title: ANP system activity predicts variability of fat mass reduction and insulin sensitivity during weight loss.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Brachs
authors.affiliation: Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Wiegand
authors.affiliation: Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Leupelt
authors.affiliation: Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ernert
authors.affiliation: Charité-Center for Cardiovascular Research (CCR), Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kintscher
authors.affiliation: Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Jumpertz von Schwarzenberg
authors.affiliation: Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Decker
authors.affiliation: Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bobbert
authors.affiliation: Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, 13125, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hübner
authors.affiliation: Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, 13125, Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
authors.affiliation: Department of Endocrinology & Metabolism, Charite - Universitätsmedizin, Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.affiliation: 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.
authors.forename: Knut
authors.initials: K
authors.lastname: Mai
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D050154:Adiposity / Q000502:physiology*; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001786:Blood Glucose; D015992:Body Mass Index; D031204:Caloric Restriction; D003376:Counseling; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000378:metabolism / Q000628:therapy; D050177:Overweight / Q000178:diet therapy / Q000378:metabolism / Q000628:therapy*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015431:Weight Loss / Q000502:physiology*; D061217:Weight Reduction Programs
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor
keywords: ANP system; Fat mass; Insulin sensitivity; Weight loss