SAT055 The Effect Of High Fat Diet On Insulin Signaling In White Adipose Tissue Of Liver Androgen Receptor Knockout In Female Mice

Abstract Disclosure: E. Bolarinwa: None. D. Young: None. J.O. Hill-Dick: None. D.F. Curry: None. K. Carr: None. R. Qutab: None. C. Falzarano: None. S. Andrisse: None. 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 (HA)-induced insulin resistance. This study places female LivARKO mice on high fructose diets (HFrD) to determine if LivARKO mice demonstrate blunted insulin resistance on HFrD compared to control diet. It was hypothesized that (unlike HA-LivARKO) HFrD LivARKO female mice would display impaired insulin action (lowered insulin-stimulated p-AKT) in white adipose tissue in comparison to the Control diet fed LivARKO female mice, suggesting that AR does not play a significant role in regulating HFrD-induced insulin resistance. Female LivARKO mice were placed on two diets: Control (Con, Research Diets Inc, RDI D12450J) and High Fructose (HFrD, RDI D02022704). After 3 months on the diet, the mice were sacrificed. 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 (WAT). BCA assays were used to standardize the protein concentration in each sample. Insulin action can be measured molecularly by examining p-AKT Serine 473 (positive regulator, Santa Cruz sc-514032) and p-IRS1 Serine 306 (negative regulator, Santa Cruz sc-33956). If p-AKT S473 levels increase in the presence of insulin, this indicates that insulin is likely functioning properly in the sample. Whereas if p-IRS1 S306 are elevated, indicating malfunctioning insulin action or resistance. LivARKO female mice fed a chow or control diet for 3-months displayed no expression of basal or insulin stimulated p-AKT. LivARKO female mice fed a HFrD for 3-months displayed elevated AKT and similar p-AKT in WAT of HFrD Insulin mice compared to HFrD Basal treated mice. p-IRS1 was not detected in Control or HFrD female LivARKO mice. In conclusion, these data suggest that LivARKO indirectly disrupted insulin-stimulated p-AKT in WAT possibly via altering metabolites in the blood. Additionally, HFrD is known to cause insulin resistance, however, it is not known to alter p-AKT levels. Thus, the change in p-AKT levels is presumably associated with the LivARKO. Further research is required on what components of the Control Diet are prompting this difference in insulin action and if it only takes place in the LivARKO mouse model. Presentation: Saturday, June 17, 2023