Pathway Preferential Estrogens prevent hepatosteatosis due to ovariectomy and high-fat diets

Pathway preferential estrogen 1 (PaPE-1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE-1 on metabolic health, in particular, examin-ing its effects on the liver transcriptome and on plasma metabolites in two different mouse mod-els: diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice. PaPE-1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. Overall, our findings support a beneficial metabolic role for PaPE-1 and suggest that PaPE-1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.