Investigation of the putative rate‐limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells

Zámbó, Veronika; Simon-Szabó, Laura; Sarnyai, Farkas; Mátyási, Judit; Gór-Nagy, Zsófia; Somogyi, Anna; Szelényi, Péter; Kereszturi, Éva; Tóth, Blanka; Csala, Miklós

doi:10.1002/1873-3468.13622

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…Although double bonds can be formed at various positions up to 9, the first one must be created by a stearoyl-CoA desaturase between the carbons 9 and 10, which makes SCD activity rate determining for the overall desaturation process. It has also been demonstrated that SCD activity is not limited by the capacity of the associated electron transfer chain, so it is determined by the level of SCD enzyme itself [ 25 ]. Among the two human SCDs, SCD1 is highly expressed in most tissues including liver, adipose tissue, heart, lung, and the central nervous system, and its metabolic role is clear, the recently discovered SCD5 is present mostly in the central nervous system and some endocrine and reproductive organs, and its function is obscure [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms Underlying the Elevated Expression of a Potentially Type 2 Diabetes Mellitus Associated SCD1 Variant

Tibori

Orosz

Zámbó

et al. 2022

IJMS

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Disturbances in lipid metabolism related to excessive food intake and sedentary lifestyle are among major risk of various metabolic disorders. Stearoyl-CoA desaturase-1 (SCD1) has an essential role in these diseases, as it catalyzes the synthesis of unsaturated fatty acids, both supplying for fat storage and contributing to cellular defense against saturated fatty acid toxicity. Recent studies show that increased activity or over-expression of SCD1 is one of the contributing factors for type 2 diabetes mellitus (T2DM). We aimed to investigate the impact of the common missense rs2234970 (M224L) polymorphism on SCD1 function in transfected cells. We found a higher expression of the minor Leu224 variant, which can be attributed to a combination of mRNA and protein stabilization. The latter was further enhanced by various fatty acids. The increased level of Leu224 variant resulted in an elevated unsaturated: saturated fatty acid ratio, due to higher oleate and palmitoleate contents. Accumulation of Leu224 variant was found in a T2DM patient group, however, the difference was statistically not significant. In conclusion, the minor variant of rs2234970 polymorphism might contribute to the development of obesity-related metabolic disorders, including T2DM, through an increased intracellular level of SCD1.

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Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms Underlying the Elevated Expression of a Potentially Type 2 Diabetes Mellitus Associated SCD1 Variant

Tibori

Orosz

Zámbó

et al. 2022

IJMS

Self Cite

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SCD1 is the critical signaling hub to mediate metabolic diseases: Mechanism and the development of its inhibitors

Sun,

Xing,

Wang

et al. 2024

Biomedicine & Pharmacotherapy

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A Single Nucleotide Polymorphism (rs3811792) Affecting Human SCD5 Promoter Activity Is Associated with Diabetes Mellitus

Zámbó

Orosz

Szabó

et al. 2022

Genes

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The combined prevalence of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus is 10.5% worldwide and this is constantly increasing. The pathophysiology of the diseases include disturbances of the lipid metabolism, in which acyl-CoA desaturases play a central role as they synthesize unsaturated fatty acids, thereby providing protection against lipotoxicity. The stearoyl-CoA desaturase-5 (SCD5) isoform has received little scientific attention. We aimed to investigate the SCD5 promoter and its polymorphisms in vitro, in silico and in a case-control study. The SCD5 promoter region was determined by a luciferase reporter system in HepG2, HEK293T and SK-N-FI cells and it was proved to be cell type-specific, but it was insensitive to different fatty acids. The effect of the SCD5 promoter polymorphisms rs6841081 and rs3811792 was tested in the transfected cells. The T allele of rs3811792 single nucleotide polymorphism (SNP) significantly reduced the activity of the SCD5 promoter in vitro and modified several transcription factor binding sites in silico. A statistically significant association of rs3811792 SNP with T1DM and T2DM was also found, thus supporting the medical relevance of this variation and the complexity of the molecular mechanisms in the development of metabolic disorders. In conclusion, the minor allele of rs3811792 polymorphism might contribute to the development of diabetes by influencing the SCD5 promoter activity.

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Investigation of the putative rate‐limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells

Cited by 4 publications

References 38 publications

Molecular Mechanisms Underlying the Elevated Expression of a Potentially Type 2 Diabetes Mellitus Associated SCD1 Variant

Molecular Mechanisms Underlying the Elevated Expression of a Potentially Type 2 Diabetes Mellitus Associated SCD1 Variant

SCD1 is the critical signaling hub to mediate metabolic diseases: Mechanism and the development of its inhibitors

A Single Nucleotide Polymorphism (rs3811792) Affecting Human SCD5 Promoter Activity Is Associated with Diabetes Mellitus

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