Nephrin is produced in visceral adipose tissue in humans and associates with insulin resistance

Abstract

<p><strong>Aims: </strong>Nephrinuria and podocinuria have been proposed as early markers of podocytopathy. We explored whether nephrin and podocin are expressed in subcutaneous (SAT) and visceral adipose tissue (VAT), and report their determinants.</p><p><strong>Methods: </strong>Forty-one subjects with obesity (OS, age: 51 [41-57] yrs, M/F: 6/34) and twenty-nine lean controls (HC, age: 43 [35-51] yrs, M/F: 9/20) were studied. During metabolic bariatric surgery (MBS) VAT and SAT samples were collected. Only SAT samples were collected from HC. VAT samples from lean surgical patients served as an additional comparison group. Nephrin and podocin mRNA and protein expression were assessed in VAT/SAT, and nephrin and podocin levels were measured in plasma and urine.</p><p><strong>Results: </strong>Podocin was not expressed in SAT or VAT. Nephrin mRNA was detected in VAT but not SAT, and nephrin protein expression was higher in OS. In plasma, low levels of nephrin were detected, which were directly associated with insulin sensitivity. Urinary nephrin exhibited an inverse association with insulin sensitivity, which persisted two years after MBS.</p><p><strong>Conclusions: </strong>Nephrin is ectopically produced in VAT. Circulating and urinary nephrin show opposite associations with insulin sensitivity, compatible with early nephrin loss into the urine and compensatory regulation of VAT derived nephrin. These findings warrant further investigation.</p>