Association of Delta-6-Desaturase Expression with Aggressiveness of Cancer, Diabetes Mellitus, and Multiple Sclerosis: A Narrative Review

Abstract

Background: The phosphatidylinositol 3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/ mTOR) signaling regulates multiple cellular processes and organizes cell proliferation, survival, and differentiation with the available nutrients, in particular, fatty acids. Polyunsaturated fatty acids (PUFAs) are cytotoxic to cancer cells and play a critical role in the treatment of multiple sclerosis (MS) and diabetes mellitus (DM). PUFAs are produced in the body by desaturases and elongases from dietary essential fatty acids (EFAs), primarily involving delta-6-desaturase (D6D). D6D is a rate-limiting enzyme for maintaining many aspects of lipid homeostasis and normal health. D6D is important to recognize the mechanisms that regulate the expression of this enzyme in humans. A lower level of D6D was seen in breast tumors compared to normal tissues. Interestingly, the elevated serum level of D6D was seen in MS and DM, which explains the critical role of D6D in inflammatory diseases. Methods: We searched databases of PubMed, Web of Science (WOS), Google Scholar, Scopus and related studies by predefined eligibility criteria. We assessed their quality and extracted data. Results: Regarding the mTOR signaling pathway, there is remarkable contributions of many inflammatory diseases to attention to common metabolic pathways are depicted. Of course, we need to have the insights into each disorder and their pathological process. The first step in balancing the intake of EFAs is to prevent the disruption of metabolism and expression of the D6D enzyme. Conclusions: The ω6 and ω3 pathways are two major pathways in the biosynthesis of PUFAs. In both of these, D6D is a vital bifunctional enzyme desaturating linoleic acid or alpha-linolenic acid. Therefore, if ω6 and ω3 EFAs are given together in a ratio of 2: 1, the D6D expression will be down-regulated and normalized.

Keywords: Cancer; Delta-6-Desaturase; Diabetes Mellitus; mTOR; Multiple sclerosis.

Figure 1

Metabolic Pathway of Polyunsaturated Fatty Acids

Figure 2

Metabolic and immunologic pathway underling mTOR signaling