Thrifty energy phenotype predicts weight regain in postmenopausal women with overweight or obesity and is related to FGFR1 signaling. Issue 4 (April 2023)

• Record Type: Journal Article
• Authors: Spranger, Leonard; Weiner, January; Bredow, Josephine; Zeitz, Ulrike; Grittner, Ulrike; Boschmann, Michael; Dickmann, Sophia; Stobäus, Nicole; Schwartzenberg, Reiner Jumpertz-von; Brachs, Maria; Spranger, Joachim; Mai, Knut
• Is Part Of: Clinical nutrition. Volume 42:Issue 4(2023)
• Page Start: 559
• Page End: 567
• Publication Date: 2023-04
• Subjects: Insulin resistance -- Weight loss -- Energy restriction -- Energy metabolism -- Fat mass -- Weight loss maintenance -- Weight regain; Critically ill -- Nutrition -- Periodicals; Diet therapy -- Periodicals; Parenteral feeding -- Periodicals; Enteral feeding -- Periodicals; Enteral Nutrition -- Periodicals; Parenteral Nutrition -- Periodicals; Metabolism -- Periodicals; Diétothérapie -- Périodiques; Alimentation parentérale -- Périodiques; Alimentation entérale -- Périodiques; Nutrition -- Périodiques; Diet therapy; Enteral feeding; Nutrition; Parenteral feeding; Electronic journals; Periodicals; Electronic journals; 615.854
• DOI: 10.1016/j.clnu.2023.02.020
• Languages: English
• ISSNs: 0261-5614

Abstract

Summary: Background&aims: 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. Methods: We randomly assigned 80 post-menopausal women (BMI 33.9 (32.2–36.8)kg/m 2 ) 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. Results: 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 < 0.01 and p < 0.05 for IG vs. CG, respectively). Effects on LBM, ISIClamp, FM and BMI were preserved until M4. Lower resting energy expenditure per LBM (REELBM ) at M3 and stronger difference of REELBM between M3 and M4 (ΔREELBM-M3M4 ), which indicates a thrifty phenotype, were positively associated with FM regain at M24 (p = 0.022 and p = 0.044, respectively). Gene set enrichment analysis revealed a relationship of this phenotype to weight loss-induced adaption of adipose FGFR1 signaling. Conclusion: Negative energy balance had no additional effect on insulin sensitivity. FGFR1 signaling might be involved in the adaption of energy expenditure to temporary negative energy balance, which indicates a thrifty phenotype susceptible to weight regain. Trial registration: ClinicalTrials.gov number: NCT01105143, https://clinicaltrials.gov/ct2/show/NCT01105143, date of registration: April 16th, 2010