Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

Kersten, Sander

doi:10.1155/2008/132960

Cited by 117 publications

(95 citation statements)

References 124 publications

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“…The plasma TG-lowering action of fibrates is primarily achieved via augmentation of plasma TG clearance, although there is in vivo and in vitro evidence that PPAR␣ agonists also lower VLDL-TG production, potentially due to induction of PLIN2 and FABP1 and subsequent storage of TGs in cytosolic lipid droplets (51)(52)(53)(54). Conversely, deletion of PPAR␣ leads to elevated VLDL-TG production (55,56).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

Mattijssen

Georgiadi

Andasarie

et al. 2014

Journal of Biological Chemistry

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Background: PPAR␣ is an important regulator of hepatic lipid metabolism via target gene regulation. Results: HILPDA is regulated by PPAR␣ via an upstream PPRE. Targeted overexpression of HILPDA increases hepatic triglyceride storage via reduction of TG secretion. Conclusion: HILPDA is a novel PPAR␣ target involved in hepatic triglyceride secretion. Significance: HILPDA might be a potential target in the treatment of non-alcoholic fatty liver disease.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

Mattijssen

Georgiadi

Andasarie

et al. 2014

Journal of Biological Chemistry

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“…apo's are regulated also by the nuclear receptors peroxisome proliferator-activated receptors (Ppars) in mammals (reviewed in Ref. 40).…”

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confidence: 99%

Insight into molecular pathways of retinal metabolism, associated with vitellogenesis in zebrafish

Levi

Ziv

Admon

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Levi L, Ziv T, Admon A, Levavi-Sivan B, Lubzens E. Insight into molecular pathways of retinal metabolism, associated with vitellogenesis in zebrafish. Am J Physiol Endocrinol Metab 302: E626 -E644, 2012. First published December 28, 2011; doi:10.1152/ajpendo.00310.2011Retinal is the main retinoid stored in oviparous eggs of fish, amphibians, and reptiles, reaching the oocytes in association with vitellogenins, the yolk precursor proteins. During early presegmentation stages of zebrafish embryos, retinal is metabolized to retinoic acid (RA), which regulates genes involved in cell proliferation, differentiation, and tissue function and is therefore essential for normal embryonic development. While synthesis of vitellogenin and its regulation by 17␤-estradiol (E2) were extensively investigated, pathways for retinal synthesis remain obscure. We determined the expression pattern of 46 candidate genes, aiming at identifying enzymes associated with retinal synthesis, ascertaining whether they were regulated by E2, and finding pathways that could fulfill the demand for retinoids during vitellogenesis. Genes associated with retinal synthesis were upregulated in liver (rdh10, rdh13, sdr) and surprisingly also in intestine (rdh13) and ovary (rdh1, sdr), concomitantly with higher gene expression and synthesis of vitellogenins in liver but also in extrahepatic tissues, shown here for the first time. Vitellogenin synthesis in the ovary was regulated by E 2. Gene expression studies suggest that elevated retinal synthesis in liver, intestine, and ovary also depends on cleavage of carotenoids (by Bcdo2 or Bmco1), but in the ovary it may also be contingent on higher uptake of retinol from the circulatory system (via Stra6) and retinol synthesis from retinyl esters (by Lpl). Decrease in oxidation (by Raldh2 or Raldh3) of retinal to RA and/or degradation of RA (by Cyp26a1) may also facilitate higher hepatic retinal levels. Together, these processes enable meeting the putative demands of retinal for binding to vitellogenins. Bioinformatic tools reveal multiple hormone response elements in the studied genes, suggesting complex and intricate regulation of these processes. extrahepatic vitellogenin synthesis; regulatory response elements; retinoids; carotenoids RETINAL IS THE PREDOMINANT RETINOID in eggs and oocytes of marine fish and some freshwater fish species and may constitute almost the entire pool of retinoids in these eggs. In oviparous eggs of nonmammalian vertebrates such as teleosts, amphibians, and birds, maternally derived retinal is bound via a Schiff-base linkage to vitellogenins (Vtgs) (15, 32, 62, 63, 64, 72 reviewed in 50). The retinal in fish oocytes and eggs consists of several isomers, whereas the all-trans form is the most abundant in zebrafish embryos (15,44). The use of the all-trans isomer of retinal for major retinoid storage is unique to reptiles, anamniotic vertebrates (teleosts and amphibians), and eggs of ascidian (33,34). This is in contrast to higher vertebrates (birds and mammals), where retinol is the...

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“…Pterostilbene has also been reported to have hypolipidemic properties comparable to clinically used fibrate lipid-lowering drugs (Rimando et al, 2005). The targets of fibrate drugs are members of the peroxisome proliferator-activated receptor (PPAR) group of transcription factors, which play a major role in regulating lipoprotein metabolism (Kersten, 2008). Activation of PPARa in mice and humans reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a reduction in plasma triglyceride levels.…”

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confidence: 99%

A Stress-Inducible Resveratrol O-Methyltransferase Involved in the Biosynthesis of Pterostilbene in Grapevine

et al. 2008

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Stilbenes are considered the most important phytoalexin group in grapevine (Vitis vinifera) and they are known to contribute to the protection against various pathogens. The main stilbenes in grapevine are resveratrol and its derivatives and, among these, pterostilbene has recently attracted much attention due both to its antifungal and pharmacological properties. Indeed, pterostilbene is 5 to 10 times more fungitoxic than resveratrol in vitro and recent studies have shown that pterostilbene exhibits anticancer, hypolipidemic, and antidiabetic properties. A candidate gene approach was used to identify a grapevine resveratrol O-methyltransferase (ROMT) cDNA and the activity of the corresponding protein was characterized after expression in Escherichia coli. Transient coexpression of ROMT and grapevine stilbene synthase in tobacco (Nicotiana benthamiana) using the agroinfiltration technique resulted in the accumulation of pterostilbene in tobacco tissues. Taken together, these results showed that ROMT was able to catalyze the biosynthesis of pterostilbene from resveratrol both in vitro and in planta. ROMT gene expression in grapevine leaves was induced by different stresses, including downy mildew (Plasmopara viticola) infection, ultraviolet light, and AlCl 3 treatment.

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Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

Cited by 117 publications

References 124 publications

Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

Insight into molecular pathways of retinal metabolism, associated with vitellogenesis in zebrafish

A Stress-Inducible Resveratrol O-Methyltransferase Involved in the Biosynthesis of Pterostilbene in Grapevine

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