MON-268 Liver Androgen Receptor Knockout Does Not Protect Against High-Fructose Diet-Induced Glucose Dysregulation in Female Mice

Abstract Disclosure: M.A. Rahman: None. S. Andrisse: None. The liver androgen receptor (AR) plays a crucial role in metabolic regulation, particularly under dietary stress. This study examined the impact of a high-fructose diet (HFrD) on glucose metabolism in male and female liver androgen receptor knockout (LivARKO) mice. LivARKO and wild-type (WT) mice were fed either an HFrD or a control diet, and glucose tolerance and insulin sensitivity were assessed over two months. In female mice, LivARKO did not prevent HFrD-induced glucose intolerance, as LivARKO-HFrD females exhibited similar impairments in glucose tolerance as their WT counterparts. While insulin sensitivity improved slightly in LivARKO females at later time points, they displayed significant hyperinsulinemia relative to controls. In contrast, male LivARKO mice experienced exacerbated glucose intolerance and heightened hepatic insulin resistance under HFrD conditions, suggesting sex-specific effects of hepatic AR loss on metabolic function. These findings indicate that liver AR knockout does not protect against HFrD-induced metabolic dysfunction in females and may worsen glucose homeostasis in males, highlighting the differential role of AR in diet-induced metabolic dysregulation. Presentation: Monday, July 14, 2025