Elevated Expression of Liver X Receptor Alpha (LXRα) in Myocardium of Streptozotocin-Induced Diabetic Rats

Cheng, Yi; Liu, Guibo; Pan, Qian; Guo, Shu; Yang, Xianghong

doi:10.1007/s10753-010-9281-5

Cited by 28 publications

(25 citation statements)

References 31 publications

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“…A rat DCM model was induced as described previously (24). In brief, 30 rats were injected intraperitoneally with 60 mg/kg body weight of STZ (Sigma) prepared in 0.1 ml citrate buffer (0.1 mmol/l, pH 4.5) to induce diabetic conditions, while 8 rats received an equal volume of vehicle and served as a non-diabetic group.…”

Section: Induction Of Diabetesmentioning

confidence: 99%

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Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

Cheng¹,

Guo²,

Liu³

et al. 2012

International Journal of Molecular Medicine

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Abstract. Diabetic cardiomyopathy (DCM) is a progressive disease of the heart muscle and the third most common cause of heart failure. In the present study, we evaluated the effects of bone marrow-derived endothelial progenitor cell (EPC) transplantation on the development of DCM in a streptozotocin (STZ)-induced diabetic rat model. Ex vivo generated, characterized and cultivated rat EPCs were identified by flow cytometry of their surface markers. EPCs were transplanted intravenously into rats through the tail vein 6 weeks after they were challenged with STZ and the rats were sacrificed 4 weeks later. Before sacrifice, left ventricular (LV) catheterization was performed to evaluate the cardiac function. Myocardium sections were stained with Masson's trichrome staining to investigate myocardial collagen contents. Fibrosis-, apoptosis-and oxidative stress-related gene expressions were analyzed by western blot analysis. Transplantation of EPCs alleviated the impaired cardiac function associated with diabetes and decreased the collagen volume in diabetic myocardium resulting in improved cardiac function. Furthermore, EPC transplantation decreased the expression of type I collagen, Bax, caspase-3 and p67phox, while increasing the expression of Bcl-2 and manganese superoxide dismutase (MnSOD). Taken together, our results suggest that transplantation of EPCs improved cardiac function in the rat DCM model, likely through inhibition of cardiomyocyte apoptosis and attenuating myocardial fibrosis.

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Section: Induction Of Diabetesmentioning

confidence: 99%

“…Western blot analysis was performed as previously described (24). The hearts were lysed in radioimmunoprecipitation (RIPA) assay buffer (Beyotime Institute of Biotechnology, Haimen, China).…”

Section: Induction Of Diabetesmentioning

confidence: 99%

Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

Cheng¹,

Guo²,

Liu³

et al. 2012

International Journal of Molecular Medicine

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“…LXR expression has been identified in human and rodent cardiac tissue [2,5,6,7]. LXRβ is the dominant isoform in the heart of mice [2,5,8].…”

Section: Introductionmentioning

confidence: 99%

LXR Agonist T0901317-Induced Hyperlipidemia Does Not Lead to Lipid Accumulation in the Rat Heart

Harasiuk¹,

Baranowski²,

Zabielski³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Liver X receptors (LXRα and LXRβ) are ligand-activated transcription factors that regulate expression of genes involved in lipid and cholesterol metabolism. LXR expression has been identified in human and rodent cardiac tissue, however, its role in this tissue remains unclear. The aim of this study was to investigate effects of in vivo LXR activation on lipid metabolism in the rat myocardium under the conditions of low and high lipid intake. Methods: The experiments were performed on male Wistar rats fed for 5 weeks on either low fat diet (LFD) or high fat diet (HFD). Next, the animals were randomly divided into two groups receiving either LXR agonist - T0901317 (10mg/kg/d) or vehicle for the last week of the experiment. After anesthesia samples of the left ventricle and blood were taken. Results: It was found that LXRβ is the dominant isoform in the rat myocardium and the expression of both LXR isoforms did not change after administration of T0901317. Agonist treatment induced hyperlipidemia in low fat fed rats and this effect was amplified in high fat fed rats. LXR agonist elevated content of myocardial triacylglycerols in animals fed on LFD and content of phospholipids in animals fed on HFD. Levels of the remaining examined lipid classes (nonesterified fatty acids, diacylglycerol, free cholesterol, cholesterol esters, ceramide) was decreased or unchaged after LXR activation. Conclusion: We conclude that administration of T0901317 does not lead to severe myocardial lipid accumulation in rats despite of its high plasma availability.

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“…This is in contrast to the results obtained by other authors. Cheng et al [9] showed that during the 20-week study, LXRα expression gradually increased in the ventricles and atria of STZ-diabetic rats. Wang et al [25] observed that 5 weeks after injection of streptozotocin mRNA expression of both LXR isoforms was markedly enhanced in the rat heart.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, synthetic LXR agonists stimulate hepatic lipogenesis by induction of expression of SREBP-1c, which results in liver steatosis and hypertriglyceridemia [6,7]. LXR expression has been identified also in the rodent cardiac tissue, and LXRβ is the dominant isoform [2,[8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Liver X Receptor Agonist TO901317 Prevents Diacylglycerols Accumulation in the Heart of Streptozotocin-Diabetic Rats

Harasiuk

Baranowski²,

Zabielski³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Liver X receptors (LXRα and LXRβ) are ligand-activated transcription factors that regulate expression of genes involved in lipid and cholesterol metabolism. LXR expression has been identified in the heart, and enhanced LXR activity in the streptozotocin (STZ) diabetic myocardium was reported recently. The aim of this study was to investigate effect of in vivo LXR activation on myocardial lipid metabolism under conditions of STZ-induced diabetes. Methods: Wistar rats were randomly divided into three experimental groups: non-diabetic control, treated with STZ, and treated with STZ and LXR agonist - TO901317. Diabetes was induced by a single intraperitonal injection of STZ at a dose of 55 mg/kg. LXR agonist was administrated once daily in the morning by an oral gavage at a dose of 10 mg/kg/d during the last week of the experiment. After anesthesia samples of blood and the left ventricle were taken. Results: TO901317 administration increased expression of both LXR isoforms and its target genes: sterol response element binding protein 1c (SREBP-1c) and acetyl-coenzyme A carboxylase 1 (ACC1) in the heart of streptozotocin-diabetic rats. Treatment with LXR agonist had no effect on plasma lipids and glucose in the diabetic rats. Concomitantly, content of the examined lipid classes in the diabetic heart (nonesterified fatty acids, triacylglycerols, phospholipids, cholesterol esters, ceramide) was unchanged after treatment with TO901317. On the contrary, myocardial level of cholesterol and diacylglycerols (DAG) was decreased after LXR activation in diabetic rats, the change in DAG level was associated with downregulated expression of adipose triglyceride lipase (ATGL). Conclusion: Activation of LXRs by TO901317 protects cardiomyocytes against DAG accumulation and thus may reverse disturbances in lipid metabolism observed in streptozotocin-diabetic heart.

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Elevated Expression of Liver X Receptor Alpha (LXRα) in Myocardium of Streptozotocin-Induced Diabetic Rats

Cited by 28 publications

References 31 publications

Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

LXR Agonist T0901317-Induced Hyperlipidemia Does Not Lead to Lipid Accumulation in the Rat Heart

Liver X Receptor Agonist TO901317 Prevents Diacylglycerols Accumulation in the Heart of Streptozotocin-Diabetic Rats

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