Abstract

The interplay between fat mass and lean mass within human metabolism is not completely understood. We aimed to identify specific circulating metabolomic profiles associated with these body composition compartments. Cross-sectional analyses were conducted over 236 adults with overweight/obesity from the Satiety Innovation (SATIN) study. Body composition was assessed by dual-energy X-ray absorptiometry. A targeted multiplatform metabolite profiling approach was applied. Associations between 168 circulating metabolites and the body composition measures were assessed using elastic net regression analyses. The accuracy of the multimetabolite weighted models was evaluated using a 10-fold cross-validation approach and the Pearson’s correlation coefficients between metabolomic profiles and body compartments were estimated. Two different profiles including 86 and 65 metabolites were selected for % body fat and lean mass. These metabolites mainly consisted of lipids (sphingomyelins, phosphatidylcholines, lysophosphatidylcholines), acylcarnitines, and amino acids. Several metabolites overlapped between these body composition measures but none of them towards the same direction. The Pearson correlation coefficients between the metabolomic profiles and % body fat or lean mass were 0.80 and 0.79, respectively. Our findings suggest alterations in lipid metabolism, fatty acid oxidation, and protein degradation with increased adiposity and decreased lean body mass. These findings could help us to better understand the interplay between body composition compartments with human metabolic processes.

Highlights

  • IntroductionIncreased prevalence of obesity, assessed by body mass index (BMI), is one of the largest health concerns globally being a major risk factor for a number of prevalent chronic diseases [1]

  • body mass index (BMI) is an indirect estimate of adiposity as it does not distinguish between fat mass and lean mass

  • Given the role of circulating sphingolipids in atherosclerosis development [19], the increased circulating concentrations of SMs with two double bonds and decreased concentrations with one double bond associated with increased adiposity we found in our analysis could partially explain the increased cardiovascular risk associated with excessive adiposity

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Summary

Introduction

Increased prevalence of obesity, assessed by body mass index (BMI), is one of the largest health concerns globally being a major risk factor for a number of prevalent chronic diseases [1]. The underlying mechanisms linking these two compartments of body composition with health outcomes are not fully understood. Prior studies have identified different circulating metabolites such as amino acids, acylcarnitines, or lipid species associated with body fat [6,7,8], lean mass [7,9,10,11], and metabolic risk [6,12,13]. To date, limited metabolomic-analysis has been conducted using combinations of different metabolomic platforms to cover a wide range of metabolites and examine their association with these body composition compartments. A comprehensive metabolite profiling (metabolomics) may provide a deeper understanding of the interplay between fat mass and lean mass with human metabolism

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