Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro

• Published in: International journal of molecular sciences 2020-10, Vol.21 (21), p.8168
• Main Authors: Schmid, Andreas, Gehl, Jonas, Thomalla, Miriam, Hochberg, Alexandra, Kreiß, Anja, Patz, Marissa, Karrasch, Thomas, Schäffler, Andreas
• Format: Article
• Language: English
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Adipokines - blood; Adipokines - genetics; Adipokines - metabolism; Adult; Animals; Bariatric Surgery - methods; Bile Acids and Salts - pharmacology; Cells, Cultured; Disease Models, Animal; Down-Regulation; Female; Gastrointestinal Agents - pharmacology; Glucagon-Like Peptide 1 - pharmacology; Humans; Incretins - pharmacology; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Obesity - blood; Obesity - metabolism; Obesity - pathology; Obesity - surgery; Tumor Necrosis Factors - blood; Tumor Necrosis Factors - genetics; Tumor Necrosis Factors - metabolism; Weight Loss
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms21218168

The adipokine CTRP-3 (C1q/TNF-related protein-3) exerts anti-inflammatory and anti-diabetic effects. Its regulation in obesity and during weight loss is unknown. Serum and adipose tissue (AT) samples were obtained from patients ( = 179) undergoing bariatric surgery (BS). Moreover, patients ( = 131) participating in a low-calorie diet (LCD) program were studied. CTRP 3 levels were quantified by ELISA and mRNA expression was analyzed in AT and in 3T3-L1 adipocytes treated with bile acids and incretins. There was a persistent downregulation of CTRP-3 serum levels during weight loss. CTRP-3 expression was higher in subcutaneous than in visceral AT and serum levels of CTRP-3 were positively related to AT expression levels. A rapid decrease of circulating CTRP-3 was observed immediately upon BS, suggesting weight loss-independent regulatory mechanisms. Adipocytes CTRP-3 expression was inhibited by primary bile acid species and GLP 1. Adipocyte-specific CTRP-3 deficiency increased bile acid receptor expression. Circulating CTRP-3 levels are downregulated during weight loss, with a considerable decline occurring immediately upon BS. Mechanisms dependent and independent of weight loss cause the post-surgical decline of CTRP-3. The data strongly argue for regulatory interrelations of CTRP-3 with bile acids and incretin system.