Targeting the Liver‐Brain Axis with Hop‐Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice. Issue 15 (6th July 2020)

• Record Type: Journal Article
• Authors: Paraiso, Ines L.; Revel, Johana S.; Choi, Jaewoo; Miranda, Cristobal L.; Lak, Parnian; Kioussi, Chrissa; Bobe, Gerd; Gombart, Adrian F.; Raber, Jacob; Maier, Claudia S.; Stevens, Jan F.
• Is Part Of: Molecular nutrition & food research. Volume 64:Issue 15(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-07-06
• Subjects: bile acids -- ceramide -- cholesterol -- obesity; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202000341
• Languages: English
• ISSNs: 1613-4125

Abstract

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. Abstract : Xanthohumol (XN), a flavonoid from hops (Humulus lupulus), and its hydrogenated derivatives, α, β‐dihydroxanthohumol (DXN) and tetrahydroxanthohumol (TXN) decrease hepatic cholesterol by enhancing de novo synthesis of bile acids and decrease ceramide content in liver and hippocampus. The subsequent amelioration of obesity‐induced metabolic and neurocognitive impairments suggests that XN, DXN, and TXN may mitigate metabolic syndrome by targeting the liver‐brain axis.