Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice
The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1−/− mouse model, we tested t...
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doaj-ff2bf6d50dee41bfb53d78d782f2254a2021-04-28T06:01:39ZengElsevierJournal of Lipid Research0022-22752010-08-0151822022210Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient micePawel Dobrzyn0Agnieszka Dobrzyn1Makoto Miyazaki2James M. Ntambi3Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, PolandTo whom correspondence should be addressed. (A.D.); (J.M.N.); Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, PolandDivisions of Renal Diseases and Hypertension and Endocrinology, Metabolism and Diabetes, University of Colorado at Denver and Health Sciences Center, Denver, COTo whom correspondence should be addressed. (A.D.); (J.M.N.); Departments of Biochemistry, University of Wisconsin-Madison, Madison, WI; Nutritional Sciences, University of Wisconsin-Madison, Madison, WIThe heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA 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 deficiency. 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 β-oxidation is also significantly lower in the heart of ob/ob;SCD1−/− mice compared with ob/ob controls. Moreover, SCD1 deficiency 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 SCD1 deficiency.http://www.sciencedirect.com/science/article/pii/S0022227520370565heart steatosisapoptosisceramideleptin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pawel Dobrzyn Agnieszka Dobrzyn Makoto Miyazaki James M. Ntambi |
spellingShingle |
Pawel Dobrzyn Agnieszka Dobrzyn Makoto Miyazaki James M. Ntambi Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice Journal of Lipid Research heart steatosis apoptosis ceramide leptin |
author_facet |
Pawel Dobrzyn Agnieszka Dobrzyn Makoto Miyazaki James M. Ntambi |
author_sort |
Pawel Dobrzyn |
title |
Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice |
title_short |
Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice |
title_full |
Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice |
title_fullStr |
Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice |
title_full_unstemmed |
Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice |
title_sort |
loss of stearoyl-coa desaturase 1 rescues cardiac function in obese leptin-deficient mice |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2010-08-01 |
description |
The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA 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 deficiency. 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 β-oxidation is also significantly lower in the heart of ob/ob;SCD1−/− mice compared with ob/ob controls. Moreover, SCD1 deficiency 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 SCD1 deficiency. |
topic |
heart steatosis apoptosis ceramide leptin |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520370565 |
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