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Citations to this article

Critical role of stearoyl-CoA desaturase–1 (SCD1) in the onset of diet-induced hepatic insulin resistance
Roger Gutiérrez-Juárez, … , Brett P. Monia, Luciano Rossetti
Roger Gutiérrez-Juárez, … , Brett P. Monia, Luciano Rossetti
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1686-1695. https://doi.org/10.1172/JCI26991.
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Research Article Metabolism Article has an altmetric score of 26

Critical role of stearoyl-CoA desaturase–1 (SCD1) in the onset of diet-induced hepatic insulin resistance

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Abstract

Stearoyl-CoA desaturase–1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids from saturated fatty acids. Mice with a targeted disruption of Scd1 gene locus are lean and display increased insulin sensitivity. To examine whether Scd1 activity is required for the development of diet-induced hepatic insulin resistance, we used a sequence-specific antisense oligodeoxynucleotide (ASO) to lower hepatic Scd1 expression in rats and mice with diet-induced insulin resistance. Treatment of rats with Scd1 ASO markedly decreased liver Scd1 expression (~80%) and total Scd activity (~50%) compared with that in rats treated with scrambled ASO (control). Insulin clamp studies revealed severe hepatic insulin resistance in high-fat–fed rats and mice that was completely reversed by 5 days of treatment with Scd1 ASO. The latter treatment decreased glucose production (by ~75%), gluconeogenesis, and glycogenolysis. Downregulation of Scd1 also led to increased Akt phosphorylation and marked decreases in the expression of glucose-6-phosphatase (Glc-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Thus, Scd1 is required for the onset of diet-induced hepatic insulin resistance.

Authors

Roger Gutiérrez-Juárez, Alessandro Pocai, Claudia Mulas, Hiraku Ono, Sanjay Bhanot, Brett P. Monia, Luciano Rossetti

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Lipids 2010
Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats[S]
XX Chang, HM Yan, J Fei, MH Jiang, HG Zhu, DR Lu, X Gao
Journal of lipid research 2010
Gum Guar fiber associated with fructose reduces serum triacylglycerol but did not improve the glucose tolerance in rats
CS Motoyama, MJ Pinto, FS Lira, EB Ribeiro, CM do Nascimento, LM Oyama
Diabetology & metabolic syndrome 2010
Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis
JM Brown, S Chung, JK Sawyer, C Degirolamo, HM Alger, TM Nguyen, X Zhu, MN Duong, AL Brown, C Lord, R Shah, MA Davis, K Kelley, MD Wilson, J Madenspacher, MB Fessler, JS Parks, LL Rudel
Arteriosclerosis, thrombosis, and vascular biology 2009
Skin-specific deletion of stearoyl-CoA desaturase-1 alters skin lipid composition and protects mice from high fat diet-induced obesity
H Sampath, MT Flowers, X Liu, CM Paton, R Sullivan, K Chu, M Zhao, JM Ntambi
The Journal of biological chemistry 2009
Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase
ZZ Li, M Berk, TM McIntyre, AE Feldstein
The Journal of biological chemistry 2009
Susceptibility of pancreatic beta cells to fatty acids is regulated by LXR/PPARalpha-dependent stearoyl-coenzyme A desaturase
KH Hellemans, JC Hannaert, B Denys, KR Steffensen, C Raemdonck, GA Martens, PP van Veldhoven, JA Gustafsson, D Pipeleers
PloS one 2009
Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice
M Miyazaki, H Sampath, X Liu, MT Flowers, K Chu, A Dobrzyn, JM Ntambi
Biochemical and Biophysical Research Communications 2009
Despite Antiatherogenic Metabolic Characteristics, SCD1-Deficient Mice Have Increased Inflammation and Atherosclerosis
ML MacDonald, M van Eck, RB Hildebrand, BW Wong, N Bissada, P Ruddle, A Kontush, H Hussein, MA Pouladi, MJ Chapman, C Fievet, TJ van Berkel, B Staels, BM McManus, MR Hayden
Arteriosclerosis, thrombosis, and vascular biology 2009
High fat feeding induces hepatic fatty acid elongation in mice
MH Oosterveer, TH van Dijk, UJ Tietge, T Boer, R Havinga, F Stellaard, AK Groen, F Kuipers, DJ Reijngoud
PloS one 2009
Oleic acid directly regulates POMC neuron excitability in the hypothalamus
YH Jo, Y Su, R Gutierrez-Juarez, S Chua
Journal of neurophysiology 2009
Transcriptional changes associated with reduced spontaneous liver tumor incidence in mice chronically exposed to high dose arsenic
GM Nelson, GJ Ahlborn, JW Allen, H Ren, JC Corton, MP Waalkes, KT Kitchin, BA Diwan, G Knapp, DA Delker
Toxicology 2009
Down-regulation of hepatic stearoyl-CoA desaturase 1 expression by angiotensin II receptor blocker in the obese fa/fa Zucker rat: possible role in amelioration of insulin resistance and hepatic steatosis
J Yokozawa, T Sasaki, K Ohwada, Y Sasaki, JI Ito, T Saito, S Kawata
Journal of Gastroenterology 2009
Effect of trans8, cis10+cis9, trans11 Conjugated Linoleic Acid Mixture on Lipid Metabolism in 3T3-L1 Cells
SV Joseph, JR Miller, RS McLeod, H Jacques
Lipids 2009
Metabolic consequences of sleep-disordered breathing.
Jun J, Polotsky VY
ILAR journal / National Research Council, Institute of Laboratory Animal Resources 2009
Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: Lessons from genetically engineered mice
Catherine Postic*1,2 and Jean Girard1,2
Journal of Clinical Investigation 2008
Inhibition of stearoyl-coenzyme A desaturase 1 dissociates insulin resistance and obesity from atherosclerosis
JM Brown, S Chung, JK Sawyer, C Degirolamo, HM Alger, T Nguyen, X Zhu, MN Duong, AL Wibley, R Shah, MA Davis, K Kelley, MD Wilson, C Kent, JS Parks, LL Rudel
Circulation 2008
Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance
KL Stanhope, PJ Havel
Current Opinion in Lipidology 2008
Elevated hepatic fatty acid elongase-5 activity affects multiple pathways controlling hepatic lipid and carbohydrate composition
Y Wang, M Torres-Gonzalez, S Tripathy, D Botolin, B Christian, DB Jump
Journal of lipid research 2008
Dyslipidemia and Atherosclerosis Induced by Chronic Intermittent Hypoxia Are Attenuated by Deficiency of Stearoyl Coenzyme A Desaturase
V Savransky, J Jun, J Li, A Nanayakkara, S Fonti, AB Moser, KE Steele, MA Schweitzer, SP Patil, S Bhanot, AR Schwartz, VY Polotsky
Circulation research 2008
Stearoyl-Coenzyme A Desaturase 1 Gene Expression Increases after Pioglitazone Treatment and Is Associated with Peroxisomal Proliferator-Activated Receptor-γ Responsiveness
A Yao-Borengasser, N Rassouli, V Varma, AM Bodles, N Rasouli, R Unal, B Phanavanh, G Ranganathan, RE McGehee, PA Kern
The Journal of clinical endocrinology and metabolism 2008
Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism
MT Flowers, JM Ntambi
Current Opinion in Lipidology 2008
Liver TAG Transiently Decreases While PL n-3 and n-6 Fatty Acids are Persistently Elevated in Insulin Resistant Mice
L Scheja, K Toedter, R Mohr, G Niederfellner, MD Michael, A Meissner, A Schoettler, H Pospisil, U Beisiegel, J Heeren
Lipids 2008
Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans
N Stefan, A Peter, A Cegan, H Staiger, J Machann, F Schick, CD Claussen, A Fritsche, HU Häring, E Schleicher
Diabetologia 2008
The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice
NJ de Wit, H Bosch-Vermeulen, PJ de Groot, GJ Hooiveld, MM Bromhaar, J Jansen, M Müller, R der Meer
BMC Medical Genomics 2008
Inhibition of ADRP prevents diet-induced insulin resistance
GM Varela, DA Antwi, R Dhir, X Yin, NS Singhal, MJ Graham, RM Crooke, RS Ahima
American journal of physiology. Gastrointestinal and liver physiology 2008
Compartmentalization of stearoyl-coenzyme A desaturase 1 activity in HepG2 cells
JK Yee, CS Mao, HS Hummel, S Lim, S Sugano, VK Rehan, G Xiao, WN Lee
Journal of lipid research 2008
Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary
AA Sharov, G Falco, Y Piao, S Poosala, KG Becker, AB Zonderman, DL Longo, D Schlessinger, MS Ko
BMC Biology 2008
Genetic Susceptibility to Chronic Hepatitis Is Inherited Codominantly in Helicobacter hepaticus-Infected AB6F1 and B6AF1 Hybrid Male Mice, and Progression to Hepatocellular Carcinoma Is Linked to Hepatic Expression of Lipogenic Genes and Immune Function-Associated Networks
A García, MM Ihrig, RC Fry, Y Feng, S Xu, SR Boutin, AB Rogers, S Muthupalani, LD Samson, JG Fox
Infection and immunity 2008
Hepatic overexpression of glycerol-sn-3-phosphate acyltransferase 1 in rats causes insulin resistance
CA Nagle, J An, M Shiota, TP Torres, GW Cline, ZX Liu, S Wang, RL Catlin, GI Shulman, CB Newgard, RA Coleman
The Journal of biological chemistry 2007
Laminar shear stress up-regulates the expression of stearoyl-CoA desaturase-1 in vascular endothelial cells
X Qin, J Tian, P Zhang, Y Fan, L Chen, Y Guan, Y Fu, Y Zhu, S Chien, N Wang
Cardiovascular Research 2007
Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice
AA Toye, ME Dumas, C Blancher, AR Rothwell, JF Fearnside, SP Wilder, MT Bihoreau, O Cloarec, I Azzouzi, S Young, RH Barton, E Holmes, MI McCarthy, R Tatoud, JK Nicholson, J Scott, D Gauguier
Diabetologia 2007
Probing the role of stearoyl-CoA desaturase–1 in hepatic insulin resistance
MT Flowers, M Miyazaki, X Liu, JM Ntambi
Journal of Clinical Investigation 2006

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