title: Chylomicron remnants and nonesterified fatty acids differ in their ability to inhibit genes involved in lipogenesis in rats.
abstract: Primary hepatocytes treated with nonesterified PUFA have been used as a model for analyzing the inhibitory effects of dietary polyunsaturated fats on lipogenic gene expression. Although nonesterified fatty acids play an important signaling role in starvation, they do not completely recapitulate the mechanism of dietary fat presentation to the liver, which is delivered via chylomicron remnants. To test the effect of remnant TG on lipogenic enzyme expression, chylomicron remnants were generated from the lymph of rats intubated with either safflower oil or lard. The remnants were added to the medium of primary rat hepatocytes in culture and the accumulation of mRNA for genes involved in carbohydrate and lipid metabolism was measured. Both PUFA-enriched remnants and nonesterified PUFA inhibited the expression and maturation of sterol response element binding protein-1c (SREBP-1c) and the expression of lipogenic genes regulated by this transcription factor. These remnants also inhibited the expression of glucose-6-phosphate dehydrogenase (G6PD), a gene regulated at post-transcriptional steps. In contrast, PUFA-enriched remnants did not inhibit the accumulation of mRNA for malic enzyme, glucokinase, and L-pyruvate kinase, whereas nonesterified fatty acids caused a decrease in these mRNA. These genes are regulated independently of SREBP-1c. SFA-enriched remnants did not inhibit lipogenic gene expression, which is consistent with a lack of inhibition of lipogenesis by dietary saturated fats. Thus, the inhibitory action of dietary polyunsaturated fats on lipogenesis involves a direct action of chylomicron remnants on the liver.
authors.affiliation: Department of Biochemistry, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Alison B
authors.initials: AB
authors.lastname: Kohan
authors.forename: Yang
authors.initials: Y
authors.lastname: Qing
authors.forename: Holly A
authors.initials: HA
authors.lastname: Cyphert
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Salati
mesh_terms: D000818:Animals; D053298:Chylomicron Remnants / Q000378:metabolism / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D053298:Chylomicron Remnants; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D005954:Glucosephosphate Dehydrogenase