Leukotriene B4 Is a Physiologically Relevant Endogenous Peroxisome Proliferator-activated Receptor-α Agonist

Narala, Venkata Ramireddy; Adapala, Ravi K.; Suresh, Madathilparambil V.; Brock, Thomas G.; Peters‐Golden, Marc; Reddy, Raju C.

doi:10.1074/jbc.m109.085118

Cited by 110 publications

(95 citation statements)

References 27 publications

(57 reference statements)

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“…In addition to results obtained in vitro, a recent study has also demonstrated that mice lacking LTB 4 biosynthesis through 5-LO knockout exhibited reduced PPAR␣ activation in response to LPS administration in vivo (Narala et al, 2010). The latter results therefore support the observation that endogenous intracellular LTB 4 formation can reach sufficient concentrations for PPAR␣ activation under inflammatory conditions (Narala et al, 2010).…”

Section: G Other Receptors Involved In Blt Receptor Signalingsupporting

confidence: 72%

“…Subsequent studies using different methods have confirmed LTB 4 binding to and activation of PPAR␣ (Krey et al, 1997;Lin et al, 1999;Narala et al, 2010), although negative results have also been reported (Forman et al, 1997). In addition to results obtained in vitro, a recent study has also demonstrated that mice lacking LTB 4 biosynthesis through 5-LO knockout exhibited reduced PPAR␣ activation in response to LPS administration in vivo (Narala et al, 2010). The latter results therefore support the observation that endogenous intracellular LTB 4 formation can reach sufficient concentrations for PPAR␣ activation under inflammatory conditions (Narala et al, 2010).…”

Section: G Other Receptors Involved In Blt Receptor Signalingsupporting

confidence: 69%

“…In transfected HeLa cells, LTB 4 activated PPAR␣ reporter gene transcription in the micromolar range and bound a fusion protein containing the ligand-binding domain of PPAR␣, with a K d of 90 nM (Devchand et al, 1996). Subsequent studies using different methods have confirmed LTB 4 binding to and activation of PPAR␣ (Krey et al, 1997;Lin et al, 1999;Narala et al, 2010), although negative results have also been reported (Forman et al, 1997). In addition to results obtained in vitro, a recent study has also demonstrated that mice lacking LTB 4 biosynthesis through 5-LO knockout exhibited reduced PPAR␣ activation in response to LPS administration in vivo (Narala et al, 2010).…”

Section: G Other Receptors Involved In Blt Receptor Signalingmentioning

confidence: 94%

See 2 more Smart Citations

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

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Section: G Other Receptors Involved In Blt Receptor Signalingsupporting

confidence: 72%

Section: G Other Receptors Involved In Blt Receptor Signalingsupporting

confidence: 69%

Section: G Other Receptors Involved In Blt Receptor Signalingmentioning

confidence: 94%

See 1 more Smart Citation

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

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“…Wu (80) showed that the induction of fatty acid synthesis and lipogenesis is critical for the survival of KSHV latently infected cells. 5LO is a lipid-metabolizing enzyme (60,81), and LTB4 activates transcription factor NF-B and PPARs, which play significant roles in lipid metabolism and cancer (117). 5LO is an emerging target in obesity, insulin resistance, obesity-related fatty liver disease, metabolic dysfunction (118,119), and nonalcoholic fatty liver and nonalcoholic steatohepatitis (120).…”

Section: Discussionmentioning

confidence: 99%

The Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Induced 5-Lipoxygenase-Leukotriene B4 Cascade Plays Key Roles in KSHV Latency, Monocyte Recruitment, and Lipogenesis

Sharma-Walia

Chandran

Patel

et al. 2014

J Virol

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. 5LO/LTB4 inhibition downregulated TH2-related cytokine secretion, elevated TH1-related cytokine secretion, and reduced human monocyte recruitment, adhesion, and transendothelial migration. 5LO/LTB4 inhibition reduced fatty acid synthase (FASN) promoter activity and its expression. Since FASN, a key enzyme required in lipogenesis, is important in KSHV latency, these findings collectively suggest that 5LO/LTB4 play important roles in KSHV biology and that effective inhibition of the 5LO/LTB4 pathway could potentially be used in treatment to control KS/PEL.

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“…PPARg is also involved in the differentiation of lipid-laden lung fibroblasts, cells that incorporate and accumulate lipids for further provision of lipids to the alveolar type II cells, which produce the surfactant lipids (Chen et al 1998, Rehan & Torday 2012. On the other hand, leukotriene B 4 (LTB 4 ) is an endogenous ligand of PPARa, a PPAR isotype clearly involved in the oxidation of lipids in metabolic tissues (Lefebvre et al 2006, Narala et al 2010. In diabetic pregnancies, PPARa activation negatively regulates lipid content in the fetal liver and the placenta (Martinez et al 2011a,b).…”

Section: Introductionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats

Kurtz¹,

Capobianco²,

Careaga³

et al. 2014

Journal of Endocrinology

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Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B 4 (LTB 4 , PPARa ligand) or 15deoxyD 12,14 prostaglandin J 2 (15dPGJ 2 , PPARg ligand) and ii) fed during pregnancy with 6% olive oil-or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB 4 and partially restored by 15dPGJ 2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil-and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

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Leukotriene B4 Is a Physiologically Relevant Endogenous Peroxisome Proliferator-activated Receptor-α Agonist

Cited by 110 publications

References 27 publications

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

The Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Induced 5-Lipoxygenase-Leukotriene B4 Cascade Plays Key Roles in KSHV Latency, Monocyte Recruitment, and Lipogenesis

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats

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