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Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation

Stephens, Francis B.; Mendis, Buddhike; Shannon, Chris E.; Cooper, Scott; Ortori, Catharine A.; Barrett, David A.; Mansell, Peter; Tsintzas, Kostas

Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation Thumbnail


Authors

Buddhike Mendis

Chris E. Shannon

Scott Cooper

Catharine A. Ortori

David A. Barrett

Peter Mansell

KOSTAS TSINTZAS kostas.tsintzas@nottingham.ac.uk
Professor of Human Physiology



Abstract

Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic–hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload.

Journal Article Type Article
Acceptance Date Mar 10, 2014
Online Publication Date Sep 1, 2014
Publication Date Sep 1, 2014
Deposit Date Aug 17, 2017
Publicly Available Date Aug 17, 2017
Journal Clinical Science
Print ISSN 0143-5221
Electronic ISSN 1470-8736
Publisher Portland Press
Peer Reviewed Peer Reviewed
Volume 127
Issue 5
Pages 315-322
DOI https://doi.org/10.1042/cs20140031
Keywords acylcarnitine, insulin sensitivity, mitochondrial overload, omega-3 polyunsaturated fatty acid, pyruvate dehydrogenase, skeletal muscle
Public URL https://nottingham-repository.worktribe.com/output/733427
Publisher URL http://www.clinsci.org/content/127/5/315