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Article: Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase

TitleCarnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase
Authors
KeywordsAdipocyte
c-Jun N-terminal kinase (JNK)
Carnitine palmitoyltransferase 1A (CPT1A)
Fatty acid
Insulin resistance
Pro-inflammatory adipokine
Issue Date2011
PublisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.org
Citation
Biochemical Journal, 2011, v. 435 n. 3, p. 723-732 How to Cite?
AbstractThe adipocyte is the principal cell type for fat storage. CPT1 (carnitine palmitoyltransferase-1) is the rate-limiting enzyme for fatty acid β-oxidation, but the physiological role of CPT1 in adipocytes remains unclear. In the present study,we focused on the specific role of CPT1A in the normal functioning of adipocytes. Three 3T3-L1 adipocyte cell lines stably expressing hCPT1A (human CPT1A) cDNA, mouse CPT1A shRNA (short-hairpin RNA) or GFP (green fluorescent protein) were generated and the biological functions of these cell lines were characterized. Alteration in CPT1 activity, either by ectopic overexpression or pharmacological inhibition using etomoxir, did not affect adipocyte differentiation. However, overexpression of hCPT1A significantly reduced the content of intracellular NEFAs (non-esterified fatty acids) compared with the control cells when adipocytes were challenged with fatty acids. The changes were accompanied by an increase in fatty acid uptake and a decrease in fatty acid release. Interestingly, CPT1A protected against fatty acid-induced insulin resistance and expression of pro-inflammatory adipokines such as TNF-α (tumour necrosis factor-α) and IL-6 (interleukin-6) in adipocytes. Further studies demonstrated that JNK (c-Jun N terminal kinase) activity was substantially suppressed upon CPT1A overexpression, whereas knockdown or pharmacological inhibition of CPT1 caused a significant enhancement of JNK activity. The specific inhibitor of JNK SP600125 largely abolished the changes caused by the shRNA- and etomoxir-mediated decrease in CPT1 activity. Moreover, C2C12 myocytes co-cultured with adipocytes pretreated with fatty acids displayed altered insulin sensitivity. Taken together, our findings have identified a favourable role for CPT1A in adipocytes to attenuate fatty acid-evoked insulin resistance and inflammation via suppression of JNK. © The Authors Journal compilation © 2011 Biochemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/139451
ISSN
2015 Impact Factor: 3.562
2015 SCImago Journal Rankings: 2.582
ISI Accession Number ID
Funding AgencyGrant Number
National Basic Research Program of China (973 Program)2011CB504004
2010CB945500
National Natural Science Foundation of China31000353
30970637
Chinese Academy of Sciences
Guangzhou Administration of Science and Technology2007Z2-E4021
Funding Information:

This work was supported, in part, by the National Basic Research Program of China (973 Program) [grant numbers 2011CB504004, 2010CB945500], the National Natural Science Foundation of China [grant numbers 31000353, 30970637], and the Knowledge Innovation Program of the Chinese Academy of Sciences and Guangzhou Administration of Science and Technology [grant number 2007Z2-E4021].

References

 

DC FieldValueLanguage
dc.contributor.authorGao, Xen_HK
dc.contributor.authorLi, Ken_HK
dc.contributor.authorHui, Xen_HK
dc.contributor.authorKong, Xen_HK
dc.contributor.authorSweeney, Gen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorTeng, Men_HK
dc.contributor.authorLiu, Pen_HK
dc.contributor.authorWu, Den_HK
dc.date.accessioned2011-09-23T05:50:08Z-
dc.date.available2011-09-23T05:50:08Z-
dc.date.issued2011en_HK
dc.identifier.citationBiochemical Journal, 2011, v. 435 n. 3, p. 723-732en_HK
dc.identifier.issn0264-6021en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139451-
dc.description.abstractThe adipocyte is the principal cell type for fat storage. CPT1 (carnitine palmitoyltransferase-1) is the rate-limiting enzyme for fatty acid β-oxidation, but the physiological role of CPT1 in adipocytes remains unclear. In the present study,we focused on the specific role of CPT1A in the normal functioning of adipocytes. Three 3T3-L1 adipocyte cell lines stably expressing hCPT1A (human CPT1A) cDNA, mouse CPT1A shRNA (short-hairpin RNA) or GFP (green fluorescent protein) were generated and the biological functions of these cell lines were characterized. Alteration in CPT1 activity, either by ectopic overexpression or pharmacological inhibition using etomoxir, did not affect adipocyte differentiation. However, overexpression of hCPT1A significantly reduced the content of intracellular NEFAs (non-esterified fatty acids) compared with the control cells when adipocytes were challenged with fatty acids. The changes were accompanied by an increase in fatty acid uptake and a decrease in fatty acid release. Interestingly, CPT1A protected against fatty acid-induced insulin resistance and expression of pro-inflammatory adipokines such as TNF-α (tumour necrosis factor-α) and IL-6 (interleukin-6) in adipocytes. Further studies demonstrated that JNK (c-Jun N terminal kinase) activity was substantially suppressed upon CPT1A overexpression, whereas knockdown or pharmacological inhibition of CPT1 caused a significant enhancement of JNK activity. The specific inhibitor of JNK SP600125 largely abolished the changes caused by the shRNA- and etomoxir-mediated decrease in CPT1 activity. Moreover, C2C12 myocytes co-cultured with adipocytes pretreated with fatty acids displayed altered insulin sensitivity. Taken together, our findings have identified a favourable role for CPT1A in adipocytes to attenuate fatty acid-evoked insulin resistance and inflammation via suppression of JNK. © The Authors Journal compilation © 2011 Biochemical Society.en_HK
dc.languageengen_US
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.orgen_HK
dc.relation.ispartofBiochemical Journalen_HK
dc.rightsThe final version of record is available at [http://www.biochemj.org/bj/default.htm].-
dc.subjectAdipocyteen_HK
dc.subjectc-Jun N-terminal kinase (JNK)en_HK
dc.subjectCarnitine palmitoyltransferase 1A (CPT1A)en_HK
dc.subjectFatty aciden_HK
dc.subjectInsulin resistanceen_HK
dc.subjectPro-inflammatory adipokineen_HK
dc.subject.mesh3T3-L1 Cells-
dc.subject.meshAdipocytes - drug effects - physiology-
dc.subject.meshCarnitine O-Palmitoyltransferase - antagonists and inhibitors - genetics - metabolism-
dc.subject.meshFatty Acids - toxicity-
dc.subject.meshJNK Mitogen-Activated Protein Kinases - genetics - metabolism-
dc.titleCarnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1470-8728 (Electronic) 0264-6021 (Linkin&volume=435&issue=3&spage=723&epage=32&date=2011&atitle=Carnitine+palmitoyltransferase+1A+prevents+fatty+acid-induced+adipocyte+dysfunction+through+suppression+of+c-Jun+N-terminal+kinaseen_US
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1042/BJ20101680en_HK
dc.identifier.pmid21348853-
dc.identifier.scopuseid_2-s2.0-79954480208en_HK
dc.identifier.hkuros194037en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79954480208&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume435en_HK
dc.identifier.issue3en_HK
dc.identifier.spage723en_HK
dc.identifier.epage732en_HK
dc.identifier.eissn1470-8728-
dc.identifier.isiWOS:000290742000019-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridGao, X=26028577700en_HK
dc.identifier.scopusauthoridLi, K=35205480100en_HK
dc.identifier.scopusauthoridHui, X=26666795900en_HK
dc.identifier.scopusauthoridKong, X=7202794607en_HK
dc.identifier.scopusauthoridSweeney, G=7102852659en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridTeng, M=7101891754en_HK
dc.identifier.scopusauthoridLiu, P=7404618110en_HK
dc.identifier.scopusauthoridWu, D=7404297751en_HK
dc.identifier.citeulike9286491-

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