SAT054 LivARKO Female Mice On 1-month Of High Fat Diet (HFD) Did Not Experience Insulin Resistance At The Level Of p-AKT In WAT

Abstract

Abstract Disclosure: D.F. Curry: None. E. Bolarinwa: None. J.O. Hill-Dick: None. D. Young: None. R. Qutab: None. K. Carr: 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. The goal of this research was to determine if LivARKO prevents high fat diet (HFD) induced insulin resistance.It was hypothesized that (unlike HA-LivARKO) HFD LivARKO female mice would display impaired insulin action (lowered insulin-stimulated p-AKT) in white adipose tissue in comparison to the Control diet (CD) fed LivARKO female mice, suggesting that AR does not play a significant role in regulating HFD-induced insulin resistance. Female LivARKO mice were placed on two diets for 1 month: CD and HFD. The mice were then 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 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, this indicates malfunctioning insulin action or insulin resistance. Following a similar pattern as WT mice on a chow diet (White 2014, Fig. 4), insulin increased p-AKT in WAT of LivARKO female mice fed a CD for 1-month in comparison to LivARKO female mice not given insulin (basal). Following the pattern of WT mice on a HFD (White 2014), LivARKO female mice fed a HFD for 1-month, displayed a similar increase in insulin-stimulated p-AKT in the WAT compared to the Con-Ins group. p-IRS-1 was not detected in the WAT of LivARKO female mice fed a control diet or HFD. In conclusion, LivARKO female mice on 1-month of HFD were not experiencing insulin resistance at the level of p-AKT in WAT. Further studies in different energy storage tissues in this model are warranted. Presentation: Saturday, June 17, 2023