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Updated: May 14, 2026
The Creation of a Rat Model for Osteosarcopenia via Ovariectomy
Published on: February 21, 2025
Impaired PI3 K Akt expression in liver and skeletal muscle of ovariectomized rats
Yan Wang1, Baoxin Li, Wei Zhang
1Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China, wangyan0208@yahoo.cn.
Abstract:
It is well established that estrogen deficiency is strongly linked to the development of insulin resistance (IR), but the mechanism is still unclear. Since IR is characterized by a marked reduction in insulin-stimulated PI3 K-mediated activation of Akt in liver and skeletal muscle, we hypothesized that ovariectomized rats (OVX) would exhibit reductions in the expression of proteins in PI3 K signaling pathway, including PI3 K and Akt. As hypothesized, after observing for 12 weeks, compared with the SHAM rats, ovariectomy led to decreased plasma estrogen level and increased HOMA-IR index; in addition, ovariectomy also caused decreased PI3 K and Akt expression levels in the liver and skeletal muscle. Interestingly, the expression patterns differed in tissue-dependent fashion: Akt1 was only found reduction in liver, whereas Akt2 decreased in muscle; these changes can be reversed by estrogen supplement (OVXE). In conclusion, data demonstrate that estrogen withdrawals may cause IR at least in part by impaired PI3 K/Akt signaling proteins in liver and skeletal muscle, and Akt1 and Akt2 might be tissue-specific expressions.
Insights
Estrogen deficiency contributes to insulin resistance (IR) by impairing the PI3K/Akt signaling pathway in the liver and muscles. Estrogen therapy can reverse these effects, highlighting its role in metabolic health.
Area of Science:
- Endocrinology
- Metabolic Research
- Molecular Biology
Background:
- Estrogen deficiency is linked to insulin resistance (IR), but underlying mechanisms remain unclear.
- Insulin resistance involves reduced insulin-stimulated PI3K/Akt signaling in key metabolic tissues.
- Ovariectomy (OVX) is a model for studying estrogen deficiency effects.
Purpose of the Study:
- To investigate the impact of estrogen deficiency on the PI3K/Akt signaling pathway.
- To determine if ovariectomy in rats affects PI3K and Akt protein expression.
- To assess the reversibility of these changes with estrogen supplementation.
Main Methods:
- Ovariectomized (OVX) and sham-operated (SHAM) rats were used.
- Plasma estrogen levels and HOMA-IR index were measured.
- PI3K and Akt protein expression in liver and skeletal muscle were analyzed via Western blotting.
- Effects of estrogen supplementation (OVXE) were evaluated.
Main Results:
- OVX rats showed decreased plasma estrogen and increased HOMA-IR compared to SHAM rats.
- Ovariectomy reduced PI3K and Akt expression in liver and skeletal muscle.
- Akt1 reduction was observed in the liver, while Akt2 decreased in skeletal muscle.
- Estrogen supplementation reversed these molecular and metabolic changes.
Conclusions:
- Estrogen deficiency impairs insulin sensitivity, at least partly, by inhibiting PI3K/Akt signaling in liver and skeletal muscle.
- Akt1 and Akt2 exhibit tissue-specific expression patterns and roles in estrogen-mediated insulin signaling.
- Estrogen replacement therapy holds potential for managing insulin resistance associated with estrogen deficiency.
