Restored TDCA and valine levels imitate the effects of bariatric surgery
- Brigham and Women's Hospital, United States
- Beth Israel Deaconess Medical Center, United States
- Charité Universitätsmedizin Berlin, Germany
- Osaka Medical College, Japan
- Hannover Medical School, Germany
- University of Illinois at Chicago, United States
- Beth Israel Deaconess Medical Center and Harvard Medical School, United States
Abstract
Background: 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.
Methods: Metabolic profiling was performed on diet induced obese (DIO) mice, lean mice and DIO mice that underwent sleeve gastrectomies. In addition, mice were subjected to i.p. injections with TDCA and valine. Indirect calorimetry was performed to assess food intake and energy expenditure. Expression of appetite regulating hormones was assessed through quantification of isolated RNA from dissected hypothalamus tissue. Subsequently, i.p. injections with an MCH antagonist and intrathecal administration of melanin-concentrating hormone were performed and weight loss was monitored.
Results: Mass-spectrometric metabolomic profiling revealed significantly reduced systemic levels of TDCA and L-valine in DIO mice. TDCA and L-Valine levels were restored after sleeve gastrectomies (SGx) in both human and mice to levels comparable with lean controls. Systemic treatment with TDCA and valine induced a profound weight loss 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.
Conclusions: 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.
Data availability
All relevant data supporting the findings of this study are available as source data files.
Article and author information
Author details
Funding
National Institutes of Health (UO-1 A1 132898)
- Stefan G Tullius
Deutsche Forschungsgemeinschaft (QU 420/1-1)
- Markus Quante
Deutsche Forschungsgemeinschaft (HE 7457/1-1)
- Timm Heinbokel
Deutsche Forschungsgemeinschaft (KR 4362/1-1)
- Felix Krenzien
Chinese Scholarship Council (201606370196)
- Yeqi Nian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal use and care were in accordance with institutional and National Institutes of Health guidelines. The study protocol was approved by the Brigham and Women´s Hospital Institutional Animal Care and use Committee (IACUC) animal protocol (animal protocol 2016N000371).
Human subjects: Serum samples from patients prior to and 3 months post sleeve gastrectomy were obtained with approval of the Brigham and Women's Hospital (BWH) Institutional Review Board and through cooperation with Dr. Eric G. Sheu and the Center for Metabolic and Bariatric Surgery at BWH. Informed consent was obtained from all patients and samples were collected following BWH ethical regulations.
Reviewing Editor
- Ralph J DeBerardinis, UT Southwestern Medical Center, United States
Version history
- Received: September 9, 2020
- Accepted: May 20, 2021
- Accepted Manuscript published: June 22, 2021 (version 1)
- Version of Record published: July 5, 2021 (version 2)
Copyright
© 2021, Quante et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Restored TDCA and valine levels imitate the effects of bariatric surgery
eLife 10:e62928.
https://doi.org/10.7554/eLife.62928
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