Identification and Characterization of Murine SCD4, a Novel Heart-specific Stearoyl-CoA Desaturase Isoform Regulated by Leptin and Dietary Factors

Miyazaki, Masaru; Jacobson, Mark J.; Man, Weng Chi; Cohen, Paul; Asilmaz, Esra; Friedman, Jeffrey M.; Ntambi, James M.

doi:10.1074/jbc.m304724200

Cited by 182 publications

(139 citation statements)

References 32 publications

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“…More than one isoform of D6d were found in Mucor rouxii by Na-Ranong et al (2006) and in rats by Skrzypski et al (2009). The presence of several SCD isoforms, their tissue-specific distribution and regulation also has been previously reported in mice and rats (Thiede et al, 1986;Miyazaki et al, 2003). The number of D6d isoforms in ruminants remains unclear.…”

Section: Discussionmentioning

confidence: 85%

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Herdmann

Nuernberg

Martin

et al. 2010

Animal

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This study investigated the effects of dietary linolenic acid (C18:3n-3) v. linoleic acid (C18:2n-6) on fatty acid composition and protein expression of key lipogenic enzymes, acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase (SCD) and delta 6 desaturase (Δ6d) in longissimus muscle and subcutaneous adipose tissue of bulls. Supplementation of the diet with C18:3n-3 was accompanied by an increased level of n-3 fatty acids in muscle which resulted in decrease of n-6/n-3 ratio. The diet enriched with n-3 polyunsaturated fatty acids (PUFAs) significantly inhibited SCD protein expression in muscle and subcutaneous adipose tissue, and reduced the Δ6d expression in muscle. There was no significant effect of the diet on ACC protein expression. Inhibition of the Δ6d expression was associated with a decrease in n-6 PUFA level in muscles, whereas repression of SCD protein was related to a lower oleic acid (C18:1 cis-9) content in the adipose tissue. Expression of ACC, SCD and Δ6d proteins was found to be relatively higher in subcutaneous adipose tissue when compared with longissimus muscle. It is suggested that dietary manipulation of fatty acid composition in ruminants is mediated, at least partially, through the regulation of lipogenic enzymes expression and that regulation of the bovine lipogenic enzymes expression is tissue specific.

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Section: Discussionmentioning

confidence: 85%

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Herdmann

Nuernberg

Martin

et al. 2010

Animal

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“…The DesA3 activity assay was similar to an SCD activity assay (31). The reaction mixture contained 20 mM of potassium phosphate and 150~250 mM of NaCl in a total reaction volume of 200 μL.…”

Section: Desaturation Assaymentioning

confidence: 99%

Identification of Rv3230c as the NADPH Oxidoreductase of a Two-Protein DesA3 Acyl-CoA Desaturase inMycobacterium tuberculosisH37Rv

Chen

Fox

2006

Biochemistry

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DesA3 is a membrane-bound stearoyl-CoA Δ9 desaturase that produces oleic acid, a precursor of mycobacterial membrane phospholipids and triglycerides. DesA3 has sequence homology with other membrane desaturases including the presence of the eight His motif proposed to bind the diiron center active site. This family of desaturases function as multi-component complexes, and thus require electron transfer proteins for efficient catalytic turnover. Here we present evidence that Rv3230c from Mycobacterium tuberculosis H37Rv is a biologically relevant electron transfer partner for DesA3 from the same pathogen. For these studies, Rv3230c was expressed as a partially soluble protein in Escherichia coli; recombinant DesA3 was expressed in Mycobacterium smegmatis as a catalytically active membrane protein. The addition of E. coli lysates containing Rv3230c to lysates of M. smegmatis expressing DesA3 gave strong conversion of [1-14 C]-18:0-CoA to [1-14 C]-cis-Δ 9 -18:1-CoA and of [1-14 C]-16:0-CoA to [1-14 C]-cis-Δ 9 -16:1-CoA. Both M. tuberculosis proteins were required to reconstitute activity, as various combinations of control lysates lacking either Rv3230c or DesA3 gave minimal or no activity. Furthermore, the specificity of interaction between Rv3230c and DesA3 was implied by the inability of other related redox systems to substitute for Rv3230c. The reconstituted activity was dependent upon the presence of NADPH, could be saturated by increasing the amount of Rv3230c added and was also sensitive to the salt concentration in the buffer. The results are consistent with the formation of a protein-protein complex, possibly with electrostatic character. This work defines a multi-protein, acyl-CoA desaturase complex from M. tuberculosis H37Rv to minimally consist of a soluble Rv3230c reductase and integral membrane DesA3 desaturase. Further implications of this finding relative to the properties of other multi-protein iron enzyme complexes are discussed.Mycobacterium tuberculosis is a human pathogen that causes one of the world's deadliest diseases, tuberculosis (TB 1 ). Current estimates are that up to one-third of the world's population may be infected with M. tuberculosis and that over two million people die from TB-related diseases each year (1-4). TB has resurged, in part due to the appearance of multipledrug-resistant strains. Consequently, the development of new drugs and the reexamination of drugs formerly deemed effective have become major focuses of world-wide TB research (3)(4)(5). This intense effort has included genome sequencing (6), proteome functional analysis by micro-array approaches (7-11), the TB Protein Structure Initiative [(12), * To whom correspondence should be addressed: Department of Biochemistry, 433 Babcock Drive, Madison, WI 53706. Telephone: (608) . E-mail: bgfox@biochem.wisc.edu. † This work was supported by the National Institutes of Health Grant R01 GM-50853 to B.G.F.1 Abbreviations: AlkB, alkane ω-hydroxylase; DesA3, product of Mycobacterium tuberculosis H37Rv gene rv3229c, a...

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“…Scd1 and Scd2 expression is observed in a variety of lipogenic tissues, including liver and adipose tissue, Scd3 is primarily expressed in the skin, Harderian gland and preputial gland, and Scd4 is mainly expressed in the heart [5,6,9]. SCD3 is a palmitoyl-CoA desaturase with minimal desaturase activity towards stearoyl-CoA, while SCD1, SCD2, and SCD4 desaturate both palmitoyl-CoA and stearoylCoA to palmitoleoyl-CoA and oleoyl-CoA, respectively [11].…”

Section: Multiple Isoforms Of Mouse and Human Scdmentioning

confidence: 99%

“…Four SCD isoforms (Scd1-Scd4) have been identified in the mouse, which reside within a 200 kb region of mouse chromosome 19 [6][7][8][9][10]. Scd1 and Scd2 expression is observed in a variety of lipogenic tissues, including liver and adipose tissue, Scd3 is primarily expressed in the skin, Harderian gland and preputial gland, and Scd4 is mainly expressed in the heart [5,6,9].…”

Section: Multiple Isoforms Of Mouse and Human Scdmentioning

confidence: 99%

Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism

Flowers

Ntambi

2008

Current Opinion in Lipidology

367

305

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Purpose of review-Stearoyl-coenzyme A desaturase 1 is a δ-9 fatty acid desaturase that catalyzes the synthesis of monounsaturated fatty acids and has emerged as a key regulator of metabolism. This review evaluates the latest advances in our understanding of the pivotal role of stearoyl-coenzyme A desaturase 1 in health and disease.Recent findings-scd1-deficient mice have reduced lipid synthesis and enhanced lipid oxidation, thermogenesis and insulin sensitivity in various tissues including liver, muscle and adipose tissue due to transcriptional and posttranscriptional effects. These metabolic changes protect scd1-deficient mice from a variety of dietary, pharmacological and genetic conditions that promote obesity, insulin resistance and hepatic steatosis. Stearoylcoenzyme A desaturase 1 is required to guard against dietary unsaturated fat deficiency, leptin deficiency-induced diabetes, and palmitate-induced lipotoxic insults in muscle and pancreatic β-cells. Paradoxical observations of increased muscle stearoyl-coenzyme A desaturase 1 during obesity, starvation and exercise raise questions as to the role of stearoyl-coenzyme A desaturase 1 in this tissue. Mice with a liverspecific loss of stearoyl-coenzyme A desaturase 1, and inhibition of stearoyl-coenzyme A desaturase 1 via antisense or RNA interference, recapitulate only a subset of the phenotypes observed in global Scd1 deficiency, indicating the involvement of multiple tissues.Summary-Recent studies in humans and animal models have highlighted that modulation of stearoyl-coenzyme A desaturase 1 activity by dietary intervention or genetic manipulation strongly influences several facets of energy metabolism to affect susceptibility to obesity, insulin resistance, diabetes and hyperlipidemia.

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Identification and Characterization of Murine SCD4, a Novel Heart-specific Stearoyl-CoA Desaturase Isoform Regulated by Leptin and Dietary Factors

Cited by 182 publications

References 32 publications

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Identification of Rv3230c as the NADPH Oxidoreductase of a Two-Protein DesA3 Acyl-CoA Desaturase inMycobacterium tuberculosisH37Rv

Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism

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