Serum Osteocalcin Is Inversely Associated With Adipocyte-Specific Fatty Acid–Binding Protein in the Korean Metabolic Syndrome Research Initiatives

Recent studies (1) have reported that adipokines might act in a paracrine manner on osteoblasts and suppress osteoblast activity or differentiation—or both—in pathological conditions. Adipocyte-specific fatty acid–binding protein (A-FABP) is highly expressed in adipose tissue and may act systemically to regulate lipid and glucose metabolism (2). However, the association between serum osteocalcin with adipokines and A-FABP remains unclear in humans. Therefore, the aim of this study was to clarify the relationship between serum osteocalcin and the parameters of the metabolic syndrome and the association of serum osteocalcin with adipokines and A-FABP.

This was a cross-sectional study carried out by the Korean Metabolic Syndrome Research Initiative. The 124 obese subjects underwent a standardized examination at four university hospitals in Korea. The control group included 80 nonobese individuals. All subjects were free of medications such as sex steroids, corticosteroids, vitamin D, calcitonin, and bisphosphonates. Type 2 diabetes has been shown to alter the serum osteocalcin levels (3), therefore, the obese patients were divided into two groups based on the presence or absence of type 2 diabetes. Group 1 consisted of the control subjects (n = 80), group 2 had the obese subjects without diabetes (n = 74), and group 3 had the obese subjects with diabetes (n = 50). The levels of fasting plasma glucose, lipids, osteocalcin, and adipokines such as leptin, retinol-binding protein 4 (RBP4), and A-FABP were measured. All statistical analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC).

The patients affected by the metabolic syndrome, according to the NECP- ATP III guidelines, accounted for: in group 1, 30.4%; in group 2, 54.2%; and in group 3, 58.7%. After adjustment for age, sex, and menopausal status, group 3 showed significantly lower serum osteocalcin levels than groups 1 and 2 (6842.0 ± 454.6 pg/ml vs. 9204.7 ± 357.4 pg/ml vs. 8627.9 ± 376.6 pg/ml, respectively, P < 0.001). The serum osteocalcin levels showed a significant inverse correlation with the parameters of the metabolic syndrome such as BMI, waist circumference, blood pressure, and fasting glucose (P < 0.01) and A-FABP (P < 0.05). However, osteocalcin was not significantly correlated with triglycerides, HDL cholesterol, leptin, and RBP4. Adjustments for various confounding factors such as age, sex, menopausal status, BMI, and smoking status showed that the serum osteocalcin retained a significant inverse correlation with A-FABP (r = −0.152, P < 0.05).

The results of this study showed lower serum osteocalcin levels in the obese group with diabetes compared with the other groups. This reduction was likely due to the significant inverse association of the serum osteocalcin with BMI and fasting glucose level in the Korean subjects. The findings of this study are consistent with those of a recent study (3,4) that showed that obesity and type 2 diabetes were associated with significantly lower osteocalcin levels. In addition, a significant association between serum osteocalcin levels and A-FABP was observed for the first time. The data are limited by the fact that the patients' physical activity and diabetes medications were not taken into consideration. However, our findings may suggest additional approaches to the evaluation of cross-linking of bone, glucose, and fat metabolism.