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Gravity as a key player for the preservation of muscle mass and function in the era of anti-obesity therapies?

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Novel anti-obesity medications and obesity surgery to treat obesity demonstrated very good efficacy on weight management but their impact on body composition is still debated -particularly the disproportionate loss of lean mass, including skeletal muscle. Muscle mass decline is not only a concern for mobility and quality of life, but also a key driver of metabolic adaptation and for the prevention of long-term weight regain. We propose that the role of mechanical loading-specifically gravitational force-has been largely overlooked in this context. Drawing from emerging evidence and the concept of "gravitostat," we discuss how external loading strategies, such as weighted vests, could help preserve muscle mass and mitigate compensatory energy responses during weight loss. These insights suggest a "homeogravitational" approach that maintains mechanical stimuli even as fat mass declines, offering a novel strategy to improve the quality and sustainability of weight loss. In the era of incretin-based therapies, reintroducing gravity into the conversation may be both physiologically and clinically relevant.

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