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Articles in PresS, published online ahead of print October 29, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00320.2001
Submitted on July 17, 2001
Accepted on October 25, 2001
1 Station de Recherches Avicoles, INRA, Nouzilly, France
2 Nutrition, INRA, Jouy en Josas, France
3 Nutrition, University of Tours, Tours, France
4 Nutrition, University of Brest, Brest, France
* To whom correspondence should be addressed. E-mail: taouis{at}tours.inra.fr.
High fat diet containing polyunsaturated fatty acids (PUFA : n-3 or n-6) given for four weeks to 5 week-old male wistar rats induced a clear hyperglycemia (10.4 ± 0.001 mmol/L for n-6 rats and 10.1 ± 0.001 for n-3 rats) and hyperinsulinemia (6.6 ± 0.8 ng/mL for n-6 rats and 6.4 ± 1.3 ng/mL for n-3 rats) signs of insulin-resistance. In liver, both diets (n-3) and (n-6) significantly reduced insulin receptor (IR) number, IR and IRS-1 tyrosine phosphorylation as well as the PI 3' kinase activity. In contrast, in leg muscle, IR density, as determined by western-blotting, was not affected whereas IR and IRS-1 tyrosine phosphorylation in response to insulin treatment was restored in animals fed with (n-3) PUFA to normal whereas in (n-6) PUFA the phosphorylation was depressed as evidenced by western-blot analysis using specific antibodies. In addition, PI 3' kinase activity and Glut 4 content in muscle were maintained to normal in rat fed with (n-3) PUFA as compared to rat fed with normal diet whereas in rat fed with (n-6) PUFA both PI 3' kinase activity and Glut 4 content were reduced. Furthermore, in adipose tissue and using RT-PCR we show that both (n-3) and (n-6) PUFA led to slight or strong reduction in p85 expression, respectively ; whereas Glut4 and leptin expression was depressed in (n-6) rats but the expression was not affected in (n-3) rats compared to control rats. In conclusion, high fat diet enriched in (n-3) fatty acids maintained IR, IRS-1 tyrosine phosphorylation and PI 3 kinase activity and total Glut 4 content in muscle but not in liver. High fat diet (n-3) partially altered the expression of p85 but not that of Glut 4 and leptin mRNAs in adipose tissue
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