Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart

Pawel Dobrzyn, Harini Sampath, Agnieszka Dobrzyn, Makoto Miyazaki, James M Ntambi
American Journal of Physiology. Endocrinology and Metabolism 2008, 294 (2): E357-64
Stearoyl-CoA desaturase (SCD) is a lipogenic enzyme that catalyzes the synthesis of monounsaturated fatty acids (FA). SCD1 deficiency activates metabolic pathways that promote FA beta-oxidation and decrease lipogenesis in liver. In the present study, we show that FA transport and oxidation are decreased, whereas glucose uptake and oxidation are increased in the heart of SCD1(-/-) mice. Protein levels of FA transport proteins such as FA translocase/CD36 and FA transport protein as well as activity of carnitine palmitoyltransferase 1, the rate-limiting enzyme for mitochondrial fat oxidation, were significantly lower in the heart of SCD1(-/-) mice compared with SCD1(+/+) mice. Consequently, the rate of palmitoyl-CoA oxidation was decreased significantly in the heart of SCD1(-/-) mice. mRNA levels of peroxisome proliferator-activated receptor-alpha, a key transcription factor controlling genes of FA oxidation, were significantly reduced in SCD1(-/-) mice. Phosphorylation of insulin receptor substrate-1 (IRS-1) and the association of alphap85 subunit of phosphatidylinositol 3-kinase with IRS-1 were significantly higher under both basal and insulin-stimulated conditions in SCD1(-/-) hearts. This increased insulin sensitivity translated to a 1.8-fold greater 2-deoxyglucose uptake and 2-fold higher rate of glucose oxidation in the myocardium compared with SCD1(+/+) counterparts. The results suggest that SCD1 deficiency causes a shift in cardiac substrate utilization from FA to glucose by upregulating insulin signaling, decreasing FA availability, and reducing expression of FA oxidation genes in the heart. This increase in cardiac insulin sensitivity and glucose utilization due to SCD1 deficiency could prove therapeutic in pathological conditions such as obesity that are characterized by skewed cardiac substrate utilization.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"