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High-fat diet with alcohol elevate oxidative stress which cause hyperlipidemia by inducing mutation in the ANGPTL3 locus

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International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Background

Angiopoietin-like 3 (ANGPTL3) is a secreted protein which predominantly expressed in the liver, and involves in upregulation of lipid metabolism. Mutation in ANGPTL3 leads to decrease in the concentration of triglycerides (TGs), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which makes it a promising candidate for hyperlipidemia.

Objectives

The present study aims to identify the effect of alcohol and high-fat diet, on the ANGPTL3 locus, in the development of hyperlipidemia.

Methods

24 male Wister rats divided into four groups viz. control group (regular diet), HFD group (high-fat diet), ALC group (alcohol consuming), and HFD + ALC group (high-fat diet + alcohol consuming). All the groups were followed up for 12 weeks. Malondialdehyde (MDA), total body weight, TG, LDL, and HDL level were measured at the endpoint of study, and gene mutation analysis was also done for ANGPTL3.

Results

MDA level found to be significantly increases in HFD + ALC group, HFD group, and ALC group compared to the control group. RFLP analysis revealed a mutation in the ANGPTL3 gene which occurred only in HFD + ALC group. Moreover, body weight, TG, LDL, and HDL found to increase significantly in HFD + ALC, HFD, and ALC group as compared to the control group.

Conclusions

The present finding indicates is that high-fat diet with alcohol increases the oxidative stress in the liver, which causes a gain of function mutation in ANGPTL3 gene, resulting in hyperlipidemia.

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Acknowledgements

The present work was conducted at the Department of Biotechnology and Guwahati Medical College & Hospital, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam (26.1599° N, 91.7679° E). The authors highly acknowledge all the colleagues who reviewed the present work.

Funding

The present work is funded by the department’s internal funds provided by NIPER to Jyoti Saini and Junior Research Fellowship (JRF) provided by ICMR, New Delhi, wide file no. 3/13/JRF-2015/HRD to Atul K Goyal.

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Contributions

Jyoti Saini and Ashok K Jangra designed the concept, conducted the study, and generated the raw data. Atul K Goyal compiled the raw data, did statistical analysis, and drafted the manuscript.

Corresponding author

Correspondence to Atul Kumar Goyal.

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The authors declare that they have no conflict of interest.

Ethical statement

The study was approved by the Institutional Animal Ethics Committee (IAEC), Guwahati Medical College & Hospital (CPSCEA Registration No. 351;3/1/2001) under Approval No. MC/32/2013/36.

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Saini, J., Goyal, A.K. & Jangra, A. High-fat diet with alcohol elevate oxidative stress which cause hyperlipidemia by inducing mutation in the ANGPTL3 locus. Int J Diabetes Dev Ctries 40, 269–275 (2020). https://doi.org/10.1007/s13410-019-00773-8

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