title: Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia.
abstract: Stearoyl-CoA desaturase (SCD) is expressed at high levels in several human tissues and is required for the biosynthesis of oleate (18:1) and palmitoleate (16:1). These monounsaturated fatty acids are the major components of phospholipids, triglycerides, wax esters, and cholesterol esters. Mice with a targeted disruption of the SCD1 gene have very low levels of VLDL and impaired triglyceride and cholesterol ester biosynthesis. In the HYPLIP mouse, a model of hyperlipidemia, there was a 4-fold increase in hepatic SCD activity, a 1.8-fold increase in the desaturation index, and a 2-fold increase in plasma triglycerides. We used the plasma ratio of 18:1/18:0 (the "desaturation index") as an in vivo measure of SCD activity in human subjects. In human subjects with triglycerides ranging from 0.3 to 20 mM, the desaturation ratio accounted for one-third of the variance in plasma triglyceride levels. A 2-fold increase in the desaturation index was associated with a 4-fold increase in plasma triglycerides. In human subjects exposed to a high carbohydrate diet, the desaturation index explained 44% of the variance in triglycerides. We propose that many of the factors that influence plasma triglyceride levels do so by converging upon the regulation of SCD activity.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. attie@biochem.wisc.edu
authors.forename: Alan D
authors.initials: AD
authors.lastname: Attie
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.forename: Mark P
authors.initials: MP
authors.lastname: Gray-Keller
authors.forename: Alison
authors.initials: A
authors.lastname: Brownlie
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyazaki
authors.forename: John J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Stoehr
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
mesh_terms: D000818:Animals; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004195:Disease Models, Animal; D018628:Gene Dosage; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000201:enzymology*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D018709:Statistics, Nonparametric; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood*; D044465:White People
chemical_list: D004040:Dietary Carbohydrates; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D013230:Stearoyl-CoA Desaturase