title: Docosahexaenoic acid impairs the maturation of very low density lipoproteins in rat hepatic cells.
abstract: One mechanism of the lipid-lowering effects of the fish oil n-3 fatty acids [e.g., docosahexaenoic acid (DHA)] in cell and animal models is induced hepatic apolipoprotein B100 (apoB) presecretory degradation. This degradation occurs post-endoplasmic reticulum, but whether DHA induces it before or after intracellular VLDL formation remains unanswered. We found in McA-RH7777 rat hepatic cells that DHA and oleic acid (OA) treatments allowed formation of pre-VLDL particles and their transport to the Golgi, but, in contrast to OA, with DHA pre-VLDL particles failed to quantitatively assemble into fully lipidated (mature) VLDL. This failure required lipid peroxidation and was accompanied by the formation of apoB aggregates (known to be degraded by autophagy). Preventing the exit of proteins from the Golgi blocked the aggregation of apoB but did not restore VLDL maturation, indicating that failure to fully lipidate apoB preceded its aggregation. ApoB autophagic degradation did not appear to require an intermediate step of cytosolic aggresome formation. Taken with other examples in the literature, the results of this study suggest that pre-VLDL particles that are competent to escape endoplasmic reticulum quality control mechanisms but fail to mature in the Golgi remain subject to quality control surveillance late in the secretory pathway.
authors.affiliation: Departments of Medicine (Leon H. Charney Division of Cardiology) and Cell Biology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY 10016; and.
authors.forename: Vatsala
authors.initials: V
authors.lastname: Maitin
authors.forename: Ursula
authors.initials: U
authors.lastname: Andreo
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001055:Apolipoproteins B; D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D015227:Lipid Peroxidation; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D051381:Rats
chemical_list: D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D004281:Docosahexaenoic Acids
keywords: Golgi; apoB; autophagy; endoplasmic reticulum; lipid peroxidation