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Horm Metab Res 2015; 47(02): 152-157
DOI: 10.1055/s-0034-1384521
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Roles of Circulating WNT-Signaling Proteins and WNT-Inhibitors in Human Adiposity, Insulin Resistance, Insulin Secretion, and Inflammation

R. U. Almario
1   Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, The University of California at Davis, Davis, CA, USA
,
S. E. Karakas
1   Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, The University of California at Davis, Davis, CA, USA
2   Department of Veterans Affairs Northern California Health Care System, Mather, CA, USA
› Author Affiliations
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Publication History

received 17 March 2014

accepted 16 June 2014

Publication Date:
04 August 2014 (online)

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Abstract

Wingless-type MMTV integration site family member (WNT) signaling and WNT-inhibitors have been implicated in regulation of adipogenesis, insulin resistance, pancreatic function, and inflammation. Our goal was to determine serum proteins involved in WNT signaling (WNT5 and WISP2) and WNT inhibition (SFRP4 and SFRP5) as they relate to obesity, serum adipokines, insulin resistance, insulin secretion, and inflammation in humans. Study population comprised 57 insulin resistant women with polycystic ovary syndrome (PCOS) and 27 reference women. In a cross-sectional study, blood samples were obtained at fasting, during oral, and frequently sampled intravenous glucose tolerance tests. Serum WNT5, WISP2, and SFRP4 concentrations did not differ between PCOS vs. reference women. Serum WNT5 correlated inversely with weight both in PCOS and reference women, and correlated directly with insulin response during oral glucose tolerance test in PCOS women. Serum WISP2 correlated directly with fatty acid binding protein 4. Serum SFRP5 did not differ between obese (n=32) vs. nonobese (n=25) PCOS women, but reference women had lower SFRP5 (p<5×10−6 as compared to both PCOS groups). Serum SFRP5 correlated inversely with IL-1β, TNF-α, cholesterol, and apoprotein B. These findings demonstrated that WNT5 correlated inversely with adiposity and directly with insulin response, and the WNT-inhibitor SFRP5 may be anti-inflammatory. Better understanding of the role of WNT signaling in obesity, insulin resistance, insulin secretion, lipoprotein metabolism, and inflammation is important for prevention and treatment of metabolic syndrome, diabetes and cardiovascular disease.

Key words

WNT5 - WISP2 - SFRP4 - SFRP5 - PCOS - obesity - insulin resistance
 

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