Potential relationship between dietary long-chain saturated fatty acids and hypothalamic dysfunction in obesity

Domenico Sergi*, Lynda M Williams

*Corresponding author for this work

Research output: Contribution to journalArticle


Diet-induced hypothalamic inflammation, which leads to hypothalamic dysfunction and a loss of regulation of energy balance, is emerging as a potential driver of obesity. Excessive intake of long-chain saturated fatty acids is held to be the causative dietary component in hypothalamic inflammation. This review summarizes current evidence on the role of long-chain saturated fatty acids in promoting hypothalamic inflammation and the related induction of central insulin and leptin insensitivity. Particularly, the present review focuses on the molecular mechanisms linking long-chain saturated fatty acids and hypothalamic inflammation, emphasizing the metabolic fate of fatty acids and the resulting lipotoxicity, which is a key driver of hypothalamic dysfunction. In conclusion, long-chain saturated fatty acids are key nutrients that promote hypothalamic inflammation and dysfunction by fostering the build-up of lipotoxic lipid species, such as ceramide. Furthermore, when long-chain saturated fatty acids are consumed in combination with high levels of refined carbohydrates, the proinflammatory effects are exacerbated via a mechanism that relies on the formation of advanced glycation end products.

Original languageEnglish
Pages (from-to)261-277
Number of pages17
JournalNutrition Reviews
Issue number4
Early online date18 Sep 2019
Publication statusPublished - Apr 2020



  • advanced glycation end products
  • hypothalamic inflammation
  • lipotoxicity
  • long chain saturated fatty acids

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