Abstract
Background: Emerging evidence indicates that ectopic skeletal muscle adiposity (i.e., myosteatosis) is greater in African than in European ancestry individuals, and may be a novel risk factor contributing to increased diabetes risk. However, the biological mechanisms underlying myosteatosis are largely unknown. In vitro studies suggest that a Wnt pathway inhibitor, Dickkopf related protein 1 (DKK1), could be a novel biomarker with a role in adiposity regulation. Methods: We measured fasting serum DKK1 in a pilot study of 159 elderly Afro-Caribbean men (mean age 63.4 years, mean BMI 27.8 kg/m2), a random subset of a population-based study comprising ∼3000 African Ancestry men with fasting morning blood collections for biomarker analyses. DKK1 was measured in duplicate in previously unthawed serum with ELISA.Also assessed were anthropometrics, DXA measured adiposity, and lower leg CT measured myosteatosis (intermuscular adiposity (mm2)) and skeletal muscle density (which reflects the intra-muscular fat content ((mg/cm3) such that greater intra-muscular adiposity reflects lower muscle density). Results: In Spearman correlation analysis DKK1 was positively associated with BMI (R=0.19, p=0.01), waist circumference (R=0.15, p=0.05), DXA total body fat (R=0.22, p=0.004), and DXA trunk fat (R=0.19, p=0.01), independent of age. In addition, DKK1 was associated positively with intermuscular fat (R=0.19, p=0.01), and inversely with muscle density (R=-0.29, p=<0.001), independent of age and BMI. No significant association was found between DKK1 and fasting serum glucose and insulin levels, and HOMA-IR. Conclusion: Our findings suggest for the first time that lower serum levels of DKK1 may be associated with greater overall adiposity, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of body fat among African ancestry and other population groups with a high risk of developing obesity and related metabolic disorders. Disclosure H. Ali: None. J.M. Zmuda: None. R. Cvejkus: None. E.E. Kershaw: Consultant; Self; Regeneron Pharmaceuticals, Inc.. A.L. Kuipers: None. C.H. Bunker: None. I. Miljkovic: None.
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