Liver Androgen Receptor Knockout Delayed the Onset of High Fructose Diet-Induced Dysglycemia in Female Mice

Abstract

Introduction: Previous research has indicated that a lipid-independent pathogenic mechanism plays a role in androgen-induced hepatic insulin resistance where liver androgen receptors may play a role in modulating disease. Consequently, this study aims to investigate the pathophysiology of high fructose diet (HFrD) induced dysglycemia in male and female liver androgen receptor knockout (LivARKO) mice. Andrisse et al 2021 showed that deleting the liver androgen receptor prevented female mice from developing hyperandrogenemia (HA)-induced insulin resistance. From this, we asked the question, does LivARKO prevent HFrD induced dysglycemia? Hypothesis: It was hypothesized that HFrD LivARKO female mice would display impaired whole body glucose metabolism in comparison to the Control diet fed LivARKO female mice, suggesting that AR does not play a significant role in regulating HFrD-induced dysglycemia.Methods: We performed insulin tolerance tests (ITT), glucose tolerance tests (GTT), pyruvate tolerance tests (PTT), and glucose stimulated insulin secretion (GSIS) tests on LivARKO female mice fed a high fat diet (HFD) or a control diet (CD) (from Research Diets Inc) during months 1 or 2 after starting the diet. Results: After 1-month, LivARKO female mice fed a Control diet had impaired glucose tolerance compared to LivARKO-HFrD female mice; however, after 2-months, the LivARKO-HFrD female mice displayed impaired glucose tolerance above that of the Control diet LivARKO female mice. LivARKO female mice fed a high fructose diet (HFrD) did not display increased fasting insulin levels compared to LivARKO female mice on a control diet. HFrD LivARKO mice did not display any increase in GSIS at 15-min or 30-min. Conclusion: These findings suggest that LivARKO delayed the onset of HFrD-Induced dysglycemia in female mice. Further research may consist of molecular data to elucidate the mechanistic pathways involved in these whole body phenotypes observed. The cellular molecular regulation of differing mechanisms of insulin resistance. 1R01DK126892-01A1 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.