AMPK (AMP-activated protein kinase) has been suggested to be a central player regulating FA (fatty acid) metabolism through its ability to regulate ACC (acetyl-CoA carboxylase) activity. Nevertheless, its involvement in insulin resistance- and TD2 (Type 2 diabetes)-associated dyslipidaemia remains enigmatic. In the present study, we employed the Psammomys obesus gerbil, a well-established model of insulin resistance and TD2, in order to appreciate the contribution of the AMPK/ACC pathway to the abnormal hepatic lipid synthesis and increased lipid accumulation in the liver. Our investigation provided evidence that the development of insulin resistance/diabetic state in P. obesus is accompanied by (i) body weight gain and hyperlipidaemia; (ii) elevations of hepatic ACC-Ser79 phosphorylation and ACC protein levels; (iii) a rise in the gene expression of cytosolic ACC1 concomitant with invariable mitochondrial ACC2; (iv) an increase in hepatic AMPKα-Thr172 phosphorylation and protein expression without any modification in the calculated ratio of phospho-AMPKα to total AMPKα; (v) a stimulation in ACC activity despite increased AMPKα phosphorylation and protein expression; and (vi) a trend of increase in mRNA levels of key lipogenic enzymes [SCD-1 (stearoyl-CoA desaturase-1), mGPAT (mitochondrial isoform of glycerol-3-phosphate acyltransferase) and FAS (FA synthase)] and transcription factors [SREBP-1 (sterol-regulatory-element-binding protein-1) and ChREBP (carbohydrate responsive element-binding protein)]. Altogether, our findings suggest that up-regulation of the AMPK pathway seems to be a natural response in order to reduce lipid metabolism abnormalities, thus supporting the role of AMPK as a promising target for the treatment of TD2-associated dyslipidaemia.
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Research Article|
June 15 2009
Increased hepatic lipogenesis in insulin resistance and Type 2 diabetes is associated with AMPK signalling pathway up-regulation in Psammomys obesus
Ali Ben Djoudi Ouadda;
Ali Ben Djoudi Ouadda
*Research Centre, CHU-Sainte-Justine, 3175 Côte Ste-Catherine Road, Montreal, QC, Canada, H3T 1C5
†Department of Biochemistry, Université de Montréal, 2900 boul. Édouard-Montpetit, Montreal, QC, Canada, H3T 1J4
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Emile Levy;
Emile Levy
*Research Centre, CHU-Sainte-Justine, 3175 Côte Ste-Catherine Road, Montreal, QC, Canada, H3T 1C5
‡Department of Nutrition, Université de Montréal, 2405 chemin de la Côte-Ste-Catherine, Montreal, QC, Canada, H3T 1A8
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Ehud Ziv;
Ehud Ziv
§Diabetes Unit, Division of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel
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Geneviève Lalonde;
Geneviève Lalonde
*Research Centre, CHU-Sainte-Justine, 3175 Côte Ste-Catherine Road, Montreal, QC, Canada, H3T 1C5
‡Department of Nutrition, Université de Montréal, 2405 chemin de la Côte-Ste-Catherine, Montreal, QC, Canada, H3T 1A8
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Alain T. Sané;
Alain T. Sané
*Research Centre, CHU-Sainte-Justine, 3175 Côte Ste-Catherine Road, Montreal, QC, Canada, H3T 1C5
‡Department of Nutrition, Université de Montréal, 2405 chemin de la Côte-Ste-Catherine, Montreal, QC, Canada, H3T 1A8
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Edgar Delvin;
Edgar Delvin
*Research Centre, CHU-Sainte-Justine, 3175 Côte Ste-Catherine Road, Montreal, QC, Canada, H3T 1C5
†Department of Biochemistry, Université de Montréal, 2900 boul. Édouard-Montpetit, Montreal, QC, Canada, H3T 1J4
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Mounib Elchebly
Mounib Elchebly
1
*Research Centre, CHU-Sainte-Justine, 3175 Côte Ste-Catherine Road, Montreal, QC, Canada, H3T 1C5
†Department of Biochemistry, Université de Montréal, 2900 boul. Édouard-Montpetit, Montreal, QC, Canada, H3T 1J4
1To whom correspondence should be addressed (email mounib.elchebly@umontreal.ca).
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Publisher: Portland Press Ltd
Received:
September 15 2008
Revision Received:
September 30 2008
Accepted:
October 08 2008
Accepted Manuscript online:
October 08 2008
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biosci Rep (2009) 29 (5): 283–292.
Article history
Received:
September 15 2008
Revision Received:
September 30 2008
Accepted:
October 08 2008
Accepted Manuscript online:
October 08 2008
Citation
Ali Ben Djoudi Ouadda, Emile Levy, Ehud Ziv, Geneviève Lalonde, Alain T. Sané, Edgar Delvin, Mounib Elchebly; Increased hepatic lipogenesis in insulin resistance and Type 2 diabetes is associated with AMPK signalling pathway up-regulation in Psammomys obesus. Biosci Rep 1 October 2009; 29 (5): 283–292. doi: https://doi.org/10.1042/BSR20080141
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