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

Leonard Spranger, January Weiner, Josephine Bredow, Ulrike Zeitz, Ulrike Grittner, Michael Boschmann, Sophia Dickmann, Nicole Stobäus, Reiner Jumpertz-von Schwartzenberg, Maria Brachs, Joachim Spranger, Knut Mai

Journal: Clinical nutrition (Edinburgh, Scotland) 2023;42(4):559-567

PMID: 36863292

Full Text on Elsevier Science View on PubMed

Abstract

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) 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 (ISI) 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 ISI 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 ISI: +0.020 (95%CI 0.012-0.028) mg·kg·min/(mU·l)) (p < 0.01 and p < 0.05 for IG vs. CG, respectively). Effects on LBM, ISI, FM and BMI were preserved until M4. Lower resting energy expenditure per LBM (REE) at M3 and stronger difference of REE between M3 and M4 (ΔREE), 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.

Address: Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Insitute of Health, 10117, Berlin, Germany.; Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics Berlin, 10178, Germany.; Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178, Berlin, Germany.; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178, Berlin, Germany; Experimental and Clinical Research Center (ECRC) - Charité - Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany.; Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Insitute of Health, 10117, Berlin, Germany; Charité Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, 10117, Berlin, Germany.; Clinical Research Unit, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117, Berlin, Germany.; Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Insitute of Health, 10117, Berlin, Germany; Charité Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, 10117, Berlin, Germany; Treamid Therapeutics GmbH, Muellerstr. 178, 13353, Berlin, Germany.; Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Insitute of Health, 10117, Berlin, Germany; Charité Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, 10117, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany.; Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Insitute of Health, 10117, Berlin, Germany; Charité Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, 10117, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany. Electronic address: [email protected].

DOI: 10.1016/j.clnu.2023.02.020

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MeSH Terms: Female, Humans, Overweight, Insulin Resistance, Postmenopause, Obesity, Body Composition, Energy Metabolism, Weight Gain, Weight Loss, Receptor, Fibroblast Growth Factor, Type 1