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

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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 β-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-α, 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 αp85 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume294
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

Stearoyl-CoA Desaturase
Fatty Acids
Glucose
Oxidation
Fatty Acid Transport Proteins
Insulin Receptor Substrate Proteins
Insulin
Insulin Resistance
Phosphatidylinositol 3-Kinase
Palmitoyl Coenzyme A
Genes
Carnitine O-Palmitoyltransferase
Monounsaturated Fatty Acids
Lipogenesis
Peroxisome Proliferator-Activated Receptors
Deoxyglucose
Phosphorylation
Enzymes
Metabolic Networks and Pathways
Substrates

Keywords

  • Carnitine palmitoyltransferase 1
  • Fatty acid transport proteins
  • Insulin signaling
  • Peroxisome proliferator-activated receptor α

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart. / Dobrzyn, Pawel; Sampath, Harini; Dobrzyn, Agnieszka; Miyazaki, Makoto; Ntambi, James M.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 294, No. 2, 02.2008.

Research output: Contribution to journalArticle

Dobrzyn, Pawel ; Sampath, Harini ; Dobrzyn, Agnieszka ; Miyazaki, Makoto ; Ntambi, James M. / Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart. In: American Journal of Physiology - Endocrinology and Metabolism. 2008 ; Vol. 294, No. 2.
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abstract = "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 β-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-α, 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 αp85 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.",
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