Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing β-oxidation in skeletal muscle

University of Dundee, Dundee, Scotland, United Kingdom
AJP Endocrinology and Metabolism (Impact Factor: 3.79). 04/2005; 288(3):E599-607. DOI: 10.1152/ajpendo.00439.2004
Source: PubMed


Stearoyl-CoA desaturase (SCD) has recently been shown to be a critical control point of lipid partitioning and body weight regulation. Lack of SCD1 function significantly increases insulin sensitivity in skeletal muscles and corrects the hypometabolic phenotype of leptin-deficient ob/ob mice, indicating the direct antilipotoxic action of SCD1 deficiency. The mechanism underlying the metabolic effects of SCD1 mutation is currently unknown. Here we show that SCD1 deficiency reduced the total ceramide content in oxidative skeletal muscles (soleus and red gastrocnemius) by approximately 40%. The mRNA levels and activity of serine palmitoyltransferase (SPT), a key enzyme in ceramide synthesis, as well as the incorporation of [14C]palmitate into ceramide were decreased by approximately 50% in red muscles of SCD1-/- mice. The content of fatty acyl-CoAs, which contribute to de novo ceramide synthesis, was also reduced. The activity and mRNA levels of carnitine palmitoyltransferase I (CPT I) and the rate of beta-oxidation were increased in oxidative muscles of SCD1-/- mice. Furthermore, SCD1 deficiency increased phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK activation may be partially responsible for the increased fatty acid oxidation and decreased ceramide synthesis in red muscles of SCD1-/- mice. SCD1 deficiency also reduced SPT activity and ceramide content and increased AMPK phosphorylation and CPT I activity in muscles of ob/ob mice. Taken together, these results indicate that SCD1 deficiency reduces ceramide synthesis by decreasing SPT expression and increasing the rate of beta-oxidation in oxidative muscles.

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Available from: Makoto Miyazaki, Sep 15, 2014
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    • "lated to lipid metabolism, the SCD1 gene is considered a potential factor influencing body weight and obesity (Dobrzyn et al., 2005;Biddinger et al., 2006). In cattle, the SCD1 gene was significantly associated with MUFA content of marbling fat (Taniguchi et al., 2004) and milk production traits (fat and protein content, milk yield) (Macciotta et al., 2008). "
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    ABSTRACT: Stearoyl-CoA desaturase 1 (SCD1) is a critical enzyme that catalyzes the synthesis of monounsaturated fatty acids and is involved in several signaling pathways related to lipid metabolism. The objective of the present study was to estimate the expression of the SCD1 gene in three different ovine tissues strongly associated with lipid homeostasis. The SCD1 gene expression measurement was performed on three tissues (liver, subcutaneous fat, perirenal fat) originated from 15 old-type Polish Merino sheep. The SCD1 transcript abundance was evaluated based on the two most stable endogenous controls (RPS2 – ribosomal protein S2; ATP5G2 – H(+)-transporting ATP synthase). The highest expression of the SCD1 gene was observed in ovine subcutaneous fat compared to perirenal fat and liver. Furthermore, the present research indicated the significant correlation between ovine SCD1 transcript abundance and several important production traits. The expression of the SCD1 gene in liver and perirenal fat highly positively correlated with the feed : gain ratio, test of daily gain and age of the animals at slaughter. Moreover, in both tissues, the SCD1mRNA level positively correlated with weight and content of perirenal fat and subcutaneous fat (R = 0.64, 0.8, 0.6, respectively) and negatively with assessment of external fat content with the use of the EUROP scale (R = −0.64). The SCD1 expression in subcutaneous fat also corresponds with back fat of blade chop and thickness of longissimus dorsi muscles evaluated using USG (ultrasonography) (R = −0.6 and 0.62, respectively). The significant correlation between SCD1 transcript abundance and fattening and slaughtering traits indicate the ability to improve important production traits in sheep via modification of expression of the SCD1 gene.
    Full-text · Dataset · Jan 2016
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    • "Study has shown that SCD1 deficiency increases the rate of β-oxidation in soleus and red gastrocnemius muscles by activating of the AMP-activated protein kinase (AMPK) pathway [34,35]. AMPK leads to phosphorylation and inactivation of acetyl-CoA carboxylase resulting in decreased malonyl-CoA content [36]. "
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    • "We recently described that knock-out mice for SCD-1, and non-transgenic mice treated with a SCD-1 inhibitor, present improved nerve regeneration after peripheral nerve injury (Hussain et al., 2013). Moreover, the products of SCD-1, the mono-unsaturated fatty acids, favor cytotoxic SOD-1 aggregation (Kim et al., 2005), and the accumulation of toxic lipid species such as ceramide (Dobrzyn et al., 2005), suggesting that loss of SCD-1 activity could lower cytotoxicity in ALS. Further work is needed to understand the link between loss of SCD-1 activity and benefits for the motor units, especially in ALS. "
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