High fat diet induces ceramide and sphingomyelin formation in rat’s liver nuclei

Chocian, Grzegorz; Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata; Harasim, Ewa; Łukaszuk, Bartłomiej; Górski, Jan

doi:10.1007/s11010-010-0409-6

Cited by 72 publications

(64 citation statements)

References 48 publications

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“…This results, thereby, indicate that an enhancement in the content of CER was a consequence of increased formation of the compound from sphingomyelin. It seems that hyperthyroidism may increase activity of acidic SMase, which in turn elevates CER level, as has been reported for liver tissue homogenates, cultured hepatocytes [38] as well as in the adipose tissue of ob/ob mice [39] and high fat diet induced obesity in rodent models [40]. On the other hand, the present study also demonstrated that hyperthyroidism expressively increased sphingomyelin level.…”

Section: Discussionsupporting

confidence: 87%

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Mikłosz

Łukaszuk

Chabowski

et al. 2015

Cell Physiol Biochem

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Background: Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Methods: Male Wistar rats were treated for 10 days with triiodothyronine (T₃) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. Results: We have demonstrated that prolonged, in vivo, T₃ treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). Conclusions: We conclude that prolonged T₃ treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.

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Section: Discussionsupporting

confidence: 87%

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Mikłosz

Łukaszuk

Chabowski

et al. 2015

Cell Physiol Biochem

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“…CER is synthesized from serine and palmitoyl-CoA or hydrolysis of SM by acid sphingomyelinase (ASM). HFD is known to increase CER and SM in liver [64]. The present observation of decreased SM and CER levels in HFD-fed CYP7A1-tg mice indicated that bile acids might reduce HFD-induced increase of SM and CER.…”

Section: Discussionmentioning

confidence: 47%

Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice

Jiang

Cheng

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

173

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Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and diabetes. However the mechanism of resistance to HFD-induced obesity of CYP7A1-tg mice has not been determined. In this study, metabolomic and lipidomic profiles of CYP7A1-tg mice were analyzed to explore the metabolic alterations in CYP7A1-tg mice that govern the protection against obesity and insulin resistance by using ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry combined with multivariate analyses. Lipidomics analysis identified seven lipid markers including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides that were significantly decreased in serum of HFD-fed CYP7A1-tg mice. Metabolomics analysis identified 13 metabolites in bile acid synthesis including taurochenodeoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, taurocholic acid, and tauro-β-muricholic acid (T-β-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-β-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12α-hydroxylated bile acids and increasing intestinal T-β-MCA may reduce high fat diet-induced increase of phospholipids, sphingomyelins and ceramides, and ameliorate diabetes and obesity.

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“…1). Interestingly, the abundance and/or activity of either neutral or acid sphingomyelinases has been reported to be elevated in the adipose tissue of ob/ob and high-fat diet-induced obese mice as well as in liver in response to high-fat feeding [38,78,79]. Furthermore, a recent study demonstrated that exposure of C2C12 myotubes to exogenous sphingomyelinase can elevate intracellular ceramide levels; however, effects on insulin sensitivity were not determined in this particular study [80].…”

Section: Influence Of Caveolae In Mediating the Effects Of Ceramidementioning

confidence: 86%

Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance

Lipina

Hundal

2011

Diabetologia

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Obesity is a major risk factor for a variety of chronic diseases, including diabetes mellitus, and comorbidities such as cardiovascular disorders. Despite recommended alterations in lifestyle, including physical activity and energy restriction, being the foundation of any antiobesity therapy, this approach has so far proved to be of little success in tackling this major public health concern. Because of this, alternative means of tackling this problem are currently being investigated, including pharmacotherapeutic intervention. Consequently, much attention has been directed towards elucidating the molecular mechanisms underlying the development of insulin resistance. This review discusses some of these potential mechanisms, with particular focus on the involvement of the sphingolipid ceramide. Various factors associated with obesity, such as saturated fatty acids and inflammatory cytokines, promote the synthesis of ceramide and other intermediates. Furthermore, studies performed in cultured cells and in vivo associate these sphingolipids with impaired insulin action. In light of this, we provide an account of the research investigating how pharmacological inhibition or genetic manipulation of enzymes involved in regulating sphingolipid synthesis can attenuate the insulin-desensitising effects of these obesity-related factors. By doing so, we outline potential therapeutic targets that may prove useful in the treatment of metabolic disorders.

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High fat diet induces ceramide and sphingomyelin formation in rat’s liver nuclei

Cited by 72 publications

References 48 publications

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice

Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance

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