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Stearoyl-coenzym a desaturase as a terapeutic target of metabolic disease

Publication at First Faculty of Medicine |
2017

Abstract

Stearoyl- CoA desaturase is a key enzyme in lipogenesis. This fact is crucial for its physiological and pathophysiological properties.

Stearoyl-CoA desaturase is an enzyme responsible in desaturation process of saturated fatty acids changing them to monounsaturated fatty acids. Stearoyl-CoA desaturase has some isoforms, isoform called SCD-1 is the most important in processes.

Metabolic deregulation is an hallmark of many cancers. There is higher lipogenesis de novo and desaturation of saturated fatty acids to meet higher metabolic needs.

In many cancers, there is a higher expression of stearoyl-CoA-1 gene. Stearoyl-CoA-1 contributes to cancer cell proliferation and inhibition of apoptosis, promoting cancer growth.

This reason leads to effort for the development of anticancer drugs. Such anticancer drugs are targeted to inhibit SCD-1.

Stearoyl-CoA-1 plays also important role in pathogenesis of metabolic diseases like diabetes mellitus type 2, obesity, fatty liver disease and atherosclerosis. Inhibition of SCD-1 improves insulin sensitivity, decreases lipid content in hepatocytes and reduces adipose tissue.

For these reasons, some available inhibitors of SCD-1 are tested as a new therapeutic agents for treatment of fatty liver disease, obesity or diabetes mellitus type 2. Aramchol, a conjugate of cholic and fatty acid, is very promising in treatment of fatty liver disease.

Despite these facts, there are some controversies. Treatment targeted on inhibition of SCD-1 has not only the beneficial effects but also some adverse effects.

It was proved that in mice the inhibitors of SCD-1 should worsen the atherosclerosis. There is a needed for more studies to elucidate an effect of influence of SCD-1 in diseases.