Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Wang, Xinting; Li, Jingya; Liu, Li; Hu, Nan; Jin, Shi; Liu, Can; Mei, Dan; Liu, Xiaodong

doi:10.1038/aps.2012.50

Cited by 29 publications

(17 citation statements)

References 55 publications

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“…Finally we did not observe changes in cholesterol content in the diabetic heart which supports our conclusion that LXRs were not activated after injection of streptozotocin. Differences between our results and those obtained by Cheng et al [9] and Wang et al [25] might result from different duration of experiments (3-week study vs. 5 or 20-week study) and/or the type of animal model (Wistar rats vs. Sprague Dawley rats).…”

Section: Discussioncontrasting

confidence: 97%

“…Cheng et al [9] and Wang et al [25], found significant increase of ABCA1 and ABCG1 protein levels in the heart of diabetic rats. These transporters are responsible for cholesterol removal from cells [30], and they are under transcriptional regulation by LXRs [31].…”

Section: Discussionmentioning

confidence: 97%

“…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. Moreover, both authors reported elevation of myocardial expression of LXR target genes: FAT/CD36 and acyl-CoA synthetase (ACSL), which are involved in lipid uptake and storage [9], and ATP-binding cassette transporter A1 (ABCA1), which is involved in reduction of cellular cholesterol content [25].…”

Section: Discussionmentioning

confidence: 99%

“…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. Moreover, both authors reported elevation of myocardial expression of LXR target genes: FAT/CD36 and acyl-CoA synthetase (ACSL), which are involved in lipid uptake and storage [9], and ATP-binding cassette transporter A1 (ABCA1), which is involved in reduction of cellular cholesterol content [25]. We also found increase in the level o FAT/ CD36 in the diabetic myocardium, however, mRNA level of other known LXR target genes, SREBP-1c and ACC1 [26], did not increase.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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show abstract

“…A recent study by Wang et al has reported high-cholesterol levels in the STZ-induced rat brain with decreased expression of ApoE mRNA. However, they have observed decreased cholesterol levels and high ABCA1 expressions in peripheral tissues [273]. These results suggest that in case of diabetes, the body tends to decrease cholesterol levels by expressing ABAC1.…”

Section: Linking Lipids With Ad and Diabetesmentioning

confidence: 94%

Metabolic study of Alzheimer’s disease using mutant C. elegans

Ahmad¹

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Alzheimer's disease (AD) is associated with chronic neurodegeneration and is the cause of the most common form of dementia. The main hallmarks of AD are aggregates of amyloid beta (Aβ) and formation of hyperphosphorylated tau neurofibrillary tangles (NFTs). Unfortunately, after more than 100 years of research the exact cause(s) and mechanisms involved in AD progression remain unclarified. Evidence indicates that impaired mitochondrial bioenergetics may precede by decades, the neurodegeneration and cognitive decline associated with AD. Moreover, a genetic association of the core metabolic enzyme dihydrolipoamide dehydrogenase (DLD) with late-onset AD and reduced activity of DLD-containing enzymes suggests glucose hypo-metabolism as a possible cause of AD. Contrary to this, improvements of AD symptoms under caloric restriction or other means of reducing-glucose dependent energy metabolism supports an alternative hypothesis that a decrease in glucose metabolism may be protective. In the present study, we used mutant Caenorhabditis elegans (C. elegans) to investigate the effect of glucose metabolism on AD progression. We initially looked at the role of suppressed DLD-1, and then we focused on the effect of high glucose in AD pathogenesis.Transgenic expression of Aβ in C. elegans causes both phenotypic and behavioral defects and results in accumulation of toxic Aβ oligomers, culminating in protein aggregation as is normally associated with AD pathophysiology. Aβ expression in worm muscle causes agedependent progressive paralysis and impaired acetylcholine neurotransmission while neuronal Aβ expression results in defective chemotaxis and impaired serotonin sensitivity as well as reduced fecundity and egg hatching. Suppression of the dld-1 gene alleviated paralysis, improved acetylcholine neurotransmission, enhanced chemotaxis and restored normal sensitivity to serotonin.dld-1 gene suppression also protects vitality as indicated by improved fecundity and egg hatching.Interestingly, protective effects of dld-1 suppression could be reversed using the calcium ionophore (CaI), indicating that the protective mechanism involves calcium signaling. Each of these beneficial effects of dld-1 gene suppression could be mimicked using a specific, small molecule inhibitor of the DLD-1 enzyme, 5-methoxyindole-2-carboxylic acid (MICA).High glucose levels are associated with the metabolic disorder, diabetes, which is a major risk factor for AD. In fact, it has been suggested that AD is a neural form of diabetes, type 3 diabetes. If true, drugs used to treat diabetes could act as possible treatments for AD. In this study, I investigated the effect of elevated glucose, the glucose metabolism inhibitor, 2-deoxy-d-glucose ii (2DOG) as well as the anti-diabetes drugs, metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on AD progression. Elevated glucose in the growth medium induced hyperactivity, which interfered with the paralysis assays, but it was seen to impair cholinergic neurotransmission, egg laying and hatc...

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