Changes in Hepatic ApoAV Expression are not Required for the Rapid Triglyceride Lowering Effect of Fish Oil Diet in Rats

Introduction

Diets rich in polyunsaturated ω-3 or ω-6 fatty acids (PUFA) reduce fasting and postprandial plasma triglyceride levels by a rapid suppression of hepatic VLDL secretion and possibly by accelerated chylomicron clearance. ApoAV is a newly identified apolipoprotein of hepatic origin circulating bound to triglyceride rich lipoproteins and HDL at very low plasma levels [1] [2]. Human APOA5 polymorphisms are associated with elevated plasma triglycerides [1]. ApoAV deficiency leads to severe hypertriglyceridemia [3]. In genetically modified mice apoAV has a marked triglyceride-lowering effect due to stimulation of proteoglycan-bound lipoprotein lipase and possibly due to reduction of hepatic VLDL production [1] [4] [5] [6]. Thus, an increase of Apoa5 expression conceivably could play a role in the rapid triglyceride-lowering effect of diets rich in PUFA.

The present study was designed to determine whether Apoa5 gene expression is altered during the initial phase of a fish oil diet using rats adapted to a single meal per day. Apoa4, the apolipoprotein most homologous to apoAV, and Spot 14 (S14) a nuclear protein involved in lipogenesis were studied as controls. Both are suppressed transcriptionally by PUFA feeding [7] [8].

References

• 1 Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, Krauss RM, Rubin EM. Science. 2001;  294 169-173
• 2 Vliet HN van der, Sammels MG, Leegwater AC, Levels JH, Reitsma PH, Boers W, Chamuleau RA. J Biol Chem. 2001;  276 44512-44520
• 3 Oliva CP, Pisciotta L, Li Volti G, Sambataro MP, Cantafora A, Bellocchio A, Catapano A, Tarugi P, Bertolini S, Calandra S. Arterioscler Thromb Vasc Biol. 2005;  25 411-417
• 4 Fruchart-Najib J, Bauge E. Biochem Biophys Res Commun. 2004;  319 397-404
• 5 Schaap FG, Rensen PC, Voshol PJ, Vrins C, Vliet HN van der, Chamuleau RA, Havekes LM, Groen AK, van Dijk KW. J Biol Chem. 2004;  279 27941-27947
• 6 Merkel M, Loeffler B, Kluger M, Fabig N, Geppert G, Pennacchio L, Laatsch A, Heeren J. J Biol Chem. 2005;  280 21553-21560
• 7 Jump DB, Clarke SD, MacDougald O, Thelen A. Proc Natl Acad Sci USA. 1993;  90 8454-8458
• 8 Strobl W, Knerer B, Gratzl R, Arbeiter K, Lin-Lee YC, Patsch W. J Clin Invest. 1993;  92 1766-1773
• 9 Dorfmeister B, Brandlhofer S, Schaap FG, Hermann M, Fürnsinn C, Hagerty BP, Stangl H, Patsch W, Strobl W. Diabetologia. 2006;  49 1324-1332
• 10 Weintraub MS, Zechner R, Brown A, Eisenberg S, Breslow JL. J Clin Invest. 1988;  82 1884-1893
• 11 Grosskopf I, Baroukh N, Lee SJ, Kamari Y, Harats D, Rubin EM, Pennacchio LA, Cooper AD. Arterioscler Thromb Vasc Biol. 2005;  25 2573-2579
• 12 Weinberg RB, Cook VR, Beckstead JA, Martin DD, Gallagher JW, Shelness GS, Ryan RO. J Biol Chem. 2003;  278 34438-34444
• 13 Schuller E, Patel N, Item C, Greber-Platzer S, Baran H, Patsch W, Strobl W. Int J Obes Relat Metab Disord. 2000;  24 460-467

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