Hepatic ERα contributes to preserve metabolic homeostasis in the liver of females under an excess of dietary lipids. (A) HFD effects on metabolite–metabolite interaction in the liver of control males, control females, LERKO males, and LERKO females. (B) Metabolic impact analysis of the most relevant biological pathways modified by HFD in the livers of control males, control females, LERKO males, and LERKO females identified through integrative analysis of the changes in the expression of key genes and metabolites. The metabolic pathways are represented as circles according to their enrichment (p-value, Y axis) and topology analyses (pathway impact, X axis) using MetaboAnalyst 5.0 software. The color of each metabolic pathway is related to the p-value obtained from enrichment analysis and its size represents the fold enrichment score; darker circle colors indicate more significant changes of metabolites in the corresponding pathway. The size of the circle corresponds to the pathway impact score and is correlated with the centrality of the involved metabolites.