Osteocalcin Is Independently Associated with C-Reactive Protein during Lifestyle-Induced Weight Loss in Metabolic Syndrome.

Silke Zimmermann,Maria Beatriz Walter Costa,Jochen G Schneider,Ronald Biemann,Akash Mathew,Berend Isermann,Shruthi Krishnan,Kirsten Roomp

doi:10.3390/metabo11080526

Abstract

Bone-derived osteocalcin has been suggested to be a metabolic regulator. To scrutinize the relation between osteocalcin and peripheral insulin sensitivity, we analyzed changes in serum osteocalcin relative to changes in insulin sensitivity, low-grade inflammation, and bone mineral density following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). Participants with MetS were randomized to a weight loss program or to a control group. Before and after the 6-month intervention period, clinical and laboratory parameters and serum osteocalcin levels were determined. Changes in body composition were analyzed by dual-energy X-ray absorptiometry (DXA). In participants of the intervention group, weight loss resulted in improved insulin sensitivity and amelioration of inflammation. Increased serum levels of osteocalcin correlated inversely with BMI (r = −0.63; p < 0.001), total fat mass (r = −0.58, p < 0.001), total lean mass (r = −0.45, p < 0.001), C-reactive protein (CRP) (r = −0.37; p < 0.01), insulin (r = −0.4; p < 0.001), leptin (r = −0.53; p < 0.001), triglycerides (r = −0.42; p < 0.001), and alanine aminotransferase (ALAT) (r = −0.52; p < 0.001). Regression analysis revealed that osteocalcin was independently associated with changes in CRP but not with changes in insulin concentration, fat mass, or bone mineral density, suggesting that weight loss-induced higher serum osteocalcin is primarily associated with reduced inflammation.

Highlights

The cluster of raised fasting plasma glucose, abdominal obesity, high triglycerides, and high blood pressure—all well-established cardiovascular risk factors—is commonly referred to as metabolic syndrome (MetS)
Clinical and laboratory parameters and osteocalcin concentrations were determined in fasting blood samples before and after the six-month weight loss intervention (Figure 1, Supplementary Table S1)
To address the question of whether weight loss affects osteocalcin levels in individuals with MetS, and whether osteocalcin is associated with metabolic parameters, body composition, or inflammation, we determined the changes and interrelations of predefined parameters before and after lifestyle-induced weight loss (Figure 3, Supplementary Table S1)

Summary

Introduction

The cluster of raised fasting plasma glucose, abdominal obesity, high triglycerides, and high blood pressure—all well-established cardiovascular risk factors—is commonly referred to as metabolic syndrome (MetS). In MetS, lifestyle-induced weight loss is regarded an effective therapy to reverse insulin resistance, to prevent T2DM, and to reduce low-grade inflammation and CVD [2,3]. Of the different bone turnover markers, reduced osteocalcin levels are associated with overweight and MetS parameters that include higher waist circumference, higher triglyceride and glucose levels, increased blood pressure, and lower HDL-cholesterol [7,8,9]. The relationship between changes in osteocalcin, body composition, metabolic parameters, and systemic low-grade inflammation following lifestyle-induced weight loss in MetS remains unknown. To address this question, we determined the changes and interrelations of osteocalcin with clinical, metabolic, and inflammatory parameters following lifestyle-induced weight loss in 74 well-defined individuals with MetS in a prospective study

Clinical and Laboratory Parameters

Research Design

Dual Energy X-ray Absorptiometry

Statistical Analysis