FRI024 The Effect Of High Fat Diet On Insulin Signaling In White Adipose Tissue Of Liver Androgen Receptor Knockout In Female Mice

Disclosure: D. Young: None. Introduction: Insulin resistance affects up to a third of the US adult population and polycystic ovary syndrome affects up to 10% of reproductive-age adult women. The liver and white adipose tissue play an essential component in the metabolism of insulin and androgen signaling. Hyperandrogenism in females can increase predisposition to insulin resistance. Andrisse et al 2021 showed that deleting the liver androgen receptor (LivARKO) prevented female mice from developing hyperandrogenemia-induced insulin resistance. We wanted to know does LivARKO prevent high fructose diet (HFrD) induced insulin resistance? In our study, we placed female LivARKO mice on high fructose diets (HFrD) to determine if they demonstrated blunted insulin resistance. We hypothesized was that HFrD LivARKO female mice would display impaired insulin action in white adipose tissue. We needed to demonstrate that insulin signaling was functional in LivARKO mice on a control and a HFrD. There are six groups in this study: wild type (WT) no treatment, WT treatment-1, WT treatment-2, LivARKO no treatment, LivARKO treatment-1, and LivARKO treatment-2. No treatment is a chow diet, treatment-1 is a control diet, and treatment-2 is HFrD. Methods: Female LivARKO mice were placed on two diets: Control (Con, Research Diets Inc, RDI D12450J and High Fructose (HFrD, RDI D02022704. The mice were sacrificed after 1 month on the diet. Half of the mice were given a dose of 0.5 U/kg insulin before sacrificing to investigate the effects of the diets on insulin signaling. Western blots were used to determine protein expression in tissue from the white adipose tissue. BCA assays were used to standardize the protein concentration in each sample. Insulin action was measured molecularly by examining p-AKT Serine 473 ( Santa Cruz sc-514032) and p-IRS1 Serine 306 ( Santa Cruz sc-33956). If p-AKT S473 levels increase in the presence of insulin, indicating that insulin is likely functioning properly. If p-IRS1 S306 are elevated, indicates malfunctioning insulin or resistance. Results: LivARKO Female mice on a control diet did not express any insulin stimulated p-AKT in WAT, LivARKO Female mice on a high fructose diet displayed increased insulin stimulated p-AKT compared to LivARKO HFrD mice not given insulin. P-IRS1 was increased in the WAT of the Control Insulin group compared to the WAT of the Control Basal group of female LivARKO mice. Once placed on a HFrD, p-IRS1 was not present in the WAT either group of LivARKO mice. Conclusion: In conclusion, the data is inconclusive. HFrD appeared to augment insulin-stimulated p-AKT but lowered p-IRS1 in WAT of female LivARKO mice. There were several limitations to this study. We do not have data for LivARKO on chow or data for WT on control diet to decipher these effects. Further research is required into what components of the Control Diet are prompting this difference in insulin action. Presentation: Friday, June 16, 2023