Combined effects of EFA deficiency and tumor necrosis factor-alpha on circulating lipoproteins in rats.
Both tumor necrosis factor-alpha (TNF-alpha) and EFA deficiency (EFAD) have been established as causes of marked perturbations in lipid and lipoprotein metabolism. Excessive levels of circulating TNF-alpha can coexist with EFAD in various clinical disorders such as cystic fibrosis and type I diabetes. The present study therefore aimed to investigate their combined effects on lipid profile and lipoprotein composition by administering TNF-alpha to EFAD rats. Lipoprotein lipase (LPL), the rate-limiting enzyme in TG catabolism, was also measured in epididymal adipose tissue. EFAD, after a 4-wk period, induced significant increases in plasma TG (80%, P < 0.001), total cholesterol (TC, 27%, P < 0.025), and HDL-cholesterol (HDL-C, 62%). Two hours after the administration of TNF-alpha, a further rise in TG (43%, P < 0.05) was noted in controls, but not EFAD animals. TC and HDL-C were unaffected by TNF-alpha treatment. In addition, TNF-alpha modified lipoprotein-lipid composition. VLDL and HDL2 derived from EFAD rats were depleted in apolipoprotein (apo) E and apo A-II, and enriched in apo A-I 2 h after TNF-alpha administration. Finally, TNF-alpha decreased adipose tissue LPL activity in both control and EFAD animals. The TNF-alpha-induced inhibition was more marked in EFAD rats. The present results demonstrated that TNF-alpha can amplify or antagonize the effects of EFAD on lipid profile, lipoprotein composition, and LPL activity. These data also suggest that the host's nutritional status is a determining factor for the modulating effect of TNF-alpha on lipid metabolism.
Levy
Emile
E
Department of Nutrition, Centre de Recherche, Hôpital Ste-Justine, Université de Montréal, Montréal, Québec, Canada, H3T 1C5. levye@justine.umontreal.ca
Delvin
Edgard
E
Peretti
Noel
N
Bouchard
Guylaine
G
Seidman
Ernest
E
D000818:Animals; D005228:Fatty Acids, Essential / Q000097:blood* / Q000172:deficiency*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D005228:Fatty Acids, Essential; D008074:Lipoproteins; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase