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Restored TDCA and Valine Levels Imitate the Effects of Bariatric Surgery
bioRxiv - Cell Biology Pub Date : 2021-01-12 , DOI: 10.1101/2021.01.11.425291
Markus Quante , Jasper Iske , Timm Heinbokel , Bhavna N. Desai , Hector Rodriguez Cetina Biefer , Yeqi Nian , Felix Krenzien , Hirofumi Uehara , Ryoichi Maenosono , Haruhito Azuma , Johann Pratschke , Christine Falk , Tammy Lo , Eric Sheu , Ali Tavakkoli , David Perkins , Maria-Luisa Alegre , Alexander S. Banks , Abdallah Elkhal , Stefan G. Tullius

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. Mass-spectrometric metabolomic profiling revealed significantly reduced systemic levels of TDCA and L-valine in Diet-Induced-Obese (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. 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.

中文翻译:

恢复的TDCA和缬氨酸水平可模拟减肥手术的效果

肥胖是普遍存在的并且与各种合并症相关。减肥手术已被认为是唯一有效的疗法,可促进持续的体重减轻和合并症的缓解。质谱代谢组学分析显示,饮食诱导肥胖(DIO)小鼠的TDCA和L-缬氨酸的全身水平显着降低。在人和小鼠的袖子胃切除术(SGx)后,TDCA和L-缬氨酸水平恢复到与瘦对照相当的水平。TDCA和缬氨酸的全身性治疗可导致严重的体重减轻,类似于SGx后观察到的效果。利用间接量热法,我们证实食物摄入减少是通过黑色素浓缩激素的中枢抑制导致TDCA /缬氨酸介导的体重减轻的原因。综上所述,我们将恢复的TDCA /缬氨酸水平确定为SGx衍生的减肥作用的潜在机制。在翻译相关性方面,TDCA和L-缬氨酸被认为是新型药物,可促进体重减轻,同时还可逆转肥胖相关的代谢性疾病。
更新日期:2021-01-12
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