Objective:

To examine the physiological response to reduced gravity and inactivity, focusing on metabolic disorders such as obesity, insulin resistance, and related liver and pancreatic conditions, and their implications for health on Earth.

Key Findings:

• Mechanical load deprivation alters fat distribution and promotes visceral adiposity, with implications for metabolic health.
• Initiates inflammation and immune-metabolic reprogramming, highlighting potential pathways for intervention.
• Emerging countermeasures include vibration platforms and resistive suits, which may mitigate adverse effects.
• A proposed 12-week cascade model illustrates disease progression under reduced mechanical loading, providing a framework for future research.

Interpretation:

Microgravity serves as a translational model to enhance understanding of lifestyle-induced metabolic disorders, providing insights into the mechanisms of inactivity-related diseases and their potential treatments.

Limitations:

• Heterogeneity of study designs and outcomes may affect synthesis of findings, limiting the robustness of conclusions.
• Limited generalizability of spaceflight data to broader populations, necessitating caution in applying findings to Earth-based conditions.

Conclusion:

The review highlights the importance of microgravity in understanding and potentially mitigating metabolic disorders associated with sedentary lifestyles on Earth.