Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart

Dobrzyń, Paweł; Sampath, Harini; Dobrzyń, Agnieszka; Miyazaki, Masaru; Ntambi, James M.

doi:10.1152/ajpendo.00471.2007

Cited by 71 publications

(72 citation statements)

References 43 publications

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“…To clarify possible mechanisms of TG accumulation in the kidney, we examined the expression of enzymes that are key regulators of FA metabolism (SCD1) (19)(20)(21), increased uptake (CD36), and decreased expression of enzymes of fat ␤ -oxidation (ACO and CPT1). The expressions of PPAR ␣ and PPAR ␦ and their downstream enzymes ACO and CPT1 were decreased and correlated with the decline in eGFR ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy

Herman‐Edelstein

Scherzer

Tobar

et al. 2014

Journal of Lipid Research

455

416

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Section: Discussionmentioning

confidence: 99%

Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy

Herman‐Edelstein

Scherzer

Tobar

et al. 2014

Journal of Lipid Research

455

416

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“…Our recent study showed that the lack of SCD1 decreases FA uptake and oxidation while increasing glucose transport and oxidation in the heart ( 15 ). This shift in cardiac substrate utilization from FA to glucose is caused by upregulation of insulin signaling, decreased FA availability, and reduced expression of FA oxidation genes in the heart ( 15 ). Also, lipogenesis is decreased in the heart of SCD1 Ϫ / Ϫ mice, which is accompanied by a reduction in intracellular FA and triglyceride (TG) content ( 15 ).…”

Section: Scd Activity Assaymentioning

confidence: 95%

“…Three isoforms of SCD are expressed and regulated in a hormone-dependent fashion in the heart ( 14 ), the molecular and metabolic implications of which are practically unknown. Our recent study showed that the lack of SCD1 decreases FA uptake and oxidation while increasing glucose transport and oxidation in the heart ( 15 ). This shift in cardiac substrate utilization from FA to glucose is caused by upregulation of insulin signaling, decreased FA availability, and reduced expression of FA oxidation genes in the heart ( 15 ).…”

Section: Scd Activity Assaymentioning

confidence: 99%

“…SCD activity was assayed with 3 M [ 14 C]stearoyl-CoA (American Radiolabeled Chemicals, St. Louis, MO), 2 mM NADH, and 100 g of microsomal protein ( 15 ). After 5 min of incubation, 200 l of 2.5 M KOH in 75% ethanol was added, and the reaction mixture was saponifi ed at 85°C for 1 h. The samples were cooled and acidifi ed with 280 l of formic acid.…”

Section: Scd Activity Assaymentioning

confidence: 99%

“…This shift in cardiac substrate utilization from FA to glucose is caused by upregulation of insulin signaling, decreased FA availability, and reduced expression of FA oxidation genes in the heart ( 15 ). Also, lipogenesis is decreased in the heart of SCD1 Ϫ / Ϫ mice, which is accompanied by a reduction in intracellular FA and triglyceride (TG) content ( 15 ). We have also shown that the activity of SCD is signifi cantly increased in the heart of leptin-defi cient ob/ob mice ( 14 ), characterized by pathologic left ventricular hypertrophy along with elevated TG content and increased myocyte apoptosis ( 5,16 ).…”

Section: Scd Activity Assaymentioning

confidence: 99%

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Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice

Dobrzyń

Miyazaki

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org suggests that cardiac dysfunction, arrhythmias, cardiomyopathy, and congestive heart disease could be direct consequences of obesity and leptin resistance, i.e., fatty acid (FA) overload of cardiomyocytes and lipid accumulation in the heart ( 1, 2 ). Studies performed on humans using magnetic resonance spectroscopy indicate that cardiomyocyte fat correlates well with impaired diastolic fi lling, even in seemingly asymptomatic obese volunteers ( 2 ). One of the proposed reasons is that excess FAs or/and their metabolites, i.e., ceramides, induce apoptosis of cardiomyocytes, which is a direct cause of lipotoxic cardiomyopathy and heart failure ( 2, 3 ). The important role for ceramide-induced apoptosis in obesity-related cardiomyopathies has been shown in many animal models, including leptin-insensitive ZDF rats ( 4 ), leptin-defi cient ob/ob mice ( 5, 6 ), and a mouse model of heart disease induced by cardiomyocyte-specifi c overexpression of acyl-CoA synthase ( 7 ). Many maneuvers that reduce ectopic deposition of lipids, i.e., exercise, caloric restriction, and troglitazone, were shown to signifi cantly improve cardiac function in obesity, which additionally implies that steatosis might be a primary reason for cardiac dysfunction ( 2, 8 ).Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme catalyzing the biosynthesis of monounsaturated FAs and has been shown to be a key regulatory factor of body adiposity ( 9 ). Mice with a targeted disruption in the SCD1 gene have increased energy expenditure and insulin sensitivity and are resistant to diet-induced obesity ( 10, 11 ). SCD1 is involved in regulation of ceramide metabolism. Lack of SCD1 reduces the mRNA level and activity of serAbstract The heart of leptin-defi cient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoylCoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1؊ / ؊ mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin defi ciency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA ␤ -oxidation is also signifi cantly lower in the heart of ob/ ob;SCD1 ؊ / ؊ mice compared with ob/ob controls. Moreover, SCD1 defi ciency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by...

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Raman spectroscopy–based insight into lipid droplets presence and contents in liver sinusoidal endothelial cells and hepatocytes

Szafraniec

Kuś

Wislocka

et al. 2019

Journal of Biophotonics

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Liver sinusoidal endothelial cells (LSECs), a type of endothelial cells with unique morphology and function, play an important role in the liver hemostasis, and LSECs dysfunction is involved in the development of nonalcoholic fatty liver disease (NAFLD). Here, we employed Raman imaging and chemometric data analysis in order to characterize the presence of lipid droplets (LDs) and their lipid content in primary murine LSECs, in comparison with hepatocytes, isolated from mice on high‐fat diet. On NAFLD development, LDs content in LSECs changed toward more unsaturated lipids, and this response was associated with an increased expression of stearylo‐CoA desaturase‐1. To the best of our knowledge, this is a first report characterizing LDs in LSECs, where their chemical composition is analyzed along the progression of NAFLD at the level of single LD using Raman imaging.

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Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart

Cited by 71 publications

References 43 publications

Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy

Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy

Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice

Raman spectroscopy–based insight into lipid droplets presence and contents in liver sinusoidal endothelial cells and hepatocytes

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