Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

Hunter, Harriet, Cambridge School

de Gracia Hahn, Dana, Cambridge School

Duret, Amedine, Cambridge School

Im, Yu Ri, Cambridge School

Cheah, Qinrong, Cambridge School

Dong, Jiawen, Cambridge School

Fairey, Madison, Cambridge School

Hjalmarsson, Clarissa, Cambridge School

Li, Alice, Cambridge School

Lim, Hong Kai, Cambridge School, https://orcid.org/0000-0002-7266-7790

McKeown, Lorcan, Cambridge School

Mitrofan, Claudia-Gabriela, Cambridge School

Rao, Raunak, Cambridge School

Utukuri, Mrudula, Cambridge School

Rowe, Ian A, University of Leeds

Mann, Jake, University of Cambridge, https://orcid.org/0000-0002-4711-9215

hattiehunter@doctors.org.uk, jm2032@cam.ac.uk

Published Oct 16, 2020 on Dryad. https://doi.org/10.5061/dryad.pzgmsbcgc

Cite this dataset

Hunter, Harriet et al. (2020). Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver [Dataset]. Dryad. https://doi.org/10.5061/dryad.pzgmsbcgc

Abstract

The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however there is a low conversion rate from success in animals to humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any established therapies and a major field of animal research. We performed a meta-analysis with meta-regression of 603 interventional rodent studies (10,364 animals) in NAFLD to assess which variables influenced treatment response. Weight loss and alleviation of insulin resistance were consistently associated with improvement in NAFLD. Multiple drug classes that do not affect weight in humans caused weight loss in animals. Other study design variables, such as age of animals and dietary composition, influenced the magnitude of treatment effect. Publication bias may have increased effect estimates by 37-79%. These findings help to explain the challenge of reproducibility and translation within the field of metabolism.

Usage notes

This dataset can be analysed using the added code for R 4.0.2.

See README file.

Funding

Wellcome Trust, Award: 216329/Z/19/Z

European Society for Paediatric Research, Award: Young Investigator Start-Up Grant