Skeletal muscle ceramides do not contribute to physical-inactivity-induced insulin resistance

Journal article


Appriou, Zéphyra, Nay, Kevin, Pierre, Nicolas, Saligaut, Dany, Lefeuvre-Orfila, Luz, Martin, Brice, Cavey, Thibault, Ropert, Martine, Loréal, Olivier, Rannou-Bekono, Françoise and Derbré, Frédéric. (2019). Skeletal muscle ceramides do not contribute to physical-inactivity-induced insulin resistance. Applied Physiology, Nutrition and Metabolism. 44(11), pp. 1180 - 1188. https://doi.org/10.1139/apnm-2018-0850
AuthorsAppriou, Zéphyra, Nay, Kevin, Pierre, Nicolas, Saligaut, Dany, Lefeuvre-Orfila, Luz, Martin, Brice, Cavey, Thibault, Ropert, Martine, Loréal, Olivier, Rannou-Bekono, Françoise and Derbré, Frédéric
Abstract

Physical inactivity increases the risk to develop type 2 diabetes, a disease characterized by a state of insulin resistance. By promoting inflammatory state, ceramides are especially recognized to alter insulin sensitivity in skeletal muscle. The present study was designed to analyze, in mice, whether muscle ceramides contribute to physical-inactivity-induced insulin resistance. For this purpose, we used the wheel lock model to induce a sudden reduction of physical activity, in combination with myriocin treatment, an inhibitor of de novo ceramide synthesis. Mice were assigned to 3 experimental groups: voluntary wheel access group (Active), a wheel lock group (Inactive), and wheel lock group treated with myriocin (Inactive-Myr). We observed that 10 days of physical inactivity induces hyperinsulinemia and increases basal insulin resistance (HOMA-IR). The muscle ceramide content was not modified by physical inactivity and myriocin. Thus, muscle ceramides do not play a role in physical-inactivity-induced insulin resistance. In skeletal muscle, insulin-stimulated protein kinase B phosphorylation and inflammatory pathway were not affected by physical inactivity, whereas a reduction of glucose transporter type 4 content was observed. Based on these results, physical-inactivity-induced insulin resistance seems related to a reduction in glucose transporter type 4 content rather than defects in insulin signaling. We observed in inactive mice that myriocin treatment improves glucose tolerance, insulin-stimulated protein kinase B, adenosine-monophosphate-activated protein kinase activation, and glucose transporter type 4 content in skeletal muscle. Such effects occur regardless of changes in muscle ceramide content. These findings open promising research perspectives to identify new mechanisms of action for myriocin on insulin sensitivity and glucose metabolism.

KeywordsNF-κB; HOMA-IR; AMP kinase; Akt; triglycerides
Year2019
JournalApplied Physiology, Nutrition and Metabolism
Journal citation44 (11), pp. 1180 - 1188
PublisherCanadian Science Publishing
ISSN1715-5320
Digital Object Identifier (DOI)https://doi.org/10.1139/apnm-2018-0850
Scopus EID2-s2.0-85074309042
Page range1180 - 1188
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationCanada
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