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  • Pigment epithelium-derived factor (PEDF) suppresses IL-1β-mediated c-Jun N-terminal kinase (JNK) activation to improve hepatocyte insulin signaling.

Pigment epithelium-derived factor (PEDF) suppresses IL-1β-mediated c-Jun N-terminal kinase (JNK) activation to improve hepatocyte insulin signaling.

Endocrinology (2014-01-25)
Arijeet K Gattu, Andreas L Birkenfeld, Yasuko Iwakiri, Steven Jay, Mark Saltzman, Jennifer Doll, Petr Protiva, Varman T Samuel, Susan E Crawford, Chuhan Chung
ABSTRACT

Pigment epithelium-derived factor (PEDF) is an antiinflammatory protein that circulates at high levels in the metabolic syndrome. Metabolic studies of PEDF knockout (KO) mice were conducted to investigate the relationship between PEDF, inflammatory markers, and metabolic homeostasis. Male PEDF KO mice demonstrated a phenotype consisting of increased adiposity, glucose intolerance, and elevated serum levels of metabolites associated with the metabolic syndrome. Genome expression analysis revealed an increase in IL-1β signaling in the livers of PEDF KO mice that was accompanied by impaired IRS and Akt signaling. In human hepatocytes, PEDF blocked the effects of an IL-1β challenge by suppressing activation of the inflammatory mediator c-Jun N-terminal kinase while restoring Akt signaling. RNA interference of PEDF in human hepatocytes was permissive for c-Jun N-terminal kinase activation and decreased Akt signaling. A metabolomics profile identified elevated circulating levels of tricarboxyclic acid cycle intermediates including succinate, an inducer of IL-1β, in PEDF KO mice. Succinate-dependent IL-1β expression was blocked by PEDF in PEDF KO, but not wild-type hepatocytes. In vivo, PEDF restoration reduced hyperglycemia and improved hepatic insulin signaling in PEDF KO mice. These findings identify elevated PEDF as a homeostatic mechanism in the human metabolic syndrome.

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Palmitic acid, ≥98%, FCC, FG
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Palmitic acid, Pharmaceutical Secondary Standard; Certified Reference Material
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Palmitic acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
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Palmitic acid, BioXtra, ≥99%
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Palmitic acid, ≥99%
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Palmitic acid, analytical standard
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Palmitic acid, ≥98% palmitic acid basis (GC)
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Palmitic acid, natural, 98%, FG
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Palmitic acid, United States Pharmacopeia (USP) Reference Standard
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Palmitic acid, European Pharmacopoeia (EP) Reference Standard
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Succinic acid, ReagentPlus®, BioRenewable, ≥99.0%
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Succinic acid, BioXtra, BioRenewable, ≥99.0%
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Succinic acid, BioReagent, BioRenewable, suitable for cell culture, suitable for insect cell culture
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Succinic acid, purum p.a., ≥99.0% (T)
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Succinic acid, ACS reagent, ≥99.0%
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Succinic acid, SAJ special grade, ≥99.5%
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Succinic acid, puriss. p.a., ACS reagent, ≥99.5% (T)
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Succinic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
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Succinic acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
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