Stearoyl-CoA desaturase, a short-lived protein of endoplasmic reticulum with multiple control mechanisms

Heinemann, Frank; Ozols, Juris

doi:10.1016/s0952-3278(02)00262-4

Cited by 83 publications

(66 citation statements)

References 87 publications

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“…Impaired regulation of SCD1 protein degradation in adipose tissue may also be involved in the increase found in this protein in morbidly obese individuals. SCD1 is a protein for which activity is regulated only by its concentration (34) and that is rapidly degradated (14). According to some studies, the amount of SCD1 protein does not depend just on mRNA expression (16,35).…”

Section: Discussionmentioning

confidence: 99%

Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects

García‐Serrano

Moreno-Santos²,

Garrido‐Sánchez

et al. 2010

Mol Med

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Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects

García‐Serrano

Moreno-Santos²,

Garrido‐Sánchez

et al. 2010

Mol Med

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“…Instead, mRNA expression levels of desaturases in adipose tissue and the corresponding fatty acid ratios were used as estimates of enzyme activity. Since SCD protein undergoes rapid degradation [29], this could suggest that SCD activity is determined primarily by transcription of the gene and hence by SCD mRNA levels. Finally, the present findings are restricted to SCD in subcutaneous adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance

et al. 2007

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Aims/hypothesis Fatty acid desaturases introduce double bonds into growing fatty acid chains. The key desaturases in humans are Δ 5 -desaturase (D5D), Δ 6 -desaturase (D6D) and stearoyl-CoA desaturase (SCD). Animal and human data implicate hepatic desaturase activities in insulin resistance, obesity and dyslipidaemia. However, the role of desaturase activity in adipose tissue is uncertain. We therefore evaluated relationships between adipose mRNA expression, estimated desaturase activities (fatty acid ratios) in adipose tissue and insulin resistance. Methods Subcutaneous adipose tissue mRNA expression of D5D (also known as FADS1), D6D (also known as FADS2) and SCD was determined in 75 individuals representative of the study population of 294 healthy 63-year-old men.Desaturation indexes (product/substrate fatty acid ratios) were generated from adipose tissue fatty acid composition in all individuals. Insulin resistance was defined as the upper quartile of the updated homeostasis model assessment (HOMA-2) index. Results The relevant desaturation indexes (16:1/16:0, 18:1/18:0, 20:4/20:3 and 18:3/18:2) reflected expression of SCD, but not of D5D or D6D in adipose tissue. Insulin-resistant individuals had a higher adipose tissue 18:1/18:0, but not 16:1/16:0 ratio than insulin-sensitive individuals. Individuals with a high adipose tissue 18:1/18:0 ratio were 4.4-fold (95% CI 1.8-11.8) more likely to be insulin resistant [threefold (95% CI 1.1-8.6) after adjustment for waist circumference and plasma triacylglycerol]. In a multiple regression model predicting HOMA-2, the independent effect of the 18:1/18:0 ratio was borderline (p=0.086). Conclusions/interpretation Adipose tissue desaturation indexes of SCD reflect the expression of the gene encoding the enzyme in this tissue. Elevated SCD activity within adipose tissue is closely coupled to the development of insulin resistance. Diabetologia (2008) 51:328-335 Keywords

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“…Another example of fatty acid desaturase whose expression is regulated via post-translational stability has been reported for ⌬9 acyl-coenzyme A desaturases in yeast and rat liver microsomes (reviewed in Ref. 32). Thirtythree N-terminal amino acids of the rat enzyme, exposed to the cytosolic side of the ER membrane, were found to act as a signal for its rapid degradation (33).…”

Section: Discussionmentioning

confidence: 99%

A Temperature-sensitive Mechanism That Regulates Post-translational Stability of a Plastidial ω-3 Fatty Acid Desaturase (FAD8) in Arabidopsis Leaf Tissues

Matsuda

Sakamoto

Hashimoto

et al. 2005

Journal of Biological Chemistry

117

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Trienoic fatty acids (TAs) are the major constituents in plant membrane lipids. In Arabidopsis, two plastidial isozymes of -3 fatty acid desaturase, FAD7 and FAD8, are the major contributors for TA production in leaf tissues. Despite a high degree of structural relatedness, activities of these two isozymes are regulated differentially in response to temperature. Elevated temperatures lead to decreases in leaf TA level due to temperature sensitivity of FAD8 activity. A series of FAD7-FAD8 chimeric genes, each encoding a functional plastidial -3 desaturase, were introduced into the Arabidopsis fad7fad8 double mutant. Constructs with or without a c-Myc epitope tag were tested. Functionality of each chimeric gene in response to temperature was assayed by Northern and Western analyses and by examining the fatty acid composition. All transformants harboring a chimeric gene containing the FAD8-derived C-terminal coding region (44 amino acids) showed a marked decrease in TA level when exposed to high temperature, similarly as transgenic lines complemented with the native form of FAD8. The reduction of TA level was accompanied by a decrease in the amount of -3 desaturase protein but not necessarily by a decrease in its transcript level. Analysis of the decay of c-Myc-tagged products after inhibiting protein synthesis revealed that the FAD8-derived C-terminal region acts in an autoregulatory fashion to destabilize the protein at high temperature. This suggests that the regulation of post-translational stability of FAD8 provides an important regulatory mechanism for modifying its activity in response to temperature, mediating a decrease in TA level at elevated temperatures.Membrane lipids of plant cells are characterized by a high content of polyunsaturated fatty acids. Typically, dienoic and trienoic fatty acids (DAs and TAs, respectively), 1 account for as much as 70% of total fatty acids in leaf and root lipids (1). The abundance of TAs relative to DAs changes in accordance with environmental conditions. In particular, increasing and decreasing in TA levels have been observed in a variety of plant species exposed to low and high temperatures, respectively (2-4). TAs are formed from DAs in the endoplasmic reticulum (ER) and in plastids by -3 fatty acid desaturases (5). In Arabidopsis, FAD3 encodes an ER-localized -3 desaturase (6), whereas FAD7 and FAD8 encode plastidial isozymes of this enzyme (7,8).The physiological relevance of the responses to temperature has been demonstrated in transgenic plants with modified leaf TA contents. For example, FAD7-deficient tobacco plants showed reduced leaf TA levels but performed better regarding growth and photosynthesis at high temperature (9). Thus, regulation of plastidial -3 desaturase activity is likely associated with the adaptation of plants to elevated temperatures.The production of TAs in root tissues depends predominantly on the activity of ER-localized FAD3 desaturase (10). According to previous studies in Arabidopsis and wheat, it is likely that temperature-regulated po...

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Stearoyl-CoA desaturase, a short-lived protein of endoplasmic reticulum with multiple control mechanisms

Cited by 83 publications

References 87 publications

Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects

Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects

Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance

A Temperature-sensitive Mechanism That Regulates Post-translational Stability of a Plastidial ω-3 Fatty Acid Desaturase (FAD8) in Arabidopsis Leaf Tissues

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