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Article: Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase
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TitleCarnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase
 
AuthorsGao, X5
Li, K5 3
Hui, X2
Kong, X6
Sweeney, G1
Wang, Y2
Xu, A2
Teng, M3
Liu, P4
Wu, D5
 
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
 
CitationBiochemical Journal, 2011, v. 435 n. 3, p. 723-732 [How to Cite?]
DOI: http://dx.doi.org/10.1042/BJ20101680
 
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.
 
ISSN0264-6021
2012 Impact Factor: 4.654
2012 SCImago Journal Rankings: 2.494
 
DOIhttp://dx.doi.org/10.1042/BJ20101680
 
ISI Accession Number IDWOS:000290742000019
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].

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorGao, X
 
dc.contributor.authorLi, K
 
dc.contributor.authorHui, X
 
dc.contributor.authorKong, X
 
dc.contributor.authorSweeney, G
 
dc.contributor.authorWang, Y
 
dc.contributor.authorXu, A
 
dc.contributor.authorTeng, M
 
dc.contributor.authorLiu, P
 
dc.contributor.authorWu, D
 
dc.date.accessioned2011-09-23T05:50:08Z
 
dc.date.available2011-09-23T05:50:08Z
 
dc.date.issued2011
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationBiochemical Journal, 2011, v. 435 n. 3, p. 723-732 [How to Cite?]
DOI: http://dx.doi.org/10.1042/BJ20101680
 
dc.identifier.citeulike9286491
 
dc.identifier.doihttp://dx.doi.org/10.1042/BJ20101680
 
dc.identifier.eissn1470-8728
 
dc.identifier.epage732
 
dc.identifier.hkuros194037
 
dc.identifier.isiWOS:000290742000019
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].

 
dc.identifier.issn0264-6021
2012 Impact Factor: 4.654
2012 SCImago Journal Rankings: 2.494
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmid21348853
 
dc.identifier.scopuseid_2-s2.0-79954480208
 
dc.identifier.spage723
 
dc.identifier.urihttp://hdl.handle.net/10722/139451
 
dc.identifier.volume435
 
dc.languageeng
 
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.org
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBiochemical Journal
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThe final version of record is available at [http://www.biochemj.org/bj/default.htm].
 
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.subjectAdipocyte
 
dc.subjectc-Jun N-terminal kinase (JNK)
 
dc.subjectCarnitine palmitoyltransferase 1A (CPT1A)
 
dc.subjectFatty acid
 
dc.subjectInsulin resistance
 
dc.subjectPro-inflammatory adipokine
 
dc.titleCarnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase
 
dc.typeArticle
 
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Author Affiliations
  1. York University
  2. The University of Hong Kong
  3. University of Science and Technology of China
  4. Wellcome Trust Sanger Institute
  5. Chinese Academy of Sciences
  6. 458th Hospital of PLA