ESR1 and metabolic disease: Additional studies will be needed to clearly define how hepatic ERα modulates Pomc and/or AgRP/NPY neuronal activity, but an emerging body of literature indicates that 17β-E2, likely through ERα, beneficially modulates vagal afferent signaling in the gut-brain-liver axis [132-135]; highlighting this pathway as a potential therapeutic target for mitigating aging and metabolic diseases.