Furthermore, a parallel decrease in liver ghrelin level in Mito-Ob mice during disease progression as observed in this study may be due to a sex-dimorphic effect of PHB on ghrelin production from macrophages, as macrophages are known to produce ghrelin47, which in turn contribute to the development of NASH and HCC in male Mito-Ob mice and confer a protection in female mice. This evidence concerns the gene GHRL and metabolic dysfunction-associated steatohepatitis.