Stearoyl-CoA Desaturase-2 in Murine Development, Metabolism, and Disease.

Lucas M O’Neill,Chang-An Guo,Yar Xin Phang,Zhaojin Liu,James M Ntambi,Sohel Shamsuzzaman,Fang Ding

doi:10.3390/ijms21228619

Abstract

Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis. The MUFAs palmitoleoyl-CoA (16:1n7) and oleoyl-CoA (18:1n9) are the major products of SCD2. Palmitoleoyl-CoA and oleoyl-CoA have various roles, from being a source of energy to signaling molecules. Under normal feeding conditions, SCD2 is ubiquitously expressed and is the predominant SCD isoform in the brain. However, obesogenic diets highly induce SCD2 in adipose tissue, lung, and kidney. Here we provide a comprehensive review of SCD2 in mouse development, metabolism, and various diseases, such as obesity, chronic kidney disease, Alzheimer′s disease, multiple sclerosis, and Parkinson′s disease. In addition, we show that bone mineral density is decreased in SCD2KO mice under high-fat feeding conditions and that SCD2 is not required for preadipocyte differentiation or the expression of PPARγ in vivo despite being required in vitro.

Highlights

Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the de novo synthesis of monounsaturated fatty acids (MUFAs)
SCD2 is required for the survival, development, and de novo synthesis of MUFAs in young mice [14]
We provided a comprehensive review on SCD2 and showed that SCD2KO mice have decreased BMD and BMC when fed a high-fat diet (HFD)

Summary

Introduction

Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the de novo synthesis of monounsaturated fatty acids (MUFAs). The SCD enzymes introduce a single double bond at the ∆9,10 position of long-chain fatty acyl-CoAs that are synthesized de novo or obtained from the diet [1]. The topology of the SCD isoforms consists of four transmembrane domains and three loops connecting them [4]. Both the NH2 and COOH termini are oriented toward the cytosol. To desaturate SFAs, SCD requires NAD(P)H as an electron donor and oxygen as a final electron acceptor. During the process of desaturation, electrons flow from NAD(P)H to cytochrome b5 reductase (FADH2), to cytochrome b5, to SCD, and to O2; which is reduced to H2O [1,5,6]

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Conclusion