Stephanie Zylla

Background: Physical activity supports weight regulation and metabolic health, but its timing in relation to obesity and diabetes remains unclear. We aimed to assess the diurnal timing of physical activity and its association with obesity and diabetes. Methods: We cross-sectionally analyzed hip-worn accelerometry data from 61,116 participants aged 20–75 in the German National Cohort between 2015 and 2019. We divided physical activity into sex- and age-standardized quartiles of total morning (06:00–11:59), afternoon (12:00–17:59), evening (18:00–23:59), and nighttime (00:00–06:00) physical activity. Using multivariable logistic regression, we estimated associations of physical activity timing with obesity (BMI ≥ 30.0 kg/m²) and diabetes (self-reported or HbA1c ≥ 6.5%). We accounted for sex, age, study region, education, employment, risky alcohol use, smoking, night shift work, and sleep duration. Results: High afternoon (top vs. bottom quartile, OR: 0.36, 95% CI: 0.33–0.38) and evening physical activity (OR: 0.45, 95% CI: 0.42–0.48) showed lower obesity odds than high morning activity (OR: 0.71, 95% CI: 0.66–0.76), whereas nighttime activity increased obesity odds (OR: 1.58, 95% CI: 1.48–1.68). Associations were similar for diabetes, with the lowest odds for afternoon (OR: 0.47, 95% CI: 0.42–0.53), followed by evening (OR: 0.56, 95% CI: 0.50–0.62) and morning activity (OR: 0.80, 95% CI: 0.71–0.89), and higher odds for nighttime activity (OR: 1.43, 95% CI: 1.29–1.58). Findings were not modified by employment status, night shift work, and sleep duration. Conclusions: Our cross-sectional findings require longitudinal corroboration but suggest afternoon and evening activity provide greater metabolic health benefits than morning activity, while nighttime activity is discouraged.

Background and objectives: Various cross-sectional studies have observed an association between high circulating concentrations of the adipokine chemerin and an unfavorable metabolic profile. However, the prognostic value of chemerin for the risk of associated diseases and mortality was examined only in a few studies mostly using small and highly selected patient populations. We aimed to analyze the association between plasma chemerin concentrations and all-cause as well as cause-specific mortality in the general population. Study design and methods: From the Study of Health in Pomerania (SHIP), participants of two independent cohorts (SHIP-START-1 [n = 3037], SHIP-TREND-0 [n = 4193]) were followed up for 15 and 9 years (median), respectively. The association between plasma chemerin and all-cause mortality was analyzed using multivariable Cox proportional hazard regression models. Additionally, cause-specific hazards for cardiovascular disease (CVD) and cancer mortality were modeled considering competing events. Results: A total number of 507 and 208 deaths occurred during follow-up in SHIP-START-1 and SHIP-TREND-0, respectively. Multivariable regression analyses revealed a significant association between high plasma chemerin concentrations and greater overall mortality that was independent of major confounders. Each 30 ng/mL increase in chemerin was associated with a 17% higher risk of all-cause mortality (95%-confidence interval: 1.10–1.26). Cause-specific analyses further showed that the chemerin concentration was significantly associated with cancer mortality but not with CVD mortality. Conclusion: The present study detected a positive association between plasma chemerin concentrations and all-cause mortality in a large population-based study sample. Cause-specific analyses have shown that chemerin is likely to play a decisive role in cancer-related deaths. However, a direct association with cardiovascular mortality could not be established.

Adipokines and cardiorespiratory fitness (CRF) are associated with the (patho)physiology of cardiometabolic diseases. Whether CRF and adipokines are related is unclear. We investigated associations of CRF with leptin, adiponectin, chemerin, resistin and vaspin. Data from the population-based Study of Health in Pomerania was used (n=1,479; median age 49 years; 51% women). Cardiopulmonary exercise testing was used to measure CRF. Circulating adipokine concentrations were measured by enzyme-linked immunosorbent assay. The association between CRF and adipokines was assessed using multivariable sex-specific quantile regression models. Higher maximum oxygen uptake was significantly associated with lower leptin (men:−0.11 ng/ml; 95%-confidence interval [CI]:−0.18 to−0.03 ng/ml; p<0.005; women:−0.17 ng/ml; 95%-CI:−0.33 to−0.02 ng/ml; p<0.05) and chemerin (men:−0.26 ng/ml; 95%-CI:−0.52 to−0.01 ng/ml; p<0.05; women:−0.41 ng/ml; 95%-CI:−0.82 to−0.01 ng/ml; p<0.05) as well as higher adiponectin concentrations (men: 0.06 µg/ml; 95%-CI: 0.02 to 0.11 µg/ml; p<0.05; women: 0.03 µg/ml; 95%-CI:−0.05 to 0.10 µg/ml; p=0.48). We found that CRF was inversely associated with leptin and chemerin in both sexes and positively associated with adiponectin only in men.

The Study of Health in Pomerania (SHIP), a population-based study from a rural state in northeastern Germany with a relatively poor life expectancy, supplemented its comprehensive examination program in 2008 with whole-body MR imaging at 1.5 T (SHIP-MR). We reviewed more than 100 publications that used the SHIP-MR data and analyzed which sequences already produced fruitful scientific outputs and which manuscripts have been referenced frequently. Upon reviewing the publications about imaging sequences, those that used T1-weighted structured imaging of the brain and a gradient-echo sequence for R2* mapping obtained the highest scientific output; regarding specific body parts examined, most scientific publications focused on MR sequences involving the brain and the (upper) abdomen. We conclude that population-based MR imaging in cohort studies should define more precise goals when allocating imaging time. In addition, quality control measures might include recording the number and impact of published work, preferably on a bi-annual basis and starting 2 years after initiation of the study. Structured teaching courses may enhance the desired output in areas that appear underrepresented.

The use of oral contraceptives (OCs) has been associated with elevated blood cortisol concentrations. However, metabolic downstream effects of OC intake are not well described. Here, we aimed to determine if the blood metabolome is associated with the use of OCs and to estimate if these associations might be statistically mediated by serum cortisol concentrations. Plasma metabolites measured with the Biocrates AbsoluteIDQ p180 Kit and serum cortisol concentrations measured by an immunoassay were determined in 391 premenopausal women (116 OC users) participating in two independent cohorts of the Study of Health in Pomerania (SHIP). After correction for multiple testing, 27 metabolites were significantly associated with OC intake in SHIP-TREND (discovery cohort), of which 25 replicated in SHIP-2. Inter alia, associated metabolites included 12 out of 38 phosphatidylcholines with diacyl residue, 7 out of 14 lysophosphatidylcholines and 5 out of 21 amino acids. The associations with phosphatidylcholines were statistically mediated by cortisol, whereas lysophosphatidylcholines showed no mediation effect. The results represent a step toward a better understanding of the metabolic consequences of OC intake. Connecting cortisol with metabolic consequences of OC intake could help to understand the mechanisms underlying adverse effects. The blood metabolome may serve as a biomarker for identifying users at high risk for developing such adverse effects.

Objective: This study provides a comprehensive overview of the associations of five adipokines (adiponectin, chemerin, galectin‐3, leptin, and resistin) with fat deposits, behavioral risk factors, and metabolic phenotypes.Methods: Using multivariable linear and logistic regression models, cross‐sectional data from 4,116 participants of the population‐based Study of Health in Pomerania were analyzed.Results: Participants with obesity showed higher chemerin, galectin‐3, and leptin but showed lower adiponectin concentrations. Independently of other fat compounds, liver fat content, visceral adipose tissue, and subcutaneous adipose tissue (SAT) were inversely associated with adiponectin. Independent positive associations of liver fat content and SAT with chemerin as well as of SAT with galectin‐3 and leptin were observed. Physically inactive participants had higher chemerin and leptin concentrations. Smokers had higher chemerin and galectin‐3 as well as lower leptin. Alcohol consumption was associated with adiponectin (positive) and resistin (inverse). All adipokines were associated with at least one lipid marker. Associations with glucose metabolism were seen for adiponectin, chemerin, galectin‐3, and leptin.Conclusions: High adiponectin concentrations were related to favorable metabolic conditions, whereas high chemerin, galectin‐3, and leptin were associated with an unfavorable metabolic profile. High leptin seems to be primarily indicative of obesity, whereas high adiponectin and chemerin are associated with a broader range of metabolic phenotypes.

Objective: Chemerin and adiponectin are adipokines assumed to be involved in the development of metabolic syndrome-related phenotypes like hepatic steatosis. We aimed to evaluate the associations of circulating chemerin and adiponectin concentrations with liver enzymes, liver fat content, and hepatic steatosis in the general population. Methods: Data of 3951 subjects from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Hepatic steatosis was assumed when either a hyperechogenic liver (assessed via ultrasound) or a magnetic resonance imaging (MRI)-quantified liver fat content >5% was present. Adjusted sex-specific quantile and logistic regression models were applied to analyze the associations of chemerin and adiponectin with liver enzymes, liver fat content and hepatic steatosis. Results: The observed associations of chemerin and adiponectin with liver enzymes were very divergent depending on sex, fasting status and the specific enzyme. More consistent results were seen in the analyses of these adipokines in relation to MRI-quantified liver fat content. Here, we observed inverse associations to adiponectin in both sexes as well as a positive (men) or U-shaped (women) association to chemerin. Similarly, the MRI-based definition of hepatic steatosis revealed strongly consistent results: in both sexes, high chemerin concentrations were associated with higher odds of hepatic steatosis, whereas high adiponectin concentrations were associated with lower odds. Conclusion: Our results suggest a role of these adipokines in the pathogenesis of hepatic steatosis independent of metabolic or inflammatory disorders. However, experimental studies are needed to further clarify the underlying mechanisms and the inter-play between adipokine concentrations and hepatic steatosis.

The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure. Apart from this and only recently recognized, NT-proBNP levels associate with higher HDL- and lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). We complemented this investigation with a state-of-the-art untargeted metabolomics approach. Lipoprotein particles were determined by 1H-NMR spectroscopy in 872 subjects without self-reported diabetes from the population-based Study of Health in Pomerania (SHIP)-TREND with available NT-proBNP measurements. Comprehensive metabolomics data for plasma and urine samples were obtained. Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine. An increase in serum NT-proBNP was associated with a benefical lipoprotein profile, including a decrease in VLDL, IDL and LDL-particles along with an increase in large HDL particles. These findings were replicated in a second independent cohort. Serum concentrations of NT-proBNP showed significant inverse associations with seven plasma metabolites while associations with 39 urinary metabolites, mostly comprising amino acids and related intermediates, were identified. Mediation analyses revealed adiponection as mediating factor for the associations observed with lipoproteins particles. Most of the metabolic changes associated with NT-proBNP implicate significant influence on the blood lipid profile besides vasodilatory and the diuretic action of BNP signaling. Our data suggest that the more favorable lipoprotein profile as associated with elevated NT-proBNP concentrations in mainly cardiac healthy individuals might relate to adiponectin signaling indicating even indirect cardio-protective effects for NT-proBNP.

Objective—: Chemerin has been shown to be associated with inflammation and metabolic syndrome, which are in turn leading risk factors for atherosclerosis. A few clinical studies have concentrated on the role of chemerin in atherosclerosis but revealed divergent findings. Therefore, we aimed to investigate the association of plasma chemerin levels with different subclinical measurements of atherosclerosis in a population-based sample. Approach and Results—: Linear and logistic regression models with different atherosclerotic parameters as subclinical outcomes were applied to analyze data from 4003 subjects of the SHIP (Study of Health in Pomerania). After adjustment for metabolic and inflammatory parameters, these models revealed no association of chemerin with carotid intima-media thickness, carotid plaque, or carotid stenosis but a significant inverse association between chemerin and ankle-brachial index. In detail, logistic regression analysis showed that a 25-ng/mL increase in chemerin was associated with a 30% higher odd (95% confidence interval, 1.20–1.41) of having an ankle-brachial index value below the 25th age- and sex-specific quartile. Conclusions—: Our analyses revealed a modest inverse association between chemerin and ankle-brachial index that remained consistent after adjustment for metabolic and inflammatory parameters. The association of chemerin with carotid intima-media thickness, carotid plaque, or carotid stenosis was not significant after adjustment for the same confounder set. The investigated subclinical atherosclerotic parameters are representative for the atherosclerotic burden of different arterial regions and different disease stages. Thus, our results might suggest that the value of chemerin as a marker of higher atherosclerotic risk differs depending on the affected arterial region and disease stage.

Background, objective: Adipose tissue is known to secrete a multitude of bioactive adipokines and it seems that the majority of these adipokines is implicated in the pathogenesis of obesity and associated metabolic diseases. Existing research studies mostly concentrated on one or two adipokines and therefore, comparisons of the involvement of different adipokines in these disorders are difficult. Furthermore, associations of circulating adipokine levels with different fat compounds or lifestyle factors are mostly missing in existing studies. This study aimed to provide a comprehensive overview of the associations of a panel of circulating adipokines (adiponectin, leptin, resistin, chemerin, vaspin) with metabolic parameters and renal function in a well characterized large population-based study. Methods: Data from 4129 subjects of the Study of Health in Pomerania were analyzed. Residual method was used to investigate the associations of MRI-quantified liver fat content as well as visceral (VAT) and subcutaneous adipose tissue (SAT) with circulating adipokine levels. Furthermore, multivariable regression models were applied to examine the associations of adipokine concentrations with lifestyle factors (smoking, alcohol consumption, physical inactivity), metabolic phenotypes, and renal function. Results: Independently of other fat compounds, liver fat content, SAT, and VAT were inversely associated with adiponectin. Furthermore, an independent positive association of liver fat content and SAT with chemerin was observed. The strongest independent association was detected between SAT and leptin. Physically inactive subjects had higher chemerin and leptin levels and smoking led to higher chemerin as well as lower adiponectin and leptin concentrations. Alcohol consumption was associated with adiponectin (positive) and resistin (inverse). Obese subjects showed increased chemerin, leptin, and vaspin levels, but decreased adiponectin concentrations. All adipokines were associated with lipid markers, whereas associations with parameters of glucose metabolism were only seen for adiponectin, chemerin, and leptin. An inverse association of similar strength was observed between chemerin, leptin as well as resistin and estimated glomerular filtration rate (beta −0.2, P<0.01). Conclusion: Our results indicate that the associations between different circulating adipokine levels and metabolic risk factors as well as renal function significantly differ. In general, high adiponectin levels seem to have a protective role whereas increased chemerin, leptin, resistin, or vaspin concentrations seem to be disadvantageous for the investigated alterations. Leptin concentrations play a key role during obesity, whereas for other metabolic disorders adiponectin and chemerin levels seem to be more meaningful. During processes of renal disease circulating chemerin, leptin, and resistin levels might be of similar importance.