Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.
Stearoyl-CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Several SCD isoforms (SCD1-3) exist in the mouse. Here we show that mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced weight gain. The protection from obesity involves increased energy expenditure and increased oxygen consumption. Compared with the wild-type mice the SCD1-/- mice have increased levels of plasma ketone bodies but reduced levels of plasma insulin and leptin. In the SCD1-/- mice, the expression of several genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down-regulated. These observations suggest that a consequence of SCD1 deficiency is an activation of lipid oxidation in addition to reduced triglyceride synthesis and storage.
Ntambi
James M
JM
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. ntambi@biochem.wisc.edu
Miyazaki
Makoto
M
Stoehr
Jonathan P
JP
Lan
Hong
H
Kendziorski
Christina M
CM
Yandell
Brian S
BS
Song
Yang
Y
Cohen
Paul
P
Friedman
Jeffrey M
JM
Attie
Alan D
AD
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004041:Dietary Fats; D005260:Female; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009765:Obesity / Q000517:prevention & control*; D010101:Oxygen Consumption; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D004041:Dietary Fats; D013230:Stearoyl-CoA Desaturase