The protective effect of human renal sinus fat on glomerular cells is reversed by the hepatokine fetuin-A

• Published in: Scientific reports Vol. 7; no. 1; pp. 2261 - 12
• Main Authors: Wagner, R., Machann, J., Guthoff, M., Nawroth, P. P., Nadalin, S., Saleem, M. A., Heyne, N., Königsrainer, A., Fend, F., Schick, F., Fritsche, A., Stefan, N., Häring, H.-U., Schleicher, E., Siegel-Axel, D. I.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 101/1; 13; 13/106; 13/21; 13/31; 14; 38; 631/80/304; 692/4022/1585/2759; 82; 82/79; 96; 96/63; Adipocytes; Adipocytes - metabolism; Adult; alpha-2-HS-Glycoprotein - metabolism; Cells, Cultured; Coculture Techniques; Creatinine; Cytokines - metabolism; Diabetes mellitus; Endothelial cells; Epidermal growth factor receptors; Fatty liver; Female; Gene Expression; Glomerular filtration rate; Humanities and Social Sciences; Humans; Immunohistochemistry; Inflammation Mediators - metabolism; Intra-Abdominal Fat - diagnostic imaging; Intra-Abdominal Fat - physiology; Kidney - anatomy & histology; Kidney - diagnostic imaging; Kidney - physiology; Kidney Glomerulus - cytology; Kidney Glomerulus - metabolism; Liver; Liver diseases; Macrophages - metabolism; Magnetic resonance imaging; Magnetic resonance spectroscopy; Male; Middle Aged; multidisciplinary; Renal artery; Renal Artery - anatomy & histology; Renal Artery - diagnostic imaging; Renal function; RNA, Messenger - genetics; Science; Science (multidisciplinary); Sinus; Sinuses; Spectroscopy
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02210-4

Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC. However, fetuin-A inverted these benign effects of RSFC from an anti- to a proinflammatory status. RSF was quantified by magnetic resonance imaging and liver fat content by 1 H-MR spectroscopy in 449 individuals at risk for type 2 diabetes. Impaired renal function was determined via urinary albumin/creatinine-ratio (uACR). RSF did not correlate with uACR in subjects without NAFLD (n = 212, p = 0.94), but correlated positively in subjects with NAFLD (n = 105, p = 0.0005). Estimated glomerular filtration rate (eGRF) was inversely correlated with RSF, suggesting lower eGFR for subjects with higher RSF (r = 0.24, p < 0.0001). In conclusion, our data suggest that in the presence of NAFLD elevated fetuin-A levels may impair renal function by RSF-induced proinflammatory signalling in glomerular cells.