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Polysorbate 80-induced leaky gut impairs skeletal muscle metabolism in mice
Saho Nishimura1,2, Wataru Aoi1, Hinako Kodani1
1Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
Abstract:
Impaired intestinal permeability can induce systemic inflammation and metabolic disturbance. However, the effect of impaired intestinal permeability on metabolic function in the skeletal muscle is unknown. Dietary polysorbate 80 (PS80), a common emulsifier, has been shown to impair intestinal permeability in mice. Here, we investigated the effect of PS80-induced intestinal permeability on glucose tolerance with metabolic signaling in the skeletal muscle. Male ICR mice were divided into control and PS80 groups. In the PS80 group, PS80 was contained in the drinking water at 1% (w/v). After 4 weeks, plasma fluorescein isothiocyanate (FITC) intensity was measured after orally administering FITC-dextran. Half of the mice in each group underwent running exercises. Metabolic and inflammatory parameters were examined in the blood and skeletal muscle. Plasma FITC and lipopolysaccharide levels were higher in the PS80 group than the control group (p < .01, p = .085). The expression of tumor necrosis factor-α in the skeletal muscle was increased upon PS80 administration (p < .05). Although the homeostasis model assessment ratio was higher in the PS80-fed mice (p < .05), insulin-signaling activity in the muscle did not differ between groups. Muscular pH, mitochondrial cytochrome oxidase activity, and glycogen content after exercise were lower in the PS80 group (p < .05) than the control group. There was a negative correlation between plasma FITC and muscle glycogen levels in the exercised groups (r = -.60, p < .05). These results suggest that daily PS80 intake induces intestinal permeability, leading to glucose intolerance and mitochondrial dysfunction in the skeletal muscle.
Insights
Dietary polysorbate 80 (PS80) impairs intestinal permeability, leading to glucose intolerance and mitochondrial dysfunction in skeletal muscle. This emulsifier negatively impacts muscle energy metabolism and exercise performance.
Area of Science:
- Metabolic Physiology
- Gastroenterology
- Exercise Science
Background:
- Impaired intestinal permeability is linked to systemic inflammation and metabolic disorders.
- The specific impact of compromised gut barrier function on skeletal muscle metabolism remains unclear.
- Dietary polysorbate 80 (PS80), a common emulsifier, is known to disrupt intestinal permeability in animal models.
Purpose of the Study:
- To investigate the effects of PS80-induced intestinal permeability on glucose tolerance.
- To examine the impact on metabolic signaling pathways within skeletal muscle.
- To assess the consequences for muscle function, particularly after exercise.
Main Methods:
- Male ICR mice were administered PS80 in drinking water for 4 weeks.
- Intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran.
- Mice underwent running exercises, followed by analysis of blood and skeletal muscle for metabolic and inflammatory markers.
Main Results:
- PS80 ingestion increased plasma levels of FITC and lipopolysaccharide, indicating heightened intestinal permeability.
- Skeletal muscle showed increased tumor necrosis factor-α expression and impaired mitochondrial function (reduced pH, cytochrome oxidase activity, and post-exercise glycogen).
- Despite increased insulin resistance markers, direct insulin signaling in muscle was unaffected, but glucose intolerance and reduced exercise capacity were observed.
Conclusions:
- Daily intake of PS80 induces intestinal permeability, contributing to glucose intolerance.
- PS80 negatively affects skeletal muscle mitochondrial function and energy reserves.
- These findings highlight a link between dietary emulsifiers, gut health, and skeletal muscle metabolic disturbances.
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