Abstract
A high-fat diet induces hypothalamic inflammation in rodents which, in turn, contributes to the development of obesity by eliciting both insulin and leptin resistance. However, the mechanism by which long-chain saturated fatty acids trigger inflammation is still contentious. To elucidate this mechanism, the effect of fatty acids on the expression of the pro-inflammatory cytokines IL-6 and TNFα was investigated in the mHypoE-N42 hypothalamic cell line (N42). N42 cells were treated with lauric acid (LA) and palmitic acid (PA). PA challenge was carried out in the presence of either a TLR4 inhibitor, a ceramide synthesis inhibitor (L-cycloserine), oleic acid (OA) or eicosapentaenoic acid (EPA). Intracellular ceramide accumulation was quantified using LC-ESI-MS/MS. PA but not LA upregulated IL-6 and TNFα. L-cycloserine, OA and EPA all counteracted PA-induced intracellular ceramide accumulation leading to a downregulation of IL-6 and TNFα. However, a TLR4 inhibitor failed to inhibit PA-induced upregulation of pro-inflammatory cytokines. In conclusion, PA induced the expression of IL-6 and TNFα in N42 neuronal cells independently of TLR4 but, partially, via ceramide synthesis with OA and EPA being anti-inflammatory by decreasing PA-induced intracellular ceramide build-up. Thus, ceramide accumulation represents one on the mechanisms by which PA induces inflammation in neurons.
Original language | English |
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Pages (from-to) | 321-334 |
Number of pages | 14 |
Journal | Nutritional Neuroscience |
Volume | 23 |
Issue number | 4 |
Early online date | 21 Jul 2018 |
DOIs | |
Publication status | Published - Apr 2020 |
Bibliographical note
Funding This work was supported by Scottish Universities Life Sciences Alliance (SULSA-MSD) studentship, the University of Aberdeen and the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS).Keywords
- Journal Article
- hypothalamic inflammation
- fatty acids
- hypothalamic neurons
- ceramide
- toll-like receptor 4
- Toll-like receptor 4
- ENDOPLASMIC-RETICULUM STRESS
- SATURATED FATTY-ACIDS
- Fatty acids
- BETA/NF-KAPPA-B
- LIPID-ACCUMULATION
- OBESITY
- INHIBITION
- INSULIN-RESISTANCE
- Ceramide
- GENE-EXPRESSION
- Hypothalamic inflammation
- CARNITINE PALMITOYLTRANSFERASE
- Hypothalamic neurons
- ADIPOSE-TISSUE