Thrifty energy phenotype predicts weight regain in postmenopausal women with overweight or obesity and is related to FGFR1 signaling

Long term improvement of body weight and metabolism is highly requested in obesity. The specific impact of weight loss associated temporary negative energy balance or modified body composition on metabolism and weight regain is unclear. We randomly assigned 80 post-menopausal women (BMI 33.9 (32.2–36.8)kg/m2) to an intervention (IG) or control group (CG). IG underwent a dietary three month-weight loss intervention followed by a four week-weight maintenance period without negative energy balance. The CG was instructed to keep their weight stable. Phenotyping was performed at baseline (M0), after weight loss (M3), the maintenance period (M4) and 24-month follow-up (M24). Co-primary outcomes were changes of insulin sensitivity (ISIClamp) and lean body mass (LBM). Energy metabolism and adipose gene expression were secondary endpoints. Between March 2012 and July 2015, 479 subjects were screened for eligibility. 80 subjects were randomly assigned to IG (n = 40) or CG (n = 40). The total number of dropouts was 18 (IG: n = 13, CG: n = 5). LBM and ISIClamp were stable in the CG between M0 and M3, but were changed in the IG at M3 (LBM: −1.4 (95%CI -2.2-(-0.6)) kg and ISIClamp: +0.020 (95%CI 0.012–0.028) mg·kg−1·min−1/(mU·l−1)) (p