We identified soluble epidermal growth factor receptor (sEGFR), a hepatokine, and Adipsin, a adipokine, by serum quantitative proteomics as common factors, whose protein levels were significantly reduced across 4, 8, 12, and 24 weeks of ages in obese diabetic db/db mice and were restored by treatment with liraglutide. In this study, we investigated the properties of sEGFR and Adipsin as biomarkers in mouse and human. In mice, the expression of EGFR and Adipsin were abundant in the liver and adipose tissue, respectively, and significantly reduced in db/db mice. The sEGFR and Adipsin were significantly decreased in sera of high-fat diet-fed mice and ob/ob mice. Next, we measured the sEGFR and Adipsin levels in sera from 47 nondiabetes subjects and 106 patients with type 2 diabetes, and analyzed the correlation with clinical parameters by using multiple linear regression analysis. No correlations were observed between sEGFR and Adipsin levels. The sEGFR levels were positively correlated with HbA1c, fasting blood glucose, and HOMA-IR, and the association was remained after adjustment for age and sex (β = 0.357, p < 0.001; β = 0.299, p < 0.001; β = 0.259, p = 0.004). The sEGFR levels were also positively correlated with T-chol, TG, LDL-chol, and AST after adjustment for age and sex (β = 0.378, p < 0.001; β = 0.275, p < 0.001; β = 0.235, p = 0.004; β = 0.202, p = 0.014). The Adipsin levels were positively correlated with BMI, waist circumference, fasting serum insulin, and HOMA-IR, and remained correlation after adjustment for age and sex (β = 0.532, p < 0.001; β = 0.475, p < 0.001; β = 0.383, p < 0.001; β = 0.342, p = 0.003). The Adipsin levels were also positively correlated with FIB-4 index (liver fibrosis index), and negatively correlated with eGFR after adjustment for age and sex (β = 0.264, p = 0.013; β = -0.352, p < 0.001). These findings suggest that sEGFR and Adipsin are independent biomarkers that correlate with factors for insulin resistance, and might reflect liver and fat insulin resistance, respectively.
M. Kyohara: None. J. Shirakawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.
