Biological Sciences Division
Published June 22, 2021 | Version v1
Journal article Open

Restored TDCA and valine levels imitate the effects of bariatric surgery

Creators

  • 1. Harvard University
  • 2. Beth Israel Deaconess Medical Center
  • 3. Charité Universitätsmedizin Berlin
  • 4. Osaka Medical and Pharmaceutical University
  • 5. Hannover Medical School
  • 6. University of Illinois at Chicago
  • 7. University of Chicago

Description

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 (SGx). In addition, mice were subjected to intraperitoneal (i.p.) injections with taurodeoxycholic acid (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 a melanin-concentrating hormone (MCH) antagonist and intrathecal administration of MCH 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 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 MCH.

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.

Notes

Due to the large number of authors, only the first 20 and the University of Chicago authors are included on the above author list. Please download the article for the complete list of authors.

Data availability

All relevant data supporting the findings of this study are available as source data files.

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Additional details

Identifiers

DOI
10.7554/eLife.62928
Other
oai:uchicago.tind.io:10062

Funding

National Institutes of Health
UO-1 A1 132898
Deutsche Forschungsgemeinschaft
QU 420/1-1
Deutsche Forschungsgemeinschaft
HE 7457/1-1
Deutsche Forschungsgemeinschaft
KR 4362/1-1
Chinese Scholarship Council
201606370196
German Research Foundation
DFG SFB738 B3
Osaka Medical Research Foundation for Intractable Diseases
European Society of Cardiology
German Academic Exchange Service
Boston Claude D. Pepper Older Americans Independence Center
5P30AG031679-10

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine