Palmitic acid triggers inflammatory responses in N42 cultured hypothalamic cells partially via ceramide synthesis but not via TLR4. (2nd April 2020)

• Record Type: Journal Article
• Authors: Sergi, Domenico; Morris, Amanda C.; Kahn, Darcy E.; McLean, Fiona H.; Hay, Elizabeth A.; Kubitz, Phil; MacKenzie, Alasdair; Martinoli, Maria G.; Drew, Janice E.; Williams, Lynda M.
• Is Part Of: Nutritional neuroscience. Volume 23:Number 4(2020)
• Page Start: 321
• Page End: 334
• Publication Date: 2020-04-02
• Subjects: Hypothalamic inflammation -- Fatty acids -- Hypothalamic neurons -- Ceramide -- Toll-like receptor 4; Neuropharmacology -- Periodicals; Diet -- Periodicals; Diet therapy -- Periodicals; Nutrition -- Periodicals; 615.78
• DOI: 10.1080/1028415X.2018.1501533
• Languages: English
• ISSNs: 1028-415X

Abstract

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.