Simon Göddeke1,2,3, Birgit Knebel1,3, Pia Fahlbusch1,2,3, Tina Hörbelt1,2,3, Gereon Poschmann4, Frederique van de Velde5, Tim Benninghoff1,2,3, Hadi Al-Hasani1,2,3, Sylvia Jacob1,3, Yves Van Nieuwenhove6, Bruno Lapauw5, Stefan Lehr1,3, D Margriet Ouwens1,3,5, Jorg Kotzka7,8. 1. Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Duesseldorf, Leibniz Center for Diabetes Research, Aufm Hennekamp 65, 40225, Duesseldorf, Germany. 2. Institute of Clinical Biochemistry and Pathobiochemistry, Medical Faculty, German Diabetes Center at the Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany. 3. German Center of Diabetes Research Partner, Duesseldorf, Germany. 4. Molecular Proteomics Laboratory, Biomedizinisches Forschungszentrum (BMFZ), Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany. 5. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium. 6. Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium. 7. Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Duesseldorf, Leibniz Center for Diabetes Research, Aufm Hennekamp 65, 40225, Duesseldorf, Germany. joerg.kotzka@ddz.uni-duesseldorf.de. 8. German Center of Diabetes Research Partner, Duesseldorf, Germany. joerg.kotzka@ddz.uni-duesseldorf.de.
Abstract
BACKGROUND: CDH13, an atypical member of the cadherin superfamily, has been identified in adipocyte secretomes of lean mouse models. CDH13 abundance differs in mouse models according to their susceptibility to develop metabolic disorders, but the role of CDH13 in adipose tissue is unknown. METHODS: Secreted CDH13 protein levels and mRNA levels in visceral adipose tissue were determined in lean and obese mouse models. In vitro studies were performed in 3T3-L1 adipocytes to determine the role of CDH13 in adipocyte differentiation. The pathophysiological impact of visceral adipose tissue CDH13 mRNA and circulating CDH13 levels were determined in humans (normal-weight men n = 37, obese men n = 109 including n = 51 type 2 diabetes patients) and in obese patients (n = 14) pre- and post-metabolic surgery. RESULTS: This study shows that in visceral adipose tissue CDH13 protein secretion and mRNA levels were decreased in obese mouse models. Mechanistically, CDH13 affects lipid metabolism during adipogenesis but not in mature adipocytes. CDH13 knockdown during adipogenesis reduced fatty acid uptake and lipid content in developing adipocytes. Furthermore, CDH13 depletion during adipogenesis lowered the induction of PPARγ and C/EBPα expression. These observations are of pathophysiological impact since visceral adipose tissue CDH13 mRNA and circulating CDH13 levels were decreased in obese men compared to normal-weight controls. Weight loss induced by bariatric surgery restored circulating CDH13 to levels found in normal-weight controls. CONCLUSIONS: CDH13 levels in adipose tissue and the circulation are affected by obesity in mouse models and humans and are restored by weight loss in humans. CDH13 interferes with the differentiation potential of adipocytes and therefore is a marker for plasticity of fat tissue that might reflect the health status of adipose tissue.
BACKGROUND:CDH13, an atypical member of the cadherin superfamily, has been identified in adipocyte secretomes of lean mouse models. CDH13 abundance differs in mouse models according to their susceptibility to develop metabolic disorders, but the role of CDH13 in adipose tissue is unknown. METHODS: Secreted CDH13 protein levels and mRNA levels in visceral adipose tissue were determined in lean and obesemouse models. In vitro studies were performed in 3T3-L1 adipocytes to determine the role of CDH13 in adipocyte differentiation. The pathophysiological impact of visceral adipose tissue CDH13 mRNA and circulating CDH13 levels were determined in humans (normal-weight men n = 37, obesemen n = 109 including n = 51 type 2 diabetespatients) and in obesepatients (n = 14) pre- and post-metabolic surgery. RESULTS: This study shows that in visceral adipose tissue CDH13 protein secretion and mRNA levels were decreased in obesemouse models. Mechanistically, CDH13 affects lipid metabolism during adipogenesis but not in mature adipocytes. CDH13 knockdown during adipogenesis reduced fatty acid uptake and lipid content in developing adipocytes. Furthermore, CDH13 depletion during adipogenesis lowered the induction of PPARγ and C/EBPα expression. These observations are of pathophysiological impact since visceral adipose tissue CDH13 mRNA and circulating CDH13 levels were decreased in obesemen compared to normal-weight controls. Weight loss induced by bariatric surgery restored circulating CDH13 to levels found in normal-weight controls. CONCLUSIONS:CDH13 levels in adipose tissue and the circulation are affected by obesity in mouse models and humans and are restored by weight loss in humans. CDH13 interferes with the differentiation potential of adipocytes and therefore is a marker for plasticity of fat tissue that might reflect the health status of adipose tissue.
Authors: Sergio E Palma-Vera; Henry Reyer; Martina Langhammer; Norbert Reinsch; Lorena Derezanin; Joerns Fickel; Saber Qanbari; Joachim M Weitzel; Soeren Franzenburg; Georg Hemmrich-Stanisak; Jennifer Schoen Journal: BMC Biol Date: 2022-02-21 Impact factor: 7.364
Authors: Cassandra N Spracklen; Apoorva K Iyengar; Swarooparani Vadlamudi; Chelsea K Raulerson; Anne U Jackson; Sarah M Brotman; Ying Wu; Maren E Cannon; James P Davis; Aaron T Crain; Kevin W Currin; Hannah J Perrin; Narisu Narisu; Heather M Stringham; Christian Fuchsberger; Adam E Locke; Ryan P Welch; Johanna K Kuusisto; Päivi Pajukanta; Laura J Scott; Yun Li; Francis S Collins; Michael Boehnke; Markku Laakso; Karen L Mohlke Journal: PLoS Genet Date: 2020-09-11 Impact factor: 5.917