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

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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., Li, L., Wiegand, S., Brachs, M., Leupelt, V., Ernert, A., Kühnen, P., Hübner, N., Robinson, P., Chen, W., 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
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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