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.
| Original language | English |
|---|---|
| Pages (from-to) | 1742-1750 |
| Number of pages | 9 |
| Journal | Cellular Signalling |
| Volume | 27 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1 Sep 2015 |
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Keywords
- Ageing
- Ganglioside GM3
- Insulin resistance
- NEU3 sialidase
- Obesity
- Protein kinase B
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NEU3 sialidase as a marker of insulin sensitivity : Regulation by fatty acids. / Lipina, Christopher; Nardi, Francesca; Grace, Helen; Hundal, Harinder S. (Lead / Corresponding author).
In: Cellular Signalling, Vol. 27, No. 9, 01.09.2015, p. 1742-1750.Research output: Contribution to journal › Article
TY - JOUR
T1 - NEU3 sialidase as a marker of insulin sensitivity
T2 - Regulation by fatty acids
AU - Lipina, Christopher
AU - Nardi, Francesca
AU - Grace, Helen
AU - Hundal, Harinder S.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Ageing
KW - Ganglioside GM3
KW - Insulin resistance
KW - NEU3 sialidase
KW - Obesity
KW - Protein kinase B
UR - http://www.scopus.com/inward/record.url?scp=84930645422&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2015.05.010
DO - 10.1016/j.cellsig.2015.05.010
M3 - Article
C2 - 26022181
AN - SCOPUS:84930645422
VL - 27
SP - 1742
EP - 1750
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 9
ER -