Cardiac natriuretic peptides (NP) are involved in cardio-renal regulation but also in lipolysis and lipid metabolism. The signaling receptor NPRA and the clearance receptor NPRC mediate the response to NP that is largely dependent on the ratio between the two receptors. Lipolysis increases when NPRC is selectively downregulated by starving or very-low calorie diet. Insulin is an anti-lipolytic hormone and also induces sodium-retention, suggesting a possible functional link with NP. Therefore we examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association between NP receptors expression in visceral adipose tissue (VAT) and insulin, HOMA index and metabolic profiles in patients undergoing renal surgery.Design and method:
Differentiated human adipocytes from VAT and SGBS cell line were treated with insulin in the presence of glucose. Further experiments in low-glucose media were performed to simulate in vivo starving conditions and to study glucose-insulin mediated genes involved in lipogenesis. Lipolysis was assessed by glycerol release assay. Fasting blood samples and VAT samples were taken from patients in the day of renal surgery.Results:
We observed a potent insulin-mediated and glucose-dependent up-regulation of NPRC, through the PI3K pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium hampered the insulin effect, likely through the modulation of glucose flux genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, higher HOMA index and higher total, LDL, and non-HDL cholesterol.Conclusions:
Insulin and glucose-dependent NPRC induction in adipocytes, especially in the contest of insulin resistance and increased insulin levels, might be a key factor linking hyperinsulinemia, metabolic syndrome and higher blood pressure.