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

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.

SUBMITTER: Zimmermann S

PROVIDER: S-EPMC8400285 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceGenome-wide association studies have identified genetic loci influencing obesity risk in children. However, the importance of these loci in the associations with weight reduction through lifestyle interventions has not been investigated in large intervention trials.ObjectiveTo evaluate the associations between various obesity susceptibility loci and changes in body weight in children during an in-hospital, lifestyle intervention program.Design, setting, and participantsLong-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children (LOGIC), an interventional prospective cohort study, enrolled 1429 children with overweight or obesity to participate in an in-hospital lifestyle intervention program. Genotyping of 56 validated obesity single-nucleotide variants (SNVs) was performed, and the associations between the SNVs and body weight reduction during the intervention were evaluated using linear mixed-effects models for each SNV. The LOGIC study was conducted from January 6, 2006, to October 19, 2013; data analysis was performed from July 15, 2015, to November 6, 2016.ExposuresA 4- to 6-week standardized in-hospital lifestyle intervention program (daily physical activity, calorie-restricted diet, and behavioral therapy).Main outcomes and measuresThe association between 56 obesity-relevant SNVs and changes in body weight and body mass index.ResultsOf 1429 individuals enrolled in the LOGIC Study, 1198 individuals (mean [SD] age, 14.0 [2.2] years; 670 [56%] girls) were genotyped. A mean (SD) decrease was noted in body weight of -8.7 (3.6) kg (95% CI, -15.7 to -1.8 kg), and body mass index (calculated as weight in kilograms divided by height in meters squared) decreased by -3.3 (1.1) (95% CI, -5.4 to -1.1) (both P < .05). Five of 56 obesity SNVs were statistically significantly associated with a reduction of body weight or body mass index (all P < 8.93 × 10-4 corresponding to Bonferroni correction for 56 tests). Compared with homozygous participants without the risk allele, homozygous carriers of the rs7164727 (LOC100287559: 0.42 kg; 95% CI, 0.31-0.53 kg, P = 4.00 × 10-4) and rs12940622 (RPTOR: 0.35 kg; 95% CI, 0.18-0.52 kg; P = 1.86 × 10-5) risk alleles had a lower reduction of body weight, whereas carriers of the rs13201877 (IFNGR1: 0.65 kg; 95% CI, 0.51-0.79 kg; P = 2.39 × 10-5), rs10733682 (LMX1B: 0.45 kg; 95% CI, 0.27-0.63 kg; P = 6.37 × 10-4), and rs2836754 (ETS2: 0.56 kg; 95% CI, 0.38-0.74 kg; P = 1.51 × 10-4) risk alleles were associated with a greater reduction of body weight after adjustment for age and sex.Conclusions and relevanceGenes appear to play a minor role in weight reduction by lifestyle in children with overweight or obesity. The findings suggest that environmental, social, and behavioral factors are more important to consider in obesity treatment strategies.

Project description:Aims Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of the metabolic syndrome (MetS). Lifestyle-induced weight loss (WL) is regarded as an efficient therapy to reverse MetS and to prevent disease progression. The objective of this study was to investigate if lifestyle-induced WL modulates the gut microbiome and its interaction with the host. Methods We analyzed and compared the fecal metaproteome of 33 individuals with MetS in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort (ICTRP Trial Number: U1111-1158-3672). Results The 6-month WL intervention resulted in reduced BMI (-13.9%), increased insulin sensitivity (HOMA-IR; -53.70%) and reduced levels of circulating CRP (-66.86%), indicating MetS reversal. The metaprotein spectra of the host revealed a decrease of human proteins associated with gut inflammation and reduced abundance of human pancreatic alpha-amylase. Surprisingly, taxonomic analysis of the fecal metaproteome revealed only minor changes in the bacterial composition with an increase of low-abundant families (Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae, Verrucomicrobiaceae). Yet, we detected increased abundance of microbial metaprotein spectra that correspond to enhanced hydrolysis of complex carbohydrates (endoglucanase A, β-1,4-mannooligosaccharide phosphorylase, galactokinase, 5-keto-D-gluconate 5-reductase), indicating functional changes of the gut microbiome. Conclusions Our results indicate that lifestyle induced WL may improve interaction between the gut microbiome and the host in individuals with MetS, while bacterial composition remained almost stable. Metaproteome analysis of host proteins reveals reduced gut inflammation whereas microbial metaprotein spectra indicate functional changes towards degradation of complex carbohydrates. The filenames correspond to the ID of the patient (1-33), whereas “C” corresponds to baseline and “ABC” to weight loss.

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

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