Targeting the Liver-Brain Axis with Hop-Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice

Ines L. Paraiso, Johana S. Revel, Jaewoo Choi, Cristobal L. Miranda, Parnian Lak, Chrissa Kioussi, Gerd Bobe, Adrian F. Gombart, Jacob Raber, Claudia S. Maier, Jan F. Stevens

Research output: Contribution to journalArticle

Abstract

Scope: Sphingolipids including ceramides are implicated in the pathogenesis of obesity and insulin resistance. Correspondingly, inhibition of pro-inflammatory and neurotoxic ceramide accumulation prevents obesity-mediated insulin resistance and cognitive impairment. Increasing evidence suggests the farnesoid X receptor (FXR) is involved in ceramide metabolism, as bile acid-FXR crosstalk controls ceramide levels along the gut-liver axis. The authors previously reported that FXR agonist xanthohumol (XN), the principal prenylated flavonoid in hops (Humulus lupulus), and its hydrogenated derivatives, α,β-dihydroxanthohumol (DXN), and tetrahydroxanthohumol (TXN), ameliorated obesity-mediated insulin resistance, and cognitive impairment in mice fed a high-fat diet. Methods and results: To better understand how the flavonoids improve both, lipid and bile acid profiles in the liver are analyzed, sphingolipid relative abundance in the hippocampus is measured, and linked them to metabolic and neurocognitive performance. XN, DXN, and TXN (30 mg kg−1 BW per day) decrease ceramide content in liver and hippocampus; the latter is linked to improvements in spatial learning and memory. In addition, XN, DXN, and TXN decrease hepatic cholesterol content by enhancing de novo synthesis of bile acids. Conclusion: These observations suggest that XN, DXN, and TXN may alleviate obesity-induced metabolic and neurocognitive impairments by targeting the liver-brain axis.

Original languageEnglish (US)
Article number2000341
JournalMolecular Nutrition and Food Research
Volume64
Issue number15
DOIs
StatePublished - Aug 1 2020

Keywords

  • bile acids
  • ceramide
  • cholesterol
  • obesity

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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    Paraiso, I. L., Revel, J. S., Choi, J., Miranda, C. L., Lak, P., Kioussi, C., Bobe, G., Gombart, A. F., Raber, J., Maier, C. S., & Stevens, J. F. (2020). Targeting the Liver-Brain Axis with Hop-Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice. Molecular Nutrition and Food Research, 64(15), [2000341]. https://doi.org/10.1002/mnfr.202000341