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High-fat diet intake ameliorates the expression of hedgehog signaling pathway in adult rat liver

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Abstract

Background

Disproportionate fatty diet intake provokes hepatic lipid accumulation that causes non-alcoholic fatty liver disease, triggering the embryonically conserved Hedgehog (Hh) pathway in the adult liver. The present study incorporates exploring the impact of chronically administered unsaturated (D-1) and saturated (D-2) fat-enriched diets on hematological parameters, liver functioning, and lipid profile in the rat model. Besides, hepatohistology and real time gene expression analysis of Hh signaling pathway genes i.e., Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were carried out.

Methods and results

Fifteen Rattus norvegicus (♂) of 200 ± 25 g weight were grouped into control, D-1, and D-2. Animals were fed on their respective diets for 16 weeks. Fatty diet intake resulted in neutropenia, lymphocytosis, monocytosis, polycythemia, and macrocytosis in both experimental groups. Altered liver injury biomarkers, hypertriglyceridemia, and significantly increased very-low-density lipoprotein VLDL were also noted in both high-fat diet (HFD) groups as compared to control. Hepatohistological examination showed disrupted microarchitecture, infiltration of inflammatory cells, cellular necrosis, widened sinusoidal spaces, and microvesicular steatotic hepatocytes in D-1 and D-2. Collagen deposition in both HFD groups marks the extent of fibrosis. Significant upregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, Shh Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated in D-1. In D-2 Shh, Hhip, and Smo expressions were upregulated, Ihh exhibited downregulation as compared to control.

Conclusion

Excess fat deposits in liver due to chronic consumption of high-fat diet results in anomalous architecture and functioning.

Graphical abstract

High-fat diet induced significant variations in Hh pathway genes expression; especially Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated. Infiltration of inflammatory cells (), widened sinusoidal spaces (▲), cellular necrosis, and micro vesicular steatotic hepatocytes (*) were shown in the liver. Significant collagen deposition in both HFD groups i.e. D-1 and D-2 confirmed liver fibrosis. Excessive intake of dietary fats impaired normal liver functioning and liver inflammation triggered Hh signaling in adult rats.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors are thankful to the Vice-chancellor of the University of the Punjab, Lahore, Pakistan, for providing support for the accomplishment of this study.

Funding

The authors are thankful to the Vice-chancellor of the University of the Punjab, Lahore, Pakistan, for providing support for the accomplishment of this study.

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Authors and Affiliations

  1. Institute of Zoology, University of the Punjab, Q-A- Campus, Lahore, 54590, Pakistan

    Rabia Mehmood, Nadeem Sheikh, Muddasir Hassan Abbasi & Maryam Mukhtar

  2. Department of Zoology, Faculty of Sciences, University of Central Punjab, Lahore, Pakistan

    Muhammad Babar Khawar

  3. Department of Zoology, University of Okara, Okara, Punjab, Pakistan

    Muddasir Hassan Abbasi

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  1. Rabia Mehmood
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Contributions

RM performed the major experiments, did the statistical analysis, and wrote the initial draft and interpretation. MBK and MHA interpreted the findings, provided technical assistance, wrote and approved the final draft of the manuscript. MM performed part of the experiments. NS conceived the idea, acquired funds, approved the final draft, and supervised the whole project.

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Correspondence to Nadeem Sheikh.

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The study was conducted in agreement with the institutional guidelines approved by the Local Ethical and Review Committee of the Department of Zoology, University of the Punjab, Lahore, Pakistan (Ref.D/621/U.Z).

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Mehmood, R., Sheikh, N., Khawar, M.B. et al. High-fat diet intake ameliorates the expression of hedgehog signaling pathway in adult rat liver. Mol Biol Rep 49, 1985–1994 (2022). https://doi.org/10.1007/s11033-021-07012-6

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  • DOI: https://doi.org/10.1007/s11033-021-07012-6

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