Gut-liver axis modulation in fructose-fed mice: a role for PPAR-alpha and linagliptin

in Journal of Endocrinology
Authors:
Flávia Maria Silva-Veiga Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Carolline Santos Miranda Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Fabiane Ferreira Martins Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Julio Beltrame Daleprane Laboratory for Studies of Interactions between Nutrition and Genetics, LEING, Institute of Nutrition, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Carlos Alberto Mandarim-de-Lacerda Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Vanessa Souza-Mello Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Correspondence should be addressed to V Souza-Mello: souzamello.uerj@gmail.com
DOI:
https://doi.org/10.1530/JOE-20-0139
Volume/Issue:
Volume 247: Issue 1
Article Type:
Research Article
Page Range:
11–24
Online Publication Date:
Oct 2020
Copyright:
© 2020 Society for Endocrinology 2020
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Fructose dietary intake affects the composition of the intestinal microbiota and influences the development of hepatic steatosis. Endotoxins produced by gram-negative bacteria alter intestinal permeability and cause bacterial translocation. This study evaluated the effects of gut microbiota modulation by a purified PPAR-alpha agonist (WY14643), a DPP-4 inhibitor (linagliptin), or their association on intestinal barrier integrity, endotoxemia, and hepatic energy metabolism in high-fructose-fed C57BL/6 mice. Fifty mice were divided to receive the control diet (C group) or the high-fructose diet (HFRU) for 12 weeks. Subsequently, the HFRU group was divided to initiate the treatment with PPAR-alpha agonist (3.5 mg/kg/BM) and DPP-4 inhibitor (15 mg/kg/BM). The HFRU group had glucose intolerance, endotoxemia, and dysbiosis (with increased Proteobacteria) without changes in body mass in comparison with the C group. HFRU group showed damaged intestinal ultrastructure, which led to liver inflammation and marked hepatic steatosis in the HFRU group when compared to the C group. PPAR-alpha activation and DPP-4 inhibition countered glucose intolerance, endotoxemia, and dysbiosis, ameliorating the ultrastructure of the intestinal barrier and reducing Tlr4 expression in the liver of treated animals. These beneficial effects suppressed lipogenesis and mitigated hepatic steatosis. In conclusion, the results herein propose a role for PPAR-alpha activation, DPP-4 inhibition, and their association in attenuating hepatic steatosis by gut-liver axis modulation in high-fructose mice model. These observations suggest these treatments as potential targets to treat hepatic steatosis and avoid its progression.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
14
Article Type:
Research Article
Received Date:
03 Jul 2020
Accepted Date:
13 Jul 2020
Print Publication Date:
01 Oct 2020
Online Publication Date:
Oct 2020
Keywords:
fructose; hepatic steatosis; gut microbiota; PPAR-alpha; DPP-4 inhibition

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