Role of stearoyl-CoA desaturase-1 in skeletal muscle function and metabolism

2013 ◽  
Vol 305 (7) ◽  
pp. E767-E775 ◽  
Author(s):  
Alexis D. Stamatikos ◽  
Chad M. Paton
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Skeletal Muscle Function ◽  
Skeletal Muscle Lipid ◽  
Stearoyl Coa Desaturase ◽  
Scd1 Expression

Stearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids (SFA) into monounsaturated fatty acids and is necessary for proper liver, adipose tissue, and skeletal muscle lipid metabolism. While there is a wealth of information regarding SCD1 expression in the liver, research on its effect in skeletal muscle is scarce. Furthermore, the majority of information about its role is derived from global knockout mice, which are known to be hypermetabolic and fail to accumulate SCD1's substrate, SFA. We now know that SCD1 expression is important in regulating lipid bilayer fluidity, increasing triglyceride formation, and enabling lipogenesis and may protect against SFA-induced lipotoxicity. Exercise has been shown to increase SCD1 expression, which may contribute to an increase in intramyocellular triglyceride at the expense of free fatty acids and diacylglycerol. This review is intended to define the role of SCD1 in skeletal muscle and discuss the potential benefits of its activity in the context of lipid metabolism, insulin sensitivity, exercise training, and obesity.

scholarly journals The RabGAPs TBC1D1 and TBC1D4 control uptake of long-chain fatty acids into skeletal muscle via fatty acid transporter SLC27A4/FATP4 Short title: RabGAPs in skeletal muscle lipid metabolism

2020 ◽  
Author(s):  
Ada Admin ◽  
Tim Benninghoff ◽  
Lena Espelage ◽  
Samaneh Eickelschulte ◽  
Isabel Zeinert ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Long Chain Fatty Acids ◽  
Muscle Lipid ◽  
Skeletal Muscle Lipid ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Long Chain

The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4 play a crucial role in the regulation of GLUT4 translocation in response to insulin and contraction in skeletal muscle. In mice, deficiency in one or both RabGAPs leads to reduced insulin and contraction-stimulated glucose uptake, and to elevated fatty acid uptake and oxidation in both glycolytic and oxidative muscle fibers without altering mitochondrial copy number and the abundance of OXPHOS proteins. Here we present evidence for a novel mechanism of skeletal muscle lipid utilization involving the two RabGAPs and the fatty acid transporter SLC27A4/FATP4. Both RabGAPs control the uptake of saturated and unsaturated long-chain fatty acids (LCFAs) into skeletal muscle and knockdown of a subset of RabGAP substrates, <i>Rab8, Rab10 </i>or <i>Rab14, </i>decreased LCFA uptake into these cells. In skeletal muscle from <i>Tbc1d1/Tbc1d4</i> knockout animals, SLC27A4/FATP4 abundance was increased and depletion of SLC27A4/FATP4 but not FAT/CD36 completely abrogated the enhanced fatty acid oxidation in RabGAP-deficient skeletal muscle and cultivated C2C12 myotubes. Collectively, our data demonstrate that RabGAP-mediated control of skeletal muscle lipid metabolism converges with glucose metabolism at the level of downstream RabGTPases and involves regulated transport of LCFAs via SLC27A4/FATP4.

scholarly journals Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 948 ◽  
Author(s):  
Zuzanna Tracz-Gaszewska ◽  
Pawel Dobrzyn
Keyword(s):  
Fatty Acids ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Cancer Aggressiveness ◽  
Wide Range ◽  
Stearoyl Coa Desaturase ◽  
Poor Outcomes

A distinctive feature of cancer cells of various origins involves alterations of the composition of lipids, with significant enrichment in monounsaturated fatty acids. These molecules, in addition to being structural components of newly formed cell membranes of intensely proliferating cancer cells, support tumorigenic signaling. An increase in the expression of stearoyl-CoA desaturase 1 (SCD1), the enzyme that converts saturated fatty acids to ∆9-monounsaturated fatty acids, has been observed in a wide range of cancer cells, and this increase is correlated with cancer aggressiveness and poor outcomes for patients. Studies have demonstrated the involvement of SCD1 in the promotion of cancer cell proliferation, migration, metastasis, and tumor growth. Many studies have reported a role for this lipogenic factor in maintaining the characteristics of cancer stem cells (i.e., the population of cells that contributes to cancer progression and resistance to chemotherapy). Importantly, both the products of SCD1 activity and its direct impact on tumorigenic pathways have been demonstrated. Based on these findings, SCD1 appears to be a significant player in the development of malignant disease and may be a promising target for anticancer therapy. Numerous chemical compounds that exert inhibitory effects on SCD1 have been developed and preclinically tested. The present review summarizes our current knowledge of the ways in which SCD1 contributes to the progression of cancer and discusses opportunities and challenges of using SCD1 inhibitors for the treatment of cancer.

scholarly journals The lipid metabolism in carp during invasion by the tapeworn Bothriocephalus acheilognathi

2020 ◽  
Vol 11 (2) ◽  
pp. 214-219
Author(s):  
L. L. Yuskiv ◽  
I. D. Yuskiv
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Polyunsaturated Fatty Acids ◽  
Lipid Level ◽  
Saturated Fatty Acids ◽  
Total Content ◽  
Total Lipids ◽  
Lower Content ◽  
Bothriocephalus Acheilognathi

The changes in total lipids, their fatty acid composition and the ratio of individual classes were established in tissues of the intestine, hepatopancreas and skeletal muscles of carp (Cyprinus carpio Linnaeus, 1758), with body weight 14.5–20.5 g, at different rates of invasion by Bothriocephalus acheilognathi (Yamaguti, 1934) helminth, which belongs to the family Bothriocephalidae, of the Pseudophyllidae order, of the Cestoda class. The examined carp was divided into three groups: first group of fish was free from intestinal helminths of B. acheilognathi (control); second group of fish was weakly infected with helminths (intensity of invasion is 1–3 helminths per fish); the third group of fish was highly infected (the invasion intensity is 4 worms and more per fish). Our results showed that fish infected with helminth B. acheilognathi compared to uninfected fish had reduced total lipid level in the gut due to phospholipids, triacylglycerols, and also lipids were characterized by lower content of linoleic, linolenic, arachidonic, penta- and hexanoic fatty acids; decrease in the level of unsaturated and increase in the content of saturated fatty acids, which leads to an increase of the saturation factor. During the infection of carp with B. acheilognathi in the hepatopancreas, the content of total lipids, structural lipids – phospholipids and reserve energy sources – triacylglycerols is probably reduced, and lipids are characterized by a high content of saturated fatty acids (С14:0, С16:0, С18:0) and lower content of unsaturated: arachidonic (С20:4), linolenic (С18:3) and linoleic acid (С18:2), which is associated with a decrease in the source for the synthesis of a number of polyunsaturated fatty acids, especially docosahexaenoic (С22:6). The total content of lipids, triacylglycerols, free fatty acids and phospholipids in skeletal muscle of carp during the Bothriocephalus invasion decreased and the content of free cholesterol, mono- and triacylglycerols increased. Helminth B. acheilognathi has the effect of reducing the total lipids of the skeletal muscle content of С18-, С20-, С22-polyunsaturated fatty acids and increasing the content of saturated (С14:0, С16:0, С18:0) and monounsaturated (С16:1, С18:1) fatty acids. The obtained results prove that the parasite B. acheilognathi in the intestine of the carp significantly affects the nutrition processes of the host depending on the intensity of the damage by helminths, which is accompanied by impaired lipid metabolism.

scholarly journals Sequential dynamics of Stearoyl-CoA Desaturase-1(SCD1) /ligand binding and unbinding mechanism: A computational study

2020 ◽  
Author(s):  
Anna B. Petroff ◽  
Rebecca L. Weir ◽  
Charles R. Yates ◽  
Joseph D. Ng ◽  
Jerome Baudry
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Computational Study ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Membrane Composition ◽  
Endoplasmic Reticulum Protein ◽  
Metabolic Protein ◽  
Stearoyl Coa Desaturase ◽  
Dynamic Series

AbstractStearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl-CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as apoprotein. The modeling of SCD1:fatty acid interactions suggests that 1) SCD1:CoA moiety interactions open the substrate binding tunnel, 2) SCD1 stabilizes a substrate conformation favorable for desaturation, and 3) SCD1:product interactions result in an opening of the tunnel, possibly allowing product exit into the surrounding membrane. Together, these results describe a highly dynamic series of SCD1 conformations resulting from the enzyme:cofactor:substrate interplay that inform drug-discovery efforts.

scholarly journals SCD1, autophagy and cancer: implications for therapy

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Francesca Ascenzi ◽  
Claudia De Vitis ◽  
Marcello Maugeri-Saccà ◽  
Christian Napoli ◽  
Gennaro Ciliberto ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Monounsaturated Fatty Acids ◽  
Cellular Functions ◽  
Cancer Heterogeneity ◽  
Intracellular Degradation ◽  
Mutual Regulation ◽  
Key Enzyme ◽  
Proliferation And Metastasis

Abstract Background Autophagy is an intracellular degradation system that removes unnecessary or dysfunctional components and recycles them for other cellular functions. Over the years, a mutual regulation between lipid metabolism and autophagy has been uncovered. Methods This is a narrative review discussing the connection between SCD1 and the autophagic process, along with the modality through which this crosstalk can be exploited for therapeutic purposes. Results Fatty acids, depending on the species, can have either activating or inhibitory roles on autophagy. In turn, autophagy regulates the mobilization of fat from cellular deposits, such as lipid droplets, and removes unnecessary lipids to prevent cellular lipotoxicity. This review describes the regulation of autophagy by lipid metabolism in cancer cells, focusing on the role of stearoyl-CoA desaturase 1 (SCD1), the key enzyme involved in the synthesis of monounsaturated fatty acids. SCD1 plays an important role in cancer, promoting cell proliferation and metastasis. The role of autophagy in cancer is more complex since it can act either by protecting against the onset of cancer or by promoting tumor growth. Mounting evidence indicates that autophagy and lipid metabolism are tightly interconnected. Conclusion Here, we discuss controversial findings of SCD1 as an autophagy inducer or inhibitor in cancer, highlighting how these activities may result in cancer promotion or inhibition depending upon the degree of cancer heterogeneity and plasticity.

The role of saturated fatty acids in impaired lipid metabolism in patients with alcohol dependence syndrome

2020 ◽  
Vol 120 (9) ◽  
pp. 93
Author(s):  
V.A. Solovieva ◽  
S.N. Leichter ◽  
N.V. Solovyova ◽  
F.A. Bichkaeva ◽  
N.S. Ishekov ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Alcohol Dependence ◽  
Saturated Fatty Acids ◽  
Alcohol Dependence Syndrome

Induction of stearoyl-CoA desaturase protects human arterial endothelial cells against lipotoxicity

2008 ◽  
Vol 295 (2) ◽  
pp. E339-E349 ◽  
Author(s):  
Andreas Peter ◽  
Cora Weigert ◽  
Harald Staiger ◽  
Kilian Rittig ◽  
Alexander Cegan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Endothelial Cells ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Hek 293 ◽  
Stearoyl Coa Desaturase ◽  
Arterial Endothelial Cells

Endothelial lipotoxicity has been implicated in the pathogenesis of multiple stages of cardiovascular disease from early endothelial dysfunction to manifest atherosclerosis and its complications. Saturated free fatty acids are the major inducers of endothelial cell apoptosis and inflammatory cytokines. In humans, the enzyme human stearoyl-CoA desaturase-1 (hSCD-1) is the limiting step of the desaturation of saturated to monounsaturated fatty acids. Since we could demonstrate the expression of SCD-1 in primary human arterial endothelial cells (HAECs), we aimed to prove a beneficial role of upregulated hSCD-1 expression. In contrast to other cells that are less susceptible to lipotoxicity, hSCD-1 was not upregulated in HAECs upon palmitate treatment. Following that, we could show that upregulation of hSCD-1 using the LXR activator TO-901317 in HAECs protects the cells against palmitate-induced lipotoxicity, cell apoptosis, and expression of inflammatory cytokines IL-6 and IL-8. Increased hSCD-1 activity was determined as increased C16:1/16:0 ratio and enhanced triglyceride storage in palmitate treated cells. The beneficial effect was clearly attributed to enhanced hSCD-1 activity. Overexpression of hSCD-1 blocked palmitate-induced cytotoxicity, and knockdown of hSCD-1 using siRNA abolished the protective effect of TO-901317 in HEK-293 cells. Additionally, inhibition of hSCD-1 with 10/12 CLA blocked the effect of TO-901317 on palmitate-induced lipotoxicity, cell apoptosis, and inflammatory cytokine induction in HAECs. We conclude that upregulation of hSCD-1 leads to a desaturation of saturated fatty acids and facilitates their esterification and storage, thereby preventing downstream effects of lipotoxicity in HAECs. These findings add a novel aspect to the atheroprotective actions of LXR activators in cardiovascular disease.

scholarly journals Stearoyl-CoA Desaturase Is Essential for Porcine Adipocyte Differentiation

2020 ◽  
Vol 21 (7) ◽  
pp. 2446
Author(s):  
Lulu Liu ◽  
Yu Wang ◽  
Xiaojuan Liang ◽  
Xiao Wu ◽  
Jiali Liu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipocyte Differentiation ◽  
Saturated Fatty Acids ◽  
Critical Role ◽  
Lipid Synthesis ◽  
Growth Efficiency ◽  
Monounsaturated Fatty Acids ◽  
Fat Deposition ◽  
Key Enzyme ◽  
Stearoyl Coa Desaturase

Fat deposition, which influences pork production, meat quality and growth efficiency, is an economically important trait in pigs. Numerous studies have demonstrated that stearoyl-CoA desaturase (SCD), a key enzyme that catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, is associated with fatty acid composition in pigs. As SCD was observed to be significantly induced in 3T3-L1 preadipocytes differentiation, we hypothesized that it plays a role in porcine adipocyte differentiation and fat deposition. In this study, we revealed that SCD is highly expressed in adipose tissues from seven-day-old piglets, compared to its expression in tissues from four-month-old adult pigs. Moreover, we found that SCD and lipogenesis-related genes were induced significantly in differentiated porcine adipocytes. Using CRISPR/Cas9 technology, we generated SCD-/- porcine embryonic fibroblasts (PEFs) and found that the loss of SCD led to dramatically decreased transdifferentiation efficiency, as evidenced by the decreased expression of known lipid synthesis-related genes, lower levels of oil red O staining and significantly lower levels of triglyceride content. Our study demonstrates the critical role of SCD expression in porcine adipocyte differentiation and paves the way for identifying it as the promising candidate gene for less fat deposition in pigs.

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