Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice.

Abstract

Obesity and adiposity greatly increase the risk for secondary conditions such as insulin resistance. Mice deficient in the enzyme stearoyl-CoA desaturase-1 (SCD1) are lean and protected from diet-induced obesity and insulin resistance. In order to determine the effect of SCD1 deficiency on various mouse models of obesity, we introduced a global deletion of the Scd1 gene into leptin-deficient ob/ob mice, leptin-resistant Agouti (A(y)/a) mice, and high-fat diet-fed obese (DIO) mice. SCD1 deficiency lowered body weight, adiposity, hepatic lipid accumulation, and hepatic lipogenic gene expression in all three mouse models. However, glucose tolerance, insulin, and leptin sensitivity were improved by SCD1 deficiency only in A(y)/a and DIO mice, but not ob/ob mice. These data uncouple the effects of SCD1 deficiency on weight loss from those on insulin sensitivity and suggest a beneficial effect of SCD1 inhibition on insulin sensitivity in obese mice that express a functional leptin gene.

• Authors: Makoto Miyazaki, Harini Sampath, Xueqing Liu, Matthew T Flowers, Kiki Chu, Agnieszka Dobrzyn, James M Ntambi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 380 Issue 4 Pg. 818-22 (Mar 20 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19338759 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Agouti Signaling Protein
• Insulin
• Leptin
• a protein, mouse
• Scd1 protein, mouse
• Stearoyl-CoA Desaturase

Topics

• Adiposity (genetics)
• Agouti Signaling Protein (genetics)
• Animals
• Glucose Tolerance Test
• Insulin (pharmacology)
• Insulin Resistance (genetics)
• Leptin (metabolism, pharmacology)
• Mice
• Mice, Mutant Strains
• Obesity (enzymology, genetics)
• Stearoyl-CoA Desaturase (deficiency, genetics)