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J. Biol. Chem., Vol. 279, Issue 18, 19362-19374, April 30, 2004

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Regulation of Hepatic Apolipoprotein B-lipoprotein Assembly and Secretion by the Availability of Fatty Acids

I. DIFFERENTIAL RESPONSE TO THE DELIVERY OF FATTY ACIDS VIA ALBUMIN OR REMNANT-LIKE EMULSION PARTICLES^*

Yuan-Li Zhang, Antonio Hernandez-Ono, Carol Ko, Koichi Yasunaga, Li-Shin Huang, and Henry N. Ginsberg¶

From the Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032

The in vivo effects of increased delivery of fatty acids (FA) to the liver are poorly defined. Therefore, we compared the effects of infusing either 6 mM oleic acid (OA) bound to albumin, 0.5-20% Intralipid, or saline for 3 or 6 h into male C57BL/6J mice. Infusions were followed by studies of triglyceride (TG) and apoB secretion. Although plasma FA levels increased similarly after either 20% Intralipid or 6 mM OA, TG secretion increased only after infusion of 4-20% Intralipid; TG secretion was unchanged by 6 mM OA. By contrast, 6-h infusions of either 6 mM OA or 4-20% Intralipid increased apoB secretion. 6 mM OA and 20% Intralipid each increased secretion of apoB from primary hepatocytes ex vivo. Importantly, 0.5-2% Intralipid, which delivered more FA to the liver than 6 mM OA, did not stimulate apoB secretion. Hepatic apoB mRNA levels were unaffected by either 6 mM OA or 20% Intralipid, but microsomal triglyceride transfer protein mRNA was significantly lower after 6-h infusions with 6 mM OA versus either saline or 20% Intralipid. Lower microsomal triglyceride transfer protein mRNA levels were associated with reduced hepatic TG mass after 6-h infusions of 6 mM OA. We conclude that 1) increased FA delivery to the liver in vivo increases secretion of apoB-lipoproteins via post-transcriptional mechanisms, 2) OA-induced apoB-lipoprotein secretion occurred at least in part via mechanisms other than by providing substrate for TG synthesis, and 3) the route of delivery of FA is important for its effects on apoB secretion.

Received for publication, January 9, 2004

^* This work was supported by NHLBI, National Institutes of Health Grants HL 55368 (to H. N. G.) and HL 62583 (to L.-S. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Visiting scholar from the Chinese Academy of Medical Sciences at Peking Union Medical College Hospital.

^¶ To whom correspondence should be addressed: Dept. of Medicine, PH 10-305, Columbia University College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032; E-mail: hng1{at}columbia.edu.

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