Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase
Abstract
The 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 pre-treated 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.
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This rise in lipid utilization improves insulin sensitivity in these cells and suppresses inflammatory signaling.
“In fact, this rise in lipid utilization improves insulin sensitivity in these cells and suppresses inflammatory signaling ([50](#B50)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [50]
Recent studies have shown beneficial effects of increased fatty acid oxidation and lipolysis in adipocytes, through direct CPT1A overexpression.
“Although the exact physiological role of FAO in WAT remains to be determined, recent studies have shown beneficial effects of increased FAO and lipolysis in adipocytes, through direct CPT1A overexpression.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [50]
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- Authors
- Gao, X., Li, K., Hui, X., Kong, X., Sweeney, G., Wang, Y., Xu, A., Teng, M., Liu, P., & Wu, D.
- Affiliations
- Chinese Academy of Sciences (CN)
- University of Science and Technology of China (CN)
- University of Hong Kong (HK)
- 458th Hospital PLA (CN)
- York University (CA)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Gao, Xuefei
- Li, Kuai
- Wu, Donghai
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2011-04-13
- Volume
- 435
- Issue
- 3
- Pages
- 723-732
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W1982342677
- Cited by
- 68
- References
- 32
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 2 · 2019: 7 · 2018: 1 · 2017: 8 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 4 · 2012: 7
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- CPT1A, adipocytes, c-Jun N-terminal kinase, JNK, fatty acid beta-oxidation, free fatty acids, fatty acid uptake, adipocyte inflammation, TNF-α, interleukin-6, adipokines, etomoxir, SP600125, insulin sensitivity
- MeSH terms
- Animals, Carnitine O-Palmitoyltransferase, Cell Differentiation, Epoxy Compounds, Fatty Acids, Humans, Gene Expression Regulation, Enzymologic, Adipocytes, 3T3-L1 Cells, JNK Mitogen-Activated Protein Kinases, Lipid Metabolism, Mice
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