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Oral anserine supplementation does not attenuate type-2 diabetes or diabetic nephropathy in BTBR ob/ob mice

Abstract

Carnosine, a naturally occurring dipeptide present in an omnivorous diet, has been shown to ameliorate the development of metabolic syndrome, type-2 diabetes (T2D) and early- and advanced-stage diabetic nephropathy in different rodent models. Anserine, its methylated analogue, is more bio-available in humans upon supplementation without affecting its functionality. In this work, we investigated the effect of oral supplementation with anserine or carnosine on circulating and tissue anserine and carnosine levels and on the development of T2D and diabetic nephropathy in BTBR ob/ob mice. BTBR ob/ob mice were either supplemented with carnosine or anserine in drinking water (4 mM) for 18 weeks and compared with non-supplemented BTBR ob/ob and wild-type (WT) mice. Circulating and kidney, but not muscle, carnosine, and anserine levels were enhanced by supplementation with the respective dipeptides in ob/ob mice compared to non-treated ob/ob mice. The evolution of fasting blood glucose, insulin, fructosamine, triglycerides, and cholesterol was not affected by the supplementation regimens. The albumin/creatine ratio, glomerular hypertrophy, and mesangial matrix expansion were aggravated in ob/ob vs. WT mice, but not alleviated by supplementation. To conclude, long-term supplementation with anserine elevates circulating and kidney anserine levels in diabetic mice. However, anserine supplementation was not able to attenuate the development of T2D or diabetic nephropathy in BTBR ob/ob mice. Further research will have to elucidate whether anserine can attenuate milder forms of T2D or metabolic syndrome.

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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The (technical) assistance of the animal caretakers, Clinical lab of University Hospital UZ Ghent and Anneke Volkaert is greatly acknowledged. The lab of Chemical Analysis research group is part of the Ghent University expertise centre MSsmall. We thank Flamma for providing the carnosine and anserine.

Funding

This study was financially supported by grants from Special Research Fund of Ghent University. IE is a recipient of a post-doctoral scholarship by the Research Foundation—Flanders (FWO).

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Authors and Affiliations

Authors

Contributions

IE and WD designed the study. IE, TVDS, JS, MH, CVA, and HB performed research. IE, TVDS, JS, CVA and HB analyzed the data. IE, TVDS, JS, MH, HB, LV, and WD wrote the paper.

Corresponding author

Correspondence to Inge Everaert.

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The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical approval

The experimental protocol was approved by the Ethics Committee for Animal Research at Ghent University and followed the Principles of Laboratory Animal Care.

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Handling editor: G. J. Peters.

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Everaert, I., Van der Stede, T., Stautemas, J. et al. Oral anserine supplementation does not attenuate type-2 diabetes or diabetic nephropathy in BTBR ob/ob mice. Amino Acids 53, 1269–1277 (2021). https://doi.org/10.1007/s00726-021-03033-4

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  • DOI: https://doi.org/10.1007/s00726-021-03033-4

Keywords

  • Carnosine
  • Anserine
  • Diabetes
  • Diabetic nephropathy
  • BTBR ob/ob mice