FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2997062013> ?p ?o ?g. }

• W2997062013 endingPage "225" @default.
• W2997062013 startingPage "212" @default.
• W2997062013 abstract "Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor family, playing pivotal roles in regulating glucose and lipid metabolism as well as inflammation. While characterizing potential PPARγ ligand activity of natural compounds in macrophages, we investigated their influence on the expression of adipophilin [perilipin 2 (PLIN2)], a well-known PPARγ target. To confirm that a compound regulates PLIN2 expression via PPARγ, we performed experiments using the widely used PPARγ antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662). Surprisingly, instead of blocking upregulation of PLIN2 expression in THP-1 macrophages, expression was concentration-dependently induced by GW9662 at concentrations and under conditions commonly used. We found that this unexpected upregulation occurs in many human and murine macrophage cell models and also primary cells. Profiling expression of PPAR target genes showed upregulation of several genes involved in lipid uptake, transport, and storage as well as fatty acid synthesis by GW9662. In line with this and with upregulation of PLIN2 protein, GW9662 elevated lipogenesis and increased triglyceride levels. Finally, we identified PPARδ as a mediator of the substantial unexpected effects of GW9662. Our findings show that: 1) the PPARγ antagonist GW9662 unexpectedly activates PPARδ-mediated signaling in macrophages, 2) GW9662 significantly affects lipid metabolism in macrophages, 3) careful validation of experimental conditions and results is required for experiments involving GW9662, and 4) published studies in a context comparable to this work may have reported erroneous results if PPARγ independence was demonstrated using GW9662 only. In light of our findings, certain existing studies might require reinterpretation regarding the role of PPARγ SIGNIFICANCE STATEMENT: Peroxisome proliferator-activated receptors (PPARs) are targets for the treatment of various diseases, as they are key regulators of inflammation as well as lipid and glucose metabolism. Hence, reliable tools to characterize the molecular effects of PPARs are indispensable. We describe profound and unexpected off-target effects of the PPARγ antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662) involving PPARδ and in turn affecting macrophage lipid metabolism. Our results question certain existing studies using GW9662 and make better experimental design of future studies necessary." @default.
• W2997062013 created "2020-01-10" @default.
• W2997062013 creator A5001997993 @default.
• W2997062013 creator A5007071280 @default.
• W2997062013 creator A5016282627 @default.
• W2997062013 creator A5020124861 @default.
• W2997062013 creator A5021272462 @default.
• W2997062013 creator A5030411494 @default.
• W2997062013 creator A5036998308 @default.
• W2997062013 creator A5041140620 @default.
• W2997062013 creator A5063602616 @default.
• W2997062013 creator A5077615625 @default.
• W2997062013 creator A5090575036 @default.
• W2997062013 date "2019-12-23" @default.
• W2997062013 modified "2023-10-17" @default.
• W2997062013 title "The Peroxisome Proliferator–Activated Receptor (PPAR)-<i>γ</i>Antagonist 2-Chloro-5-Nitro-N-Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPAR<i>δ</i>and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages" @default.
• W2997062013 cites W1494611500 @default.
• W2997062013 cites W1510733531 @default.
• W2997062013 cites W1921122390 @default.
• W2997062013 cites W1967488096 @default.
• W2997062013 cites W1970669390 @default.
• W2997062013 cites W1971486720 @default.
• W2997062013 cites W1976621212 @default.
• W2997062013 cites W1978065594 @default.
• W2997062013 cites W1987146541 @default.
• W2997062013 cites W1995975692 @default.
• W2997062013 cites W2000251574 @default.
• W2997062013 cites W2003927905 @default.
• W2997062013 cites W2016918631 @default.
• W2997062013 cites W2021681950 @default.
• W2997062013 cites W2027030929 @default.
• W2997062013 cites W2028697010 @default.
• W2997062013 cites W2038259293 @default.
• W2997062013 cites W2038654926 @default.
• W2997062013 cites W2050910681 @default.
• W2997062013 cites W2052389900 @default.
• W2997062013 cites W2054066779 @default.
• W2997062013 cites W2058301937 @default.
• W2997062013 cites W2059222861 @default.
• W2997062013 cites W2060905615 @default.
• W2997062013 cites W2062429936 @default.
• W2997062013 cites W2063464658 @default.
• W2997062013 cites W2068207796 @default.
• W2997062013 cites W2076604793 @default.
• W2997062013 cites W2087788651 @default.
• W2997062013 cites W2089687829 @default.
• W2997062013 cites W2094597422 @default.
• W2997062013 cites W2097511872 @default.
• W2997062013 cites W2099939845 @default.
• W2997062013 cites W2101460040 @default.
• W2997062013 cites W2103618523 @default.
• W2997062013 cites W2105634159 @default.
• W2997062013 cites W2114597279 @default.
• W2997062013 cites W2121241298 @default.
• W2997062013 cites W2126218858 @default.
• W2997062013 cites W2128469803 @default.
• W2997062013 cites W2129205142 @default.
• W2997062013 cites W2147593845 @default.
• W2997062013 cites W2160521357 @default.
• W2997062013 cites W2167908723 @default.
• W2997062013 cites W2170647741 @default.
• W2997062013 cites W2170651298 @default.
• W2997062013 cites W2398302992 @default.
• W2997062013 cites W2807900389 @default.
• W2997062013 cites W2835900673 @default.
• W2997062013 cites W2883888207 @default.
• W2997062013 cites W2899394453 @default.
• W2997062013 cites W4244288643 @default.
• W2997062013 doi "https://doi.org/10.1124/mol.119.117887" @default.
• W2997062013 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31871304" @default.
• W2997062013 hasPublicationYear "2019" @default.
• W2997062013 type Work @default.
• W2997062013 sameAs 2997062013 @default.
• W2997062013 citedByCount "18" @default.
• W2997062013 countsByYear W29970620132021 @default.
• W2997062013 countsByYear W29970620132022 @default.
• W2997062013 countsByYear W29970620132023 @default.
• W2997062013 crossrefType "journal-article" @default.
• W2997062013 hasAuthorship W2997062013A5001997993 @default.
• W2997062013 hasAuthorship W2997062013A5007071280 @default.
• W2997062013 hasAuthorship W2997062013A5016282627 @default.
• W2997062013 hasAuthorship W2997062013A5020124861 @default.
• W2997062013 hasAuthorship W2997062013A5021272462 @default.
• W2997062013 hasAuthorship W2997062013A5030411494 @default.
• W2997062013 hasAuthorship W2997062013A5036998308 @default.
• W2997062013 hasAuthorship W2997062013A5041140620 @default.
• W2997062013 hasAuthorship W2997062013A5063602616 @default.
• W2997062013 hasAuthorship W2997062013A5077615625 @default.
• W2997062013 hasAuthorship W2997062013A5090575036 @default.
• W2997062013 hasBestOaLocation W29970620131 @default.
• W2997062013 hasConcept C104317684 @default.
• W2997062013 hasConcept C126322002 @default.
• W2997062013 hasConcept C127078168 @default.
• W2997062013 hasConcept C127561419 @default.
• W2997062013 hasConcept C134018914 @default.
• W2997062013 hasConcept C140985366 @default.
• W2997062013 hasConcept C141359234 @default.
• W2997062013 hasConcept C170493617 @default.

• next