminin. Confocal microscopy images were analysed for LD size, number, PLIN5 association and subcellular distribution.

Results

Fasting elevated IMCL content 2.8-fold and reduced insulin sensitivity (by 55%). Individuals with the most prominent increase in IMCL showed the least reduction in insulin sensitivity (r = 0.657; p = 0.028) and mitochondrial function (r = 0.896; p = 0.006). During fasting, PLIN5 gene expression or PLIN5 protein content in muscle homogenates was unaffected, microscopy analyses revealed that the fraction of PLIN5 associated with LDs (PLIN5+) increased significantly (+26%) upon fasting, suggesting PLIN5 redistribution. The significant increase in LD number (+23%) and size (+23%) upon fasting was entirely accounted for by PLIN5+ LDs, not by LDs devoid of PLIN5. Also the association between IMCL storage capacity and insulin resistance and mitochondrial dysfunction was only apparent for PLIN5+ LDs.

Conclusions/interpretation

Fasting results in subcellular redistribution of PLIN5 and promotes the capacity to store excess fat in larger and more numerous PLIN5-decorated LDs. This associates with blunting of fasting-induced insulin resistance and mitochondrial dysfunction, suggesting a role for PLIN5 in the modulation of fasting-mediated lipotoxicity.

Trial registration:

trialregister.nl NTR 2042
Appendix
Available only for authorised users
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Metadata
Title
Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting-induced insulin resistance and lipotoxicity in humans
Authors
Anne Gemmink
Madeleen Bosma
Helma J. H. Kuijpers
Joris Hoeks
Gert Schaart
Marc A. M. J. van Zandvoort
Patrick Schrauwen
Matthijs K. C. Hesselink
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 5/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-3865-z

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