ANP system activity predicts variability of fat mass reduction and insulin sensitivity during weight loss

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• 作者：Maria Brachs^a ; ^b ; ^c ; Susanna Wiegand^d ; Verena Leupelt^a ; ^b ; Andrea Ernert^d ; Ulrich Kintscher^b ; Reiner Jumpertz von Schwarzenberg^a ; ^b ; ^c ; Anne-Marie Decker^a ; ^b ; ^c ; Thomas Bobbert^a ; ^b ; Norbert H&uuml ; bner^e ; Wei Chen^e ; Heiko Krude^d ; Joachim Spranger^a ; ^b ; ^c ; Knut Mai^a ; ^b ; ^c ; ^{knut.mai@charite.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ANP ; atrial natriuretic peptide ; MR-proANP ; mid-regional proANP ; MR-proANPAUC ; area under the curve of MR-proANP during oral glucose load ; NPR-A ; natriuretic receptor A ; NPR-C ; natriuretic receptor C ; UCP3 ; uncoupling protein-3 ; ANT1 ; ATP/ADP translocase 1 ; BMI ; body mass index ; FM ; total fat mass ; FFA ; free fatty acid ; HOMA-IR ; homeostasis model assessment-estimated insulin resistance index ; ISIClamp ; insulin sensitivity index ; ΔNPR-C ; weight loss induced change of NPR-C ; ΔNPR-A ; weight loss in
• 刊名：Metabolism
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：65
• 期：6
• 页码：935-943
• 全文大小：600 K

文摘

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); f" data-locatorType="url" data-locatorKey="http://ClinicalTrials.gov">ClinicalTrials.gov number: NCT00850629).