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


  • K. Mai
  • L. Li
  • S. Wiegand
  • M. Brachs
  • V. Leupelt
  • A. Ernert
  • P. Kühnen
  • N. Hübner
  • P. Robinson
  • W. Chen
  • H. Krude
  • J. Spranger


  • Diabetes


  • Diabetes 68 (1): 57-65


  • 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.