Restored TDCA and Valine Levels Imitate the Effects of Bariatric Surgery

Tullius, S. G.; Quante, M.; Iske, J.; Heinbokel, T.; Desai, B. N.; Biefer, H. R. C.; Nian, Y.; Krenzien, F.; Uehara, H.; Maenosono, R.; Azuma, H.; Pratschke, J.; Falk, C.; Lo, T.; Sheu, E.; Tavakkoli, A.; Perkins, D.; Alegre, M.-L.; Banks, A. S.; Elkhal, A.

doi:10.1101/2021.01.11.425291

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bioRxiv · 10.1101/2021.01.11.425291

Restored TDCA and Valine Levels Imitate the Effects of Bariatric Surgery

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Abstract

Obesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities. We performed sleeve-gastrectomies (SGx) in a pre-clinical mouse model of diet-induced obesity (DIO), delineating the effects on long-term remission from obesity. SGx resulted in sustained weight loss and improved glucose tolerance. Mass-spectrometric metabolomic profiling revealed significantly reduced systemic levels of taurodeoxycholic acid (TDCA) and L-valine in DIO mice. Notably, TDCA and L-Valine levels were restored after SGx in both human and mice to levels comparable with lean controls. Strikingly, combined systemic treatment with TDCA and valine induced a profound weight loss in DIO mice analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the melanin-concentrating hormone. In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders.

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Tullius, S. G., Quante, M., Iske, J., Heinbokel, T., Desai, B. N., Biefer, H. R. C., Nian, Y., Krenzien, F., Uehara, H., Maenosono, R., Azuma, H., Pratschke, J., Falk, C., Lo, T., Sheu, E., Tavakkoli, A., Perkins, D., Alegre, M.-L., Banks, A. S., Elkhal, A.. 2021-01-12. Restored TDCA and Valine Levels Imitate the Effects of Bariatric Surgery. https://doi.org/10.1101/2021.01.11.425291

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