title: NEU3 sialidase as a marker of insulin sensitivity: Regulation by fatty acids.
abstract: The plasma membrane-associated enzyme NEU3 sialidase functions to cleave sialic acid residues from the ganglioside GM3 thereby promoting its degradation, and has been implicated in the modulation of insulin action. Herein, we report for the first time that impaired insulin sensitivity in skeletal muscle and liver of obese Zucker fatty rats and aged C57BL/6 mice coincides with reduced NEU3 protein abundance. In addition, high fat feeding was found to significantly reduce NEU3 protein in white adipose tissue of rats. Notably, we also demonstrate the ability of the fatty acids palmitate and oleate to repress and induce NEU3 protein in L6 myotubes, concomitant with their insulin desensitising and enhancing effects, respectively. Moreover, we show that the palmitate-driven loss in NEU3 protein is mediated, at least in part, by intracellular ceramide synthesis but does not involve the proteasomal pathway. Strikingly, we further reveal that protein kinase B (PKB/Akt) acts as a key positive modulator of NEU3 protein abundance. Together, our findings implicate NEU3 as a potential biomarker of insulin sensitivity, and provide novel mechanistic insight into the regulation of NEU3 expression.
authors.affiliation: Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lipina
authors.affiliation: Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nardi
authors.affiliation: Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Grace
authors.affiliation: Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address: h.s.hundal@dundee.ac.uk.
authors.forename: Harinder S
authors.initials: HS
authors.lastname: Hundal
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000201:enzymology* / Q000473:pathology; D009439:Neuraminidase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D051057:Proto-Oncogene Proteins c-akt; C511796:Neu3 protein, mouse; D009439:Neuraminidase
keywords: Ageing; Ganglioside GM3; Insulin resistance; NEU3 sialidase; Obesity; Protein kinase B