Overproduction of intestinal lipoprotein containing apolipoprotein B-48 in Psammomys obesus: impact of dietary n-3 fatty acids.
OBJECTIVE
Emerging evidence underscores the important role of the small intestine in the pathogenesis of dyslipidaemia in insulin resistance and type 2 diabetes. We therefore tested the hypothesis that n-3 fatty acids improve the various events governing intra-enterocyte lipid transport in Psammomys obesus gerbils, a model of nutritionally induced metabolic syndrome.


METHODS
Experiments were carried out on Psammomys obesus gerbils that were assigned to an isocaloric control diet and a diet rich in fish oil for 6 weeks.


RESULTS
Increased dietary intake of fish oil lowered body weight and improved hyperglycaemia and hyperinsulinaemia. It simultaneously decreased de novo intestinal lipogenesis and lipid esterification of the major lipid classes, e.g. triglycerides, phospholipids and cholesteryl esters, particularly in insulin-resistant and diabetic animals. Accordingly, lessened activity of monoacylglycerol and diacylglycerol acyltransferase was recorded. As assessed in cultured jejunal explants incubated with either [(14)C]-oleic acid or [(35)S]-methionine, fish oil feeding resulted in diminished triglyceride-rich lipoprotein assembly and apolipoprotein (apo) B-48 biogenesis, respectively. The mechanisms did not involve apo B-48 transcription or alter the gene expression and activity of the critical microsomal triglyceride transfer protein. Rather, the suppressed production of apo B-48 by n-3 fatty acids was associated with intracellular proteasome-mediated posttranslational downregulation in insulin-resistant and diabetic animals.


CONCLUSIONS
Our data highlight the beneficial impact of n-3 fatty acids on adverse effects of the metabolic syndrome and emphasise their influence on intestinal lipid transport, an effect which may limit postprandial lipaemia and the risk of atherosclerosis.
Levy
E
E
Department of Nutrition, Research Centre, Sainte-Justine Hospital and University of Montréal, 3175 Côte Ste-Catherine Road, Montreal, Quebec, H3T 1C5, Canada. emile.levy@recherche-ste-justine.qc.ca
Spahis
S
S
Ziv
E
E
Marette
A
A
Elchebly
M
M
Lambert
M
M
Delvin
E
E
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005849:Gerbillinae; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D009924:Organ Culture Techniques
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D008074:Lipoproteins; D000217:Acyltransferases