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SAT051 The Effect Of High Fat Diet On Insulin Signaling In White Adipose Tissue Of Liver Androgen Receptor Knockout In Male Mice
Disclosure: J.O. Hill-Dick: None. D. Young: None. D. Curry: None. E. Bolarinwa: None. R. Qutab: None. K. Carr: None. C. Falzarano: None. S. Andrisse: None. Insulin resistance affects up to 33% of the US adult population and polycystic ovary syndrome affects up to 10% of reproductive-age adult women....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10554919/ http://dx.doi.org/10.1210/jendso/bvad114.919 |
Sumario: | Disclosure: J.O. Hill-Dick: None. D. Young: None. D. Curry: None. E. Bolarinwa: None. R. Qutab: None. K. Carr: None. C. Falzarano: None. S. Andrisse: None. Insulin resistance affects up to 33% 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 role in the metabolism of insulin and androgen signaling. Hyperandrogenism in females can increase their predisposition to insulin resistance. It has been previously shown 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 fructose diet (HFrD) induced insulin resistance. It was hypothesized that HFrD LivARKO male mice would display impaired insulin action 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. Male LivARKO mice were placed on either a control (Research Diets Inc, RDI D12450J) or High Fructose (HFrD, RDI D02022704) diet and sacrificed after 1 month. Half of the mice were given 0.5 U/kg of insulin before being sacrificed 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) standardized using BCA assays. LivARKO male mice fed a chow or control diet for 1 month displayed no or low expression of p-AKT in the basal and insulin-stimulated state, suggesting that LivARKO had an indirect effect on insulin-stimulated signaling in WAT. Oddly, LivARKO male mice fed a HFrD displayed increased insulin-stimulated p-AKT compared to basal, suggesting functional insulin-stimulated p-AKT. This increased p-AKT may be a compensatory mechanism as HFrD is known to disrupt glucokinase and glycogen synthase. In normal physiology, on a chow diet, insulin should increase p-AKT. The data shows that in male LivARKO mice, insulin did not increase p-AKT in chow, control, or HFrD, suggesting that the male LivARKO mice are experiencing insulin resistance at the level of p-AKT in WAT. 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 into 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 |
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