TY - JOUR
T1 - Targeting the Liver-Brain Axis with Hop-Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice
AU - Paraiso, Ines L.
AU - Revel, Johana S.
AU - Choi, Jaewoo
AU - Miranda, Cristobal L.
AU - Lak, Parnian
AU - Kioussi, Chrissa
AU - Bobe, Gerd
AU - Gombart, Adrian F.
AU - Raber, Jacob
AU - Maier, Claudia S.
AU - Stevens, Jan F.
N1 - Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - bile acids
KW - ceramide
KW - cholesterol
KW - obesity
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U2 - 10.1002/mnfr.202000341
DO - 10.1002/mnfr.202000341
M3 - Article
C2 - 32627931
AN - SCOPUS:85087570214
SN - 1613-4125
VL - 64
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 15
M1 - 2000341
ER -