N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle.
A high-fat diet containing polyunsaturated fatty acids (PUFA: n-3 or n-6) given for 4 wk to 5-wk-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 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 IR substrate (IRS)-1 tyrosine phosphorylation, and phosphatidylinositol (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; 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 at normal levels in rats fed with n-3 PUFA compared with rats fed a normal diet. In rats 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 reductions in p85 expression, respectively, whereas GLUT-4 and leptin expression was depressed in n-6 rats. The expression was not affected in n-3 rats compared with control rats. In conclusion, a high-fat diet enriched in n-3 fatty acids maintained IR, IRS-1 tyrosine phosphorylation, and PI 3'-kinase activity and total GLUT-44 content in muscle but not in liver. A high-fat diet (n-3) partially altered the expression of p85 but not that of GLUT-4 and leptin mRNAs in adipose tissue.
Taouis
Mohammed
M
Station de Recherches Avicoles, Institut National de la Recherche Agronomique Centre de Tours, 37380 Nouzilly, France. taouis@tours.inra.fr
Dagou
Carine
C
Ster
Céline
C
Durand
Georges
G
Pinault
Michèle
M
Delarue
Jacques
J
D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D001786:Blood Glucose; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D020738:Leptin; D008055:Lipids; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin