Head: Paweł Dobrzyń

Ana Gan
Anna Filip
Tomasz Bednarski
Adam Olichwier
Magda Ghanin
Viktor Navrulin


Research profile:

The emergence of a pandemic of obesity, metabolic syndrome and heart dysfunction has recently became a world-wide problem. Cardiomyocyte steatosis is a main factor in pathogenesis of heart failure associated with obesity. Our research group carries out cutting edge, multidisciplinary studies on signalling and transcriptional cascades that have far-reaching implications on lipid metabolism and human metabolic diseases in obesity- and hypertension-related heart dysfunctions.

Over the last few years, our group identified several important new regulators of cell metabolism. We found that SCD1 deficiency causes a shift in cardiac substrate utilization from fatty acids (FA) to glucose by upregulating insulin signaling, decreasing FA availability, and reducing expression of FA oxidation genes in the heart (Dobrzyn et al. Am J Physiol, 2008). This increase in cardiac insulin sensitivity and glucose utilization due to SCD1 deficiency could prove therapeutic in pathological conditions such as obesity that are characterized by skewed cardiac substrate utilization. We tested this hypothesis using obese leptin-deficient ob/ob mouse model.

We showed that disruption of SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma triglycerides and FA. The improvement was associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac free FA, diacylglycerol, TG and ceramide levels. Moreover, SCD1 deficiency reduced 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 left ventricle function in ob/ob mice caused by SCD1 deficiency (Dobrzyn et al. J Lipid Res, 2010).

Next, we tested the hypothesis that cardiac substrate utilization is affected by oleic acid originating from both the endogenous conversion of stearate and the diet. We show that cardiac SCD1 mRNA and protein are increased in tristearate (TS)-fed rats when compared with chow-fed rats. Overexpression of SCD1 was associated with a significant elevation of oleate and TG levels within the heart. Increased oleate and TG contents were also observed in the hearts of trioleate (TO)-fed rats, although SCD1 protein and mRNA levels were decreased in the myocardium of these rats when compared with TS- or chow-fed rats. Feeding of TS or TO resulted in increased mitochondrial FA oxidation. Additionally, cardiac glucose uptake was decreased by TS or TO feeding. These results suggest that oleic acid (both dietary and de novo synthesized) affects cardiac energy metabolism. Furthermore, our data show that endogenous synthesis of oleate in the heart can compensate for the deficiency of this fatty acid in the diet (Dobrzyn et al. Mitochondrion, 2012).




Proposed model for the effect of SCD1 gene deletion on heart lipid metabolism and left ventricle function in leptin deficiency. Reduction in myocardial lipid accumulation and inhibition of lipid-induced apoptosis appear to be the main mechanism responsible for improved cardiac function in leptin deficient ob/ob mice caused by lack of SCD1 function.





Read more:

Dobrzyn P, Sampath H, Dobrzyn A, Miyazaki M, Ntambi JM: Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart. Am J Physiol Endocrinol Metab. 2008; 294: E357-364.

Dobrzyn P, Dobrzyn A, Miyazaki M, Ntambi JM: Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice. J Lipid Res. 2010; 51: 2202-2210.

Dobrzyn P, Jazurek M, Dobrzyn A: Stearoyl-CoA desaturase and insulin resistance - What is the molecular switch. Biochim Biophys Acta - Bioenerg. 2010; 1797: 1189-1194.

Dobrzyn P, Pyrkowska A, Jazurek M, Dobrzyn A: Increased availability of endogenous and dietary oleic acid contributes to the upregulation of cardiac fatty acid oxidation. Mitochondrion 2012; 12: 132-137.