Stearoyl-CoA desaturase - a new player in skeletal muscle metabolism regulation

• Autorzy: Dobrzyn A. , Dobrzyn P.
• Języki publikacji: EN

Abstrakty

EN

Stearoyl-CoA desaturase (SCD) is a rate-limiting enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate (16:1), which are a major component of tissue lipids. SCD1 deficient mice reveal increased energy expenditure and decreased body adiposity due to the upregulation of genes of fatty acid oxidation and the downregulation of genes of lipid synthesis in liver. In this review, we examine data showing that SCD is an important component in the regulation of skeletal muscle metabolism, which affects insulin sensitivity, mitochondrial fatty acid oxidation and ceramide de novo synthesis in oxidative myofibers. The lack of SCD1 gene increases the rate of fatty acid ß-oxidation through activation of the AMP-activated protein kinase (AMPK) pathway and by upregulating genes of fatty acid oxidation in soleus and red gastrocnemius muscles. Consistent with increased ß-oxidation, the contents of free fatty acids and long-chain acyl-CoAs are significantly decreased, which together with reduced mRNA level and activity of serine palmitoyltransferase led to reduced ceramide synthesis in oxidative muscles of SCD1-/- mice. Thus, reduced contents of free fatty acids, acyl-CoAs and ceramides as well as increased AMPK phosphorylation, might contribute to increased insulin sensitivity observed in muscle of SCD1-/- mice. SCD1 deficiency also results in downregulation of the expression of the protein-tyrosine phosphatase 1B, which is responsible for the sustained insulin receptor autophosphorylation despite reduced levels of plasma insulin in the SCD1-/- mice. SCD1 deficiency reduced ceramide synthesis, increased AMPK phosphorylation and carnitine palmitoyltransferase 1 activity also in soleus and red gastrocnemius muscles of leptin deficient ob/ob mice. These findings raise the possibility that SCD1 may be a downstream component of the leptin signaling pathway in skeletal muscle.

Słowa kluczowe

EN

steaoryl-CoA desaturase; skeletal muscle; metabolism regulation; monounsaturated fatty acid; tissue lipid; fatty acid oxidation; lipid synthesis; liver; SCD 1 gene; protein kinase; gastrocnemius muscle; insulin; ceramide; oxidative muscle

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology. Supplement
• Rocznik: 2006
• Tom: 57
• Numer: 10
• Strony: 31-42
• Opis fizyczny: p.31-42,fig.,ref.

Twórcy

autor

Dobrzyn A.

• Medical University of Bialystok, 2C Mickiewicza Str., 15-089 Bialystok, Poland

autor

Dobrzyn P.