CDH13 abundance interferes with adipocyte differentiation and is a novel biomarker for adipose tissue health.

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.