| Autor: |
Eveline Gart, Kanita Salic, Martine C. Morrison, Martin Giera, Joline Attema, Christa de Ruiter, Martien Caspers, Frank Schuren, Ivana Bobeldijk-Pastorova, Marianne Heer, Yan Qin, Robert Kleemann |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Frontiers in Nutrition, Vol 9 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2296-861X |
| DOI: |
10.3389/fnut.2022.904740 |
| Popis: |
Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disorder that is associated with gut dysbiosis, enhanced gut permeability, adiposity and insulin resistance. Prebiotics such as human milk oligosaccharide 2′-fucosyllactose are thought to primarily improve gut health and it is uncertain whether they would affect more distant organs. This study investigates whether 2′-fucosyllactose can alleviate NAFLD development in manifest obesity. Obese hyperinsulinemic Ldlr-/-.Leiden mice, after an 8 week run-in on a high-fat diet (HFD), were treated with 2′-fucosyllactose by oral gavage until week 28 and compared to HFD-vehicle controls. 2′-fucosyllactose did not affect food intake, body weight, total fat mass or plasma lipids. 2′-fucosyllactose altered the fecal microbiota composition which was paralleled by a suppression of HFD-induced gut permeability at t = 12 weeks. 2′-fucosyllactose significantly attenuated the development of NAFLD by reducing microvesicular steatosis. These hepatoprotective effects were supported by upstream regulator analyses showing that 2′-fucosyllactose activated ACOX1 (involved in lipid catabolism), while deactivating SREBF1 (involved in lipogenesis). Furthermore, 2′-fucosyllactose suppressed ATF4, ATF6, ERN1, and NUPR1 all of which participate in endoplasmic reticulum stress. 2′-fucosyllactose reduced fasting insulin concentrations and HOMA-IR, which was corroborated by decreased intrahepatic diacylglycerols. In conclusion, long-term supplementation with 2′-fucosyllactose can counteract the detrimental effects of HFD on gut dysbiosis and gut permeability and attenuates the development of liver steatosis. The observed reduction in intrahepatic diacylglycerols provides a mechanistic rationale for the improvement of hyperinsulinemia and supports the use of 2′-fucosyllactose to correct dysmetabolism and insulin resistance. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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