@article{TEXTUAL,
      recid = {10062},
      author = {Quante, Markus and Iske, Jasper and Heinbokel, Timm and  Desai, Bhavna N. and Rodriguez Cetina Biefer, Hector and  Nian, Yeqi and Krenzien, Felix and Matsunaga, Tomohisa and  Uehara, Hirofumi and Maenosono, Ryoichi and Azuma, Haruhito  and Pratschke, Johann and Falk, Christine S. and Lo, Tammy  and Sheu, Eric and Tavakkoli, Ali and Abdi, Reza and  Perkins, David and Alegre, Maria-Luisa and Banks, Alexander  S.},
      title = {Restored TDCA and valine levels imitate the effects of  bariatric surgery},
      journal = {eLife},
      address = {2021-06-22},
      number = {TEXTUAL},
      abstract = {&lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt;},
      url = {http://knowledge.uchicago.edu/record/10062},
}