Investigating dual inhibition of ACC and CD36 for the treatment of nonalcoholic fatty liver disease in mice

CJ Devereux; J Bayliss; SN Keenan; MK Montgomery; MJ Watt

Journal article

Investigating dual inhibition of ACC and CD36 for the treatment of nonalcoholic fatty liver disease in mice

CJ Devereux, J Bayliss, SN Keenan, MK Montgomery, MJ Watt

American Journal of Physiology Endocrinology and Metabolism | AMER PHYSIOLOGICAL SOC | Published : 2023

DOI: 10.1152/ajpendo.00161.2022

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Dysregulation in hepatic lipid metabolism, including increased fatty acid uptake and de novo lipogenesis (DNL), is a hallmark of NAFLD. Here, we investigated dual inhibition of the fatty acid transporter fatty acid translocase (FAT/CD36), and acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in DNL, for the treatment of NAFLD in mice. Mice with hepatic CD36 deletion (Cd36LKO) and wild-type littermates were fed a high-fat diet for 12 wk and treated daily with either oral administration of an ACC inhibitor (GS-834356, Gilead Sciences; ACCi) or vehicle for 8 wk. Neither CD36 deletion or ACC inhibit..

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University of Melbourne Researchers

Jacqueline Bayliss Author

Stacey Keenan Author

Magda Montgomery Author

Matt Watt Author

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Grants

Awarded by National Health and Medical Research Foundation of Australia (NHMRC)

Awarded by Diabetes Australia Research Trust

Awarded by NHMRC

Funding Acknowledgements

This work was supported by infrastructure and technical assistance from the Melbourne Mouse Metabolic Phenotyping Platform (MMMPP) and the Melbourne Histology Platform at the University of Melbourne. These studies were supported by funding from the National Health and Medical Research Foundation of Australia (NHMRC, APP1098972; APP1156508) and the Diabetes Australia Research Trust (Y20G-WATM) . C.J.D. was supported by the Australian Government Research Training Program Scholarship provided by the Australian Commonwealth Government and the University of Melbourne. M.J.W. and M.K.M. were supported by Research Fellowships from the NHMRC (APP1077703, APP1143224) .