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Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats

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Abstract

Purpose

Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits.

Methods

The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet.

Results

Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r 2 = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r 2 = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses.

Conclusion

Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.

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Abbreviations

LBP:

Lipopolysaccharide binding protein

LGI:

Low-grade inflamed

NAC:

N-acetyl cysteine

NI:

Non-inflamed

sTNFR-1:

Soluble tumour necrosis factor-alpha receptor-1

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Acknowledgments

The authors would like to acknowledge Marie Perrot for help in the statistical analysis, Jacques Vuichoud for the determination of amino acids in the standard diet, the Staff of the Unité Expérimentale de Nutrition Comparée for animal care, and Viral Vishnuprasad Brahmbhatt (Nestlé Research Center) for improving the manuscript. This work was supported by Institut National de la Recherche Agronomique (INRA), France, and Nestlé, Switzerland.

Conflict of interest

K. Vidal, D. Breuillé, and P. Serrant are employees of Nestec Ltd. K. Vidal, D. Breuillé, and I. Papet are co-inventors on a patent related to the present study. P. Denis, F. Glomot, and F. Béchereau declare no conflict of interest.

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Correspondence to Isabelle Papet.

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Vidal, K., Breuillé, D., Serrant, P. et al. Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats. Eur J Nutr 53, 963–971 (2014). https://doi.org/10.1007/s00394-013-0600-0

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  • DOI: https://doi.org/10.1007/s00394-013-0600-0

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