This project aims to explore how Sirtuin 3 (Sirt3) and sex hormones collaborate to mitigate metabolic stress induced by a Western diet, focusing on the adipose tissue-liver crosstalk in the context of obesity-related diseases. Understanding these interactions is crucial given the global prevalence of obesity and its associated health challenges. The research utilizes advanced genetic, molecular, and imaging technologies, along with metabolomic analyses, incorporating preclinical cell cultures, mouse models, and clinical studies to decipher Sirt3's role in sex-specific susceptibility to metabolic complications linked to obesity.