An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-Term Body Weight Maintenance
abstract
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Access this abstract nowLifestyle-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 lifestyle-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 [< or ≥3% weight regain] variable) 18 months after intended weight loss in the entire cohort. Key results were confirmed in a similar randomized controlled trial 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.
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An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-Term Body Weight Maintenance
Diabetes 2019 Jan 01;68(1)57-65, K Mai, L Li, S Wiegand, M Brachs, V Leupelt, A Ernert, P Kühnen, N Hübner, P Robinson, W Chen, H Krude, J SprangerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.