Palmitate Activates the NF-κB Transcription Factor and Induces IL-6 and TNFα Expression in 3T3-L1 Adipocytes

Ajuwon, Kolapo M.; Spurlock, Michel E.

doi:10.1093/jn/135.8.1841

Cited by 343Adipokines, Inflammation, and Metabolic DiseasesFatty Acid Research and HealthNF-κB Signaling Pathways

Palmitate Activates the NF-κB Transcription Factor and Induces IL-6 and TNFα Expression in 3T3-L1 Adipocytes

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Ajuwon, Kolapo M., Spurlock, Michel E.·2005·The Journal of Nutrition

DOI 10.1093/jn/135.8.1841

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Abstract

Fatty acids and their metabolites regulate gene expression and immunological pathways. Furthermore, obese individuals frequently have increased circulating fatty acid concentrations, and localized inflammation in adipose tissue may facilitate the systemic inflammation associated with the insulin resistance of obesity. Although palmitate induces inflammation (i.e., activates proinflammatory pathways) in myotubes, the effects of fatty acids on inflammatory processes in adipocytes have not been established. Therefore, we examined the potential for palmitate, laurate, and docosahexaenoic acid (DHA) to modulate inflammation in 3T3-L1 adipocytes. Palmitate, but not DHA or laurate, induced nuclear factor kappaB (NF-kappaB)-driven luciferase activity and interleukin-6 (IL-6) expression (P < 0.05). Inhibition of fatty acyl Co-A synthase (FACS) with triacsin C suppressed palmitate-induced NF-kappaB activation (P < 0.05), but caused an additive increase in palmitate-induced IL-6 expression (P < 0.05). Disrupting mitogen-activated protein kinase/Erk kinase (MEK) and protein kinase C (PKC) activity with U0126 and Bisindolylmaleimide (Bis), respectively, suppressed palmitate-induced IL-6 expression (P < 0.05), but had no effect on NF-kappaB reporter gene activity (P > 0.05). However, the phosphoinositide-3 kinase (PI3K) inhibitor, wortmannin, alone and additively with palmitate, activated the NF-kappaB reporter gene and induced IL-6 expression (P < 0.05). Palmitate also induced the mRNA expression of tumor necrosis factor alpha (TNFalpha) (P < 0.05), but the increase in mRNA abundance was not reflected in a greater protein concentration in the media (P > 0.05). These data indicate that palmitate induces inflammation in adipocytes, and that this is not a generalized effect of all SFA. Furthermore, PI3K may act constitutively to suppress inflammation. Consequently, inhibition of this enzyme may promote and exacerbate the inflammation in adipose tissue that is associated with obesity and insulin resistance.

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Authors: Ajuwon, K. M., & Spurlock, M. E.
Affiliations: Purdue University West Lafayette (US)
Corresponding author: Spurlock, Michel E.
ORCID: Ajuwon, Kolapo M.
Venue: The Journal of Nutrition
Publisher: Elsevier BV
Published: 2005-08
Volume: 135
Issue: 8
Pages: 1841-1846
ISSN: 0022-3166 (ISSN-L)
DOI: 10.1093/jn/135.8.1841
OpenAlex: W1938589063
Cited by: 343
References: 35
Citations by year: 2026: 2 · 2025: 5 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 17 · 2020: 15 · 2019: 23 · 2018: 16 · 2017: 15 · 2016: 22 · 2015: 26 · 2014: 28 · 2013: 21 · 2012: 13
FWCI: 11.95
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6392 d)
Locations: Journal of Nutrition (publishedVersion)
PubMed (publishedVersion)
Funders: Purdue University
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: palmitate, NF-κB activation, adipocyte inflammation, 3T3-L1 adipocytes, interleukin-6, TNF-α, saturated fatty acids, laurate, docosahexaenoic acid, triacsin C, protein kinase C, phosphatidylinositol 3-kinase, wortmannin, obesity, insulin resistance, adipose tissue inflammation
MeSH terms: Animals, Base Sequence, Docosahexaenoic Acids, Gene Expression Regulation, Luciferases, Tumor Necrosis Factor-alpha, Interleukin-6, Polymerase Chain Reaction, NF-kappa B, 3T3 Cells, Adipocytes, Genes, Reporter, DNA Primers, Palmitic Acid, Phosphatidylinositol 3-Kinases, Mice

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Palmitate Activates the NF-κB Transcription Factor and Induces IL-6 and TNFα Expression in 3T3-L1 Adipocytes

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