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An integrated understanding of the molecular mechanisms how adipose tissue metabolism affects long-term body weight maintenance

Item Type:Article
Title:An integrated understanding of the molecular mechanisms how adipose tissue metabolism affects long-term body weight maintenance
Creators Name:Mai, K. and Li, L. and Wiegand, S. and Brachs, M. and Leupelt, V. and Ernert, A. and Kühnen, P. and Hübner, N. and Robinson, P. and Chen, W. and Krude, H. and Spranger, J.
Abstract:Life-style based weight loss interventions frequently demonstrate long-term inefficiency and weight regain. Identification of underlying mechanisms and predictors to identify subjects who will benefit from life-style based weight loss strategies is urgently required. We analyzed 143 adults of the randomized Maintain trial (Maintain-Adults) after intended weight loss to identify mechanisms contributing to the regulation of body weight maintenance. Unbiased RNA sequencing of adipose and skeletal muscle biopsies revealed fatty acid metabolism as a key pathway modified by weight loss. Variability of key enzymes of this pathway, estimates of substrate oxidation and specific serum acylcarnitine (AC) species, representing a systemic snapshot of in vivo substrate flux, predicted body weight maintenance (defined as continuous or dichotomized (</≥3% weight regain) variable) 18 months after intended weight loss in the entire cohort. Key results were confirmed in a similar RCT in 137 children and adolescents (Maintain-Children), which investigated the same paradigm in a pediatric cohort. These data suggest that adaption of lipid utilization in response to negative energy balance contributes to subsequent weight maintenance. Particularly a functional role for circulating ACs, which have been suggested to reflect intracellular substrate utilization, as mediators between peripheral energy stores and control of long-term energy homeostasis was indicated.
Keywords:Obesity, Weight Loss Maintenance, Adipose Tissue, Lipid Flux, mRNA Expression Profiling
Source:Diabetes
ISSN:0012-1797
Publisher:American Diabetes Association (U.S.A.)
Volume:68
Number:1
Page Range:57-65
Date:1 January 2019
Official Publication:https://doi.org/10.2337/db18-0440
PubMed:View item in PubMed

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