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