Cerium Oxide Nanozymes Improve Skeletal Muscle Function in Gestational Diabetic Offspring by Attenuating
Xinyuan Li1,2,3, Wanbo Zhu4, Rui Liu1,2,3,5
1Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai200433,China.
Insights
Gestational diabetes mellitus (GDM) in offspring can cause skeletal muscle dysfunction. Cerium oxide nanozymes improve mitochondrial function and reverse these GDM-induced effects, enhancing muscle health.
Area of Science:
- Biomedical Engineering
- Mitochondrial Biology
- Developmental Biology
Background:
- Gestational diabetes mellitus (GDM) negatively impacts offspring's skeletal muscle and metabolism.
- Mitochondrial dysfunction and oxidative stress are key factors in GDM's intergenerational effects.
- Cerium oxide (CeO2) nanozymes possess antioxidant properties beneficial for inflammatory and aging diseases.
Purpose of the Study:
- To investigate the therapeutic potential of ultrasmall cerium oxide nanozymes in mitigating GDM-induced skeletal muscle abnormalities in offspring.
- To elucidate the mechanisms by which CeO2 nanozymes improve mitochondrial function and metabolic capacity in GDM offspring.
Main Methods:
- Synthesis of ultrasmall particle size cerium oxide (CeO2) nanozymes.
- Administration of CeO2 nanozymes to mouse offspring exposed to a high-glucose environment in utero.
- Assessment of skeletal muscle function, mitochondrial activity, ATP synthesis, morphology, and cellular metabolic profiles.
Main Results:
- CeO2 nanozymes enhanced insulin sensitivity and skeletal muscle motility in GDM offspring.
- Mitochondrial activity, ATP synthesis, and morphology were improved by CeO2 nanozymes.
- CeO2 nanozymes reduced oxidative stress by eliminating reactive oxygen species (ROS) and improved mitochondrial oxidative respiration.
- Metabolic dysregulation and impaired cell differentiation in adult muscle cells induced by hyperglycemia were ameliorated.
Conclusions:
- Ultrasmall CeO2 nanozymes effectively reverse the detrimental effects of GDM on skeletal muscle physiology in offspring.
- CeO2 nanozymes restore mitochondrial function and metabolic stability, preserving muscle health.
- These findings highlight the therapeutic promise of CeO2 nanozymes for GDM-related developmental complications.
Abstract:
Gestational diabetes mellitus (GDM) is a significant complication during pregnancy that results in abnormalities in the function of multiple systems in the offspring, which include skeletal muscle dysfunction and reduced systemic metabolic capacity. One of the primary causes behind this intergenerational effect is the presence of mitochondrial dysfunction and oxidative stress in the skeletal muscle of the offspring due to exposure to a high-glucose environment in utero. Cerium oxide (CeO2) nanozymes are antioxidant agents with polymerase activity that have been widely used in the treatment of inflammatory and aging diseases. In this study, we synthesized ultrasmall particle size CeO2 nanozymes and applied them in GDM mouse offspring. The CeO2 nanozymes demonstrated an ability to increase insulin sensitivity and enhance skeletal muscle motility in GDM offspring by improving mitochondrial activity, increasing mitochondrial ATP synthesis function, and restoring abnormal mitochondrial morphology. Furthermore, at the cellular level, CeO2 nanozymes could ameliorate metabolic dysregulation and decrease cell differentiation in adult muscle cells induced by hyperglycemic stimuli. This was achieved through the elimination of endogenous reactive oxygen species (ROS) and an improvement in mitochondrial oxidative respiration function. In conclusion, CeO2 nanozymes play a crucial role in preserving muscle function and maintaining the metabolic stability of organisms. Consequently, they serve to reverse the negative effects of GDM on skeletal muscle physiology in the offspring.
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