title: Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance.
abstract: Insulin resistance (IR) is associated with elevated plasma levels of triglyceride-rich lipoproteins (TRLs) of intestinal origin. However, the mechanisms underlying the overaccumulation of apolipoprotein (apo)B-48-containing TRLs in individuals with IR are not yet fully understood. This study examined the relationships between apoB-48-containing TRL kinetics and the expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism in 14 obese nondiabetic men with IR compared with 10 insulin-sensitive (IS) men matched for waist circumference. The in vivo kinetics of TRL apoB-48 were assessed using a primed-constant infusion of L-[5,5,5-D₃]leucine for 12 h with the participants in a constantly fed state. The expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism was assessed by performing real-time PCR quantification and LC-MS/MS on duodenal biopsy specimens. The TRL apoB-48 pool size and production rate were 102% (P < 0.0001) and 87% (P = 0.01) greater, respectively, in the men with IR versus the IS men. On the other hand, intestinal mRNA levels of sterol regulatory element binding factor-2, hepatocyte nuclear factor-4α, and microsomal triglyceride transfer protein were significantly lower in the men with IR than in the IS men. These data indicate that IR is associated with intestinal overproduction of lipoproteins and significant downregulation of key intestinal genes involved in lipid/lipoprotein metabolism.
authors.affiliation: Institute of Nutrition and Functional Foods Centre Hospitalier de l'Université Laval (CHUL) Research Centre.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
authors.forename: André J
authors.initials: AJ
authors.lastname: Tremblay
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kelly
authors.forename: Valéry
authors.initials: V
authors.lastname: Lemelin
authors.forename: Arnaud
authors.initials: A
authors.lastname: Droit
authors.forename: Benoît
authors.initials: B
authors.lastname: Lamarche
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D053283:Apolipoprotein B-48 / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose; D016022:Case-Control Studies; D015536:Down-Regulation; D004386:Duodenum / Q000378:metabolism*; D050171:Dyslipidemias / Q000235:genetics* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D007700:Kinetics; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
chemical_list: D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides
keywords: apolipoprotein B-100; apolipoprotein B-48; cholesterol; fatty acids; intestine; kinetic