n-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity?

Type Article
Date 2004-05
Language English
Author(s) Delarue Jacques1, 2, Lefoll Christelle1, Corporeau Charlotte1, Lucas Daniele1
Affiliation(s) 1 : Fac Med, EA Oxylipides 948, F-29200 Brest, France.
2 : CHU Cavale Blanche, Lab Reg Nutr Humaine, F-29200 Brest, France.
Meeting 2nd Symposium on Anomalies of Fatty Acids, Ageing and Degenerating Pathologies for the French-Speaking Community, Paris, FRANCE, JAN, 2002
Source Reproduction Nutrition Development (0926-5287) (Edp Sciences S A), 2004-05 , Vol. 44 , N. 3 , P. 289-299
DOI 10.1051/rnd:2004033
WOS© Times Cited 157
Keyword(s) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), peroxisome proliferator-activated receptors (PPAR), non alcoholic steatohepatitis, glucose metabolism, insulin resistance
Abstract

n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), mainly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), are present in mammal tissues both from endogenous synthesis from desaturation and elongation of 18:3 n-3 and/or from dietary origin (marine products and fish oils). In rodents in vivo, n-3 LC-PUFA have a protective effect against high fat diet induced insulin resistance. Such an effect is explained at the molecular level by the prevention of many alterations of insulin signaling induced by a high fat diet. Indeed, the protective effect of n-3 LC-PUFA results from the following: (a) the prevention of the decrease of phosphatidyl inositol 3' kinase (PI3 kinase) activity and of the depletion of the glucose transporter protein GLUT4 in the muscle; (b) the prevention of the decreased expression of GLUT4 in adipose tissue. In addition, n-3 LC-PUFA inhibit both the activity and expression of liver glucose-6-phosphatase which could explain the protective effect with respect to the excessive hepatic glucose output induced by a high fat diet. n-3 LC-PUFA also decrease muscle intramyofibrillar triglycerides and liver steatosis. This last effect results on the one hand, from a decreased expression of lipogenesis enzymes and of delta 9 desaturase (via a depleting effect on sterol response element binding protein 1c (SREBP-1c). On the other hand, n-3 LC-PUFA stimulate fatty acid oxidation in the liver (via the activation of peroxisome proliferator activated receptor alpha (PPAR-alpha)). In patients with type 2 diabetes, fish oil dietary supplementation fails to reverse insulin resistance for unclear reasons, but systematically decreases plasma triglycerides. Conversely, in healthy humans, fish oil has many physiological effects. Indeed, fish oil reduces insulin response to oral glucose without altering the glycaemic response, abolishes extraggression at times of mental stress, decreases the activation of sympathetic activity during mental stress and also decreases plasma triglycerides. These effects are encouraging in the perspective of prevention of insulin resistance but further clinical and basic studies must be designed to confirm and complete our knowledge in this field.

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Delarue Jacques, Lefoll Christelle, Corporeau Charlotte, Lucas Daniele (2004). n-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? Reproduction Nutrition Development, 44(3), 289-299. Publisher's official version : https://doi.org/10.1051/rnd:2004033 , Open Access version : https://archimer.ifremer.fr/doc/00654/76580/