Plasma Metabolomic Profiling in 1391 Subjects with Overweight and Obesity from the SPHERE Study
Obesity is a risk factor for a wide range of diseases, from diabetes and cardiovascular problems, to neurodegenerative diseases and various types of cancer. Improving our understanding of the biochemical processes associated with overweight and obesity are therefore important. Better knowledge of how obesity affects disease could help predict individual health outcomes.
Researchers at the University of Milan and the Policlinico of Milan published a new study, which replicates previous findings and improves knowledge of how metabolism is increasingly dysregulated with a growing degree of obesity. The researchers investigated the plasma metabolome of 1391 participants of the SPHERE study, using biocrates’ AbsoluteIDQ® p180 kit. Participants were split into four groups according to Body Mass Index (BMI <30; BMI 30-34.9; BMI 35-39.9; BMI ≥40).
Significant associations between metabolite levels and BMI were detected for dozens of metabolites. Among the positively associated metabolites, the amino acids tyrosine, valine and isoleucine were among the most strongly dysregulated substances. Negatively associated metabolites were found to include a large range of lipids, especially PC ae lipids. Several of the altered metabolites show a clear association with the degree of obesity.
The discussion of results highlights the reproducibility of the chosen metabolomics approach by relating findings to several papers which used the same kit, including a previously published study on reference values in healthy individuals. Probably owing to the relatively large study size, previously unknown associations between selected phosphatidylcholines and obesity have been reported for the first time.
Finally, the study confirms that although metabolite levels are clearly influenced by obesity, the effect varies from person to person. This variability could help predict obesity-related health outcomes, by increasing our understanding of why some obese individuals remain healthy for many decades, while others are affected by myocardial infarction, stroke, chronic kidney disease, colorectal cancer and other diseases.
Several interesting parallels can be drawn between the findings of the SPHERE study and previous studies that have tried to predict outcomes:
-The majority of lipids found to be inversely associated with coronary heart disease are among the lipids significantly reduced in obesity. (https://biocrates.com/circulating-metabolites-predict-coronary-heart-disease-risk/)
-Kühn et al. (BMC Medicine 2016; 14:13) also found PC ae 30:0 to be negatively correlated with BMI, with higher levels of this lipid associated with an increased risk for common cancers.
-The finding that beta-oxidation of very-long chain fatty acids (VLCFA) is among the pathways strongly affected by obesity may be relevant for cancer immunotherapy: Mock et al. proposed VLCFA as biomarkers for the prediction of response to immune checkpoint inhibitor therapy.(https://biocrates.com/make-sure-your-drug-fits-your-cancer/)
The impact of obesity on response to immune checkpoint inhibitor therapy is also the subject of discussion, albeit with conflicting results.
In summary, this paper highlights the complex relationship between obesity and metabolism, confirming previous findings and finding new associations. The results deepen our knowledge of how obesity is related to chronic diseases and how metabolism defines clinical outcomes.
Frigerio G, Favero C, Savino D et al.: Plasma Metabolomic Profiling in 1391 Subjects with Overweight and Obesity from the SPHERE Study. (2021) Metabolites | https://doi.org/10.3390/metabo11040194