SEARCHCOHORTepidemiology, cardiology

cohort·epidemiology, cardiology, endocrinology, internal medicine, observational study·PMC10599989

Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass

International Journal of Obesity (2005) · 8 authors, 7 centres

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It identified five proteins not previously linked to body size.

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The investigators measured fat mass via dual-energy X-ray absorptiometry (DXA) to calculate a fat mass index (FMI) and assessed 276 circulating proteins. Using a discovery and replication design, random forest analysis and multivariable linear regression, they identified 66 proteins significantly associated with FMI after adjustment for confounders. Five proteins (CLSTN2, KLK10, SSC4D, TLT-2, and IL-6RA) were not previously associated with body size. Principal component analysis revealed protein patterns involved in metabolism and inflammation. The findings suggest that objectively measured fat mass has a broad association with the circulating proteome.

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cohort

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epidemiology

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ORIGINAL PAPER

PMC10599989

Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass

International Journal of Obesity (2005)

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ABSTRACT

Abstract Background The underlying molecular pathways for the effect of excess fat mass on cardiometabolic diseases is not well understood. Since body mass index is a suboptimal measure of body fat content, we investigated the relationship of fat mass measured by dual-energy X-ray absorptiometry with circulating cardiometabolic proteins. Methods We used data from a population-based cohort of 4950 Swedish women (55–85 years), divided into discovery and replication samples; 276 proteins were assessed with three Olink Proseek Multiplex panels. We used random forest to identify the most relevant biomarker candidates related to fat mass index (FMI), multivariable linear regression to further investigate the associations between FMI characteristics and circulating proteins adjusted for potential confounders, and principal component analysis (PCA) for the detection of common covariance patterns among the proteins. Results Total FMI was associated with 66 proteins following adjustment for multiple testing in discovery and replication multivariable analyses. Five proteins not previously associated with body size were associated with either lower FMI (calsyntenin-2 (CLSTN2), kallikrein-10 (KLK10)), or higher FMI (scavenger receptor cysteine-rich domain-containing group B protein (SSC4D), trem-like transcript 2 protein (TLT-2), and interleukin-6 receptor subunit alpha (IL-6RA)). PCA provided an efficient summary of the main variation in FMI-related circulating proteins involved in glucose and lipid metabolism, appetite regulation, adipocyte differentiation, immune response and inflammation. Similar patterns were observed for regional fat mass measures. Conclusions This is the first large study showing associations between fat mass and circulating cardiometabolic proteins. Proteins not previously linked to body size are implicated in modulation of postsynaptic signals, inflammation, and carcinogenesis. Subject terms: Risk factors, Medical research

CITATION EXPORT

Olga E Titova, Carl Brunius, Eva Warensjö Lemming et al.. Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass. International Journal of Obesity (2005). (2023). https://doi.org/10.1038/s41366-023-01351-z

AUTHORS

8 · 7 CENTRES

Olga E Titova, Carl Brunius, Eva Warensjö Lemming, Karl Stattin, John A Baron, Liisa Byberg, Karl Michaëlsson, Susanna C Larsson

1Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
2Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden
3Department of Food studies, nutrition and dietetics, Uppsala University, Uppsala, Sweden
4Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden
5Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC USA
6Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC USA
7Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden