Abstract
PurposeSecreted frizzled-related protein 5 (SFRP5) is an adipokine, which acts as an inhibitor of noncanonical WNT signaling pathway. It has been suggested to exert anti-inflammatory and insulin-sensitizing effects, however, contradictory data has also been reported. The aim of this study was to assess serum SFRP5 concentration in a young healthy population in relation to insulin sensitivity and its regulation by hyperinsulinemia and/or serum free fatty acids (FFA) elevation.MethodsWe examined 150 healthy subjects (83 normal-weight and 67 overweight/obese). Insulin sensitivity (M) was measured with hyperinsulinemic-euglycemic clamp. In 20 male subjects, clamp was prolonged to 6 h and after 1 week another clamp with the concurrent Intralipid/heparin infusion was performed. Independent group of 10 male subjects received infusions of Intralipid/heparin or saline in 1-week interval.ResultsBaseline SFRP5 was lower in the overweight/obese group (p = 0.01) and was positively associated with M (r = 0.23, p = 0.006) and serum adiponectin (r = 0.55, p < 0.001) and negatively with BMI (r = −0.18, p = 0.03). In multiple regression analysis, adiponectin was independently associated with SFRP5. Insulin infusion resulted in a decrease in serum SFRP5, both at 120′ (p = 0.02) and 360′ (p = 0.031). This effect was not observed during the clamp with Intralipid/heparin as well as during Intralipid/heparin alone or saline infusions.ConclusionsThe relation between SFRP5 and insulin sensitivity is mainly dependent on adiponectin. FFA abolish a decrease in circulating SFRP5 caused by insulin, but Intralipid/heparin infusion alone does not regulate SFRP5 concentration. Insulin seems to be more important factor in the regulation of circulating SFRP5 levels than FFA.
Highlights
The worldwide epidemic of overweight and obesity is expanding and has become an alarming problem as well as major health challenge [1]
We investigated the relationship of circulating Secreted frizzled-related protein 5 (SFRP5) levels with various clinical and biochemical parameters by using partial correlations (Table 2)
Serum SFRP5 positively associated with insulin sensitivity (r = 0.23, p = 0.006), HDL-cholesterol (r = 0.25, p = 0.003) and negatively with BMI (r = −0.18, p = 0.03) waist
Summary
The worldwide epidemic of overweight and obesity is expanding and has become an alarming problem as well as major health challenge [1]. The Wingless-type mouse mammary tumor virus integration site (WNT) family of secreted glycoproteins has established roles in cell differentiation and function in several tissues including WAT [3]. One study showed that in human adipocytes, SFRP5 impairs insulin sensitivity [8], whereas associations between blood concentration of SFRP5 and homoeostasis model assessment of insulin resistance (HOMA-IR) vary between studies [4, 9]. Some studies showed that circulating SFRP5 concentrations were elevated or decreased in obese and T2D patients [11, 12]. These contradictions implied that the functions of SFRP5 in the pathogenesis of T2D and obesity still are little known
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