Knockout of Liver Androgen Receptor in Female Mice Did Not Prevent High-Fructose Diet Induced Glucose Dysregulation

Previous research has highlighted the role of liver androgen receptors in metabolic regulation under dietary stress. This study investigated the effects of high-fructose diet (HFrD) on glucose regulation in male and female liver androgen receptor knockout (LivARKO) mice. LivARKO and wild-type mice were fed an HFrD or control diet, and glucose tolerance and insulin sensitivity were assessed during months 1 and 2. LivARKO-HFrD female mice exhibited impaired glucose tolerance similar to their wild-type counterparts, indicating that LivARKO did not protect against HFrD-induced glucose dysregulation in females. While LivARKO-HFrD females showed slightly improved insulin sensitivity at later time points, they exhibited significant hyperinsulinemia compared to controls. In male mice, LivARKO exacerbated glucose intolerance under HFrD conditions, and LivARKO-HFrD males displayed pronounced hepatic insulin resistance compared to females. These findings suggest that LivARKO does not mitigate HFrD-induced metabolic dysfunction in females and may worsen outcomes in males, emphasizing diet-specific mechanisms of androgen receptor involvement in glucose homeostasis. We would like to thank the National Science Foundation for award NSF1931045 and the National Institutes of Health for award 1R01DK126892-01A1. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.