Maria Brachs1, Susanna Wiegand2, Verena Leupelt3, Andrea Ernert2, Ulrich Kintscher4, Reiner Jumpertz von Schwarzenberg1, Anne-Marie Decker1, Thomas Bobbert3, Norbert Hübner5, Wei Chen5, Heiko Krude2, Joachim Spranger1, Knut Mai6. 1. Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Experimental and Clinical Research Center (ECRC), Berlin, Germany. 2. Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin, Berlin, Germany. 3. Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany. 4. Charité-Center for Cardiovascular Research (CCR), Berlin, Germany. 5. Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, 13125, Berlin, Germany. 6. Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Experimental and Clinical Research Center (ECRC), Berlin, Germany. Electronic address: knut.mai@charite.de.
Abstract
INTRODUCTION: In weight loss trials, a considerable inter-individual variability in reduction of fat mass and changes of insulin resistance is observed, even under standardized study conditions. The underlying mechanisms are not well understood. Given the metabolic properties of the atrial natriuretic peptide (ANP) system, we hypothesized that ANP signaling might be involved in this phenomenon by changes of ANP secretion or receptor balance. Therefore, we investigated the impact of systemic, adipose and myocellular ANP system on metabolic and anthropometric improvements during weight loss. METHODS: We comprehensively investigated 143 subjects (31 male, 112 female) before and after a 3 month-standardized weight loss program. The time course of BMI, fat mass, insulin sensitivity, circulating mid-regional proANP (MR-proANP) levels as well as adipose and myocellular natriuretic receptor A (NPR-A) and C (NPR-C) mRNA expression were investigated. RESULTS:BMI decreased by -12.6±3.7%. This was accompanied by a remarkable decrease of adipose NPR-C expression (1005.0±488.4 vs. 556.7±465.6; p<0.001) as well as a tendency towards increased adipose NPR-A expression (4644.7±946.8 vs. 4877.6±869.8; p=0.051). Weight loss induced changes in NPR-C (ΔNPR-C) was linked to relative reduction of total fat mass (ΔFM) (r=0.281; p<0.05), reduction of BMI (r=0.277; p<0.01), and increase of free fatty acids (ΔFFA) (r=-0.258; p<0.05). Basal NPR-C expression and weight loss induced ΔNPR-C independently explained 22.7% of ΔFM. In addition, ΔMR-proANP was independently associated with improvement of insulin sensitivity (standardized ß=0.246, p<0.01). DISCUSSION: ANP receptor expression predicted the degree of weight loss induced fat mass reduction. Our comprehensive human data support that peripheral ANP signalling is involved in control of adipose tissue plasticity and function during weight loss. (Funded by the Deutsche Forschungsgemeinschaft (KFO281/2), the Berlin Institute of Health (BIH) and the German Centre for Cardiovascular Research (DZHK/BMBF); ClinicalTrials.gov number: NCT00850629).
RCT Entities:
INTRODUCTION: In weight loss trials, a considerable inter-individual variability in reduction of fat mass and changes of insulin resistance is observed, even under standardized study conditions. The underlying mechanisms are not well understood. Given the metabolic properties of the atrial natriuretic peptide (ANP) system, we hypothesized that ANP signaling might be involved in this phenomenon by changes of ANP secretion or receptor balance. Therefore, we investigated the impact of systemic, adipose and myocellular ANP system on metabolic and anthropometric improvements during weight loss. METHODS: We comprehensively investigated 143 subjects (31 male, 112 female) before and after a 3 month-standardized weight loss program. The time course of BMI, fat mass, insulin sensitivity, circulating mid-regional proANP (MR-proANP) levels as well as adipose and myocellular natriuretic receptor A (NPR-A) and C (NPR-C) mRNA expression were investigated. RESULTS: BMI decreased by -12.6±3.7%. This was accompanied by a remarkable decrease of adipose NPR-C expression (1005.0±488.4 vs. 556.7±465.6; p<0.001) as well as a tendency towards increased adipose NPR-A expression (4644.7±946.8 vs. 4877.6±869.8; p=0.051). Weight loss induced changes in NPR-C (ΔNPR-C) was linked to relative reduction of total fat mass (ΔFM) (r=0.281; p<0.05), reduction of BMI (r=0.277; p<0.01), and increase of free fatty acids (ΔFFA) (r=-0.258; p<0.05). Basal NPR-C expression and weight loss induced ΔNPR-C independently explained 22.7% of ΔFM. In addition, ΔMR-proANP was independently associated with improvement of insulin sensitivity (standardized ß=0.246, p<0.01). DISCUSSION: ANP receptor expression predicted the degree of weight loss induced fat mass reduction. Our comprehensive human data support that peripheral ANP signalling is involved in control of adipose tissue plasticity and function during weight loss. (Funded by the Deutsche Forschungsgemeinschaft (KFO281/2), the Berlin Institute of Health (BIH) and the German Centre for Cardiovascular Research (DZHK/BMBF); ClinicalTrials.gov number: NCT00850629).
Authors: Linna Li; Leonard Spranger; Dominik Soll; Finja Beer; Maria Brachs; Joachim Spranger; Knut Mai Journal: Metabolism Date: 2020-10-13 Impact factor: 8.694
Authors: Linna Li; Leonard Spranger; Nicole Stobäus; Finja Beer; Anne-Marie Decker; Charlotte Wernicke; Sebastian Brachs; Maria Brachs; Joachim Spranger; Knut Mai Journal: Nutr Diabetes Date: 2021-10-05 Impact factor: 5.097