Bone-derived osteocalcin has been suggested to be a metabolic regulator, potentially improving insulin sensitivity. To scrutinize the relation between osteocalcin and peripheral insulin sensitivity, I analyzed changes of 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). 74 nonsmoking men (45–55 yr) with MetS were randomized to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control group. Before and after the 6 months intervention period clinical and laboratory parameters and serum osteocalcin levels were determined in fasting blood samples. Lifestyle-induced changes of body composition were analyzed by Dual Energy X Ray-Absorptiometry (DXA). 30 participants in the control and 33 participants in the intervention group completed the study and were included in the data analysis. In participants of the intervention group, weight loss resulted in markedly improved insulin sensitivity and amelioration of low-grade 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 associated with changes in CRP but not with changes in insulin concentration, adipose tissue mass or bone mineral density. These results illustrate that the weight loss-induced higher serum osteocalcin is primarily associated with reduced inflammation.:List of abbreviations ................................................................................................................................ 4
Short summary ........................................................................................................................................ 5
Graphical abstract ................................................................................................................................... 6
2 Introduction ......................................................................................................................................... 7
2a The metabolic syndrome ............................................................................................................... 8
2b C-reactive protein (CRP) and its role in MetS .............................................................................. 12
2c Bone-derived osteocalcin and inflammation ............................................................................... 14
2d Study design ................................................................................................................................. 17
3 Original peer-reviewed publication: “Osteocalcin Is Independently Associated with C-Reactive Protein during Lifestyle-Induced Weight Loss in Metabolic Syndrome” .............................................. 19
4 Summary ............................................................................................................................................ 32
5 References ......................................................................................................................................... 36
6 Supplementary data ........................................................................................................................... 45
7 Declaration about the independent preparation of the work ........................................................... 48
8 Presentation of own contribution ..................................................................................................... 49
9 Curriculum vitae ................................................................................................................................. 51
10 Publications ...................................................................................................................................... 57
11 Acknowledgments ............................................................................................................................ 5
