Many diseases are associated with obesity, and multiple studies have documented associations between body mass index (BMI), a surrogate measure of adiposity, and metabolites that are correlated with increased risk of these diseases.  However, BMI does not distinguish between elevated weight because of adipose or lean mass.  As a result, it is not clear if the biomarkers of obesity identified to date are correlated with body composition.  McClain and colleagues conducted a study designed to determine the contribution of fat and lean mass on BMI-metabolite correlations and to identify novel biomarkers of fat and lean mass.  Results from their work are published in the February 2022 issue of The Journal of Nutrition.

Data were collected from postmenopausal women (n = 304) enrolled in the Alberta Physical Activity and Breast Cancer Prevention Trial.  Height and weight were measured and DXA was used to estimate fat and lean mass.  Serum metabolites were determined and correlations between 1052 metabolites and BMI were determined after adjusting for age, smoking and site.  Correlations with fat mass index (FMI) and lean mass index (LMI) were also determined using the same approaches, with mutual adjustment to determine their independent effects.

There were 53 BMI-correlated metabolites identified, of which 21 were robustly correlated and 25 that were modestly correlated with FMI.  Of the 53 original metabolites identified, 10 were more correlated with LMI than with FMI.  There were 6 metabolites that were highly correlated with FMI and two with LMI, but were not correlated with BMI.  Those metabolites correlated with FMI and LMI were in opposite directions, as compared with BMI-correlated metabolites which were mostly in the same direction. 

These observations led the authors to suggest that a thorough evaluation of the components of body composition in addition to BMI is necessary to generate a more accurate assessment of the association between body composition and metabolites.  They concluded that to understand the mechanisms underlying the association between obesity and disease, it is necessary to correctly characterize the relationships between metabolites and the components of body composition.


Kathleen M McClain, Christine M Friedenreich, Charles E Matthews, Joshua N Sampson, David P Check, Darren R Brenner, Kerry S Courneya, Rachel A Murphy, Steven C Moore, Body Composition and Metabolomics in the Alberta Physical Activity and Breast Cancer Prevention Trial, The Journal of Nutrition, Volume 152, Issue 2, February 2022, Pages 419–428,

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