Identification and characterization of murine SCD4, a novel heart-specific stearoyl-CoA desaturase isoform regulated by leptin and dietary factors.
Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids. Thus far, three isoforms of SCD (SCD1, SCD2, and SCD3) have been identified and characterized. Regulation of the SCD1 isoform has been shown to be an important component of the metabolic actions of leptin in liver, but the effects of leptin on SCD isoforms in other tissues have not been investigated. We found that although the mRNA levels of SCD1 and SCD2 were not affected by leptin deficiency in the hearts of ob/ob mice, the SCD activity and levels of monounsaturated fatty acids were increased, implying the existence of another SCD isoform. This observation has led to the cDNA cloning and characterization of a fourth SCD isoform (SCD4) that is expressed exclusively in the heart. SCD4 encodes a 352-amino acid protein that shares 79% sequence identity with the SCD1, SCD2, and SCD3 isoforms. Liver X receptor alpha (LXR alpha) agonists and a high carbohydrate fat-free diet induced SCD4 expression, but unlike SCD1, SCD4 expression was not repressed by dietary polyunsaturated fatty acids. SCD4 mRNA levels were elevated 5-fold in the hearts of leptin-deficient ob/ob mice relative to wild type controls. Treatment of ob/ob mice with leptin decreased mRNA levels of SCD4, whereas levels of SCD1 and SCD2 were not affected. Furthermore, in the hearts of SCD1-deficient mice, SCD4 mRNA levels were induced 3-fold, whereas the levels of SCD2 were not altered. The current studies identify a novel heart-specific SCD isoform that demonstrates tissue-specific regulation by leptin and dietary factors.
Miyazaki
Makoto
M
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Jacobson
Mark J
MJ
Man
Weng Chi
WC
Cohen
Paul
P
Asilmaz
Esra
E
Friedman
Jeffrey M
JM
Ntambi
James M
JM
D000595:Amino Acid Sequence; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D015152:Blotting, Northern; D050260:Carbohydrate Metabolism; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004032:Diet; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D051379:Mice; D008820:Mice, Obese; D008861:Microsomes / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology*; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D014018:Tissue Distribution
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D020738:Leptin; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C477739:Scd4 protein, mouse; D013230:Stearoyl-CoA Desaturase