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With increasing severity of NASH and fibrosis, BA levels tend to increase and the composition of BAs changes, which may partly result from insulin resistance,89 impaired hepatobiliary excretory function1820 and altered microbial BA metabolism caused by NASH-associated dysbiosis.55 Despite increased BA levels, FXR and FGF19 signalling is impaired, resulting in increased BA synthesis90 91 and BA toxicity could contribute to the hepatocellular injury and even carcinogenesis in NASH.4 12 92 Thus, restoration of FXR signalling and BA and lipid homoeostasis may explain at least part of the therapeutic effects of FXR ligands in NAFLD/NASH

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ATPase Inhibitory Factor 1 (IF1) is a low molecular weight (~10 kDa) mitochondrial protein which acts as a natural inhibitor of ATP synthase, but does not interfere with its coupling activity (Cabezon et al., 2012)