Use of human PBMC to analyse the impact of obesity on lipid metabolism and metabolic status: a proof-of-concept pilot study

Andrea Costa,Miquel Fiol,Marian Martín,Jadwiga Konieczna,Andreu Palou,Paula Oliver,Dora Romaguera,Bàrbara Reynés

doi:10.1038/s41598-021-96981-6

Abstract

Peripheral blood mononuclear cells (PBMC) are widely used as a biomarker source in nutrition/obesity studies because they reflect gene expression profiles of internal tissues. In this pilot proof-of-concept study we analysed in humans if, as we previously suggested in rodents, PBMC could be a surrogate tissue to study overweight/obesity impact on lipid metabolism. Pre-selected key lipid metabolism genes based in our previous preclinical studies were analysed in PBMC of normoglycemic normal-weight (NW), and overweight-obese (OW-OB) subjects before and after a 6-month weight-loss plan. PBMC mRNA levels of CPT1A, FASN and SREBP-1c increased in the OW-OB group, according with what described in liver and adipose tissue of humans with obesity. This altered expression pattern was related to increased adiposity and early signs of metabolic impairment. Greater weight loss and/or metabolic improvement as result of the intervention was related to lower CPT1A, FASN and SREBP-1c gene expression in an adjusted linear mixed-effects regression analysis, although no gene expression recovery was observed when considering mean comparisons. Thus, human PBMC reflect lipid metabolism expression profile of energy homeostatic tissues, and early obesity-related alterations in metabolic at-risk subjects. Further studies are needed to understand PBMC usefulness for analysis of metabolic recovery in weigh management programs.

Highlights

Peripheral blood mononuclear cells (PBMC) are widely used as a biomarker source in nutrition/obesity studies because they reflect gene expression profiles of internal tissues
Our group has widely contributed to demonstrate the utility of PBMC as a surrogate tissue and as a source of biomarkers to study lipid metabolism alteration, which occurs in obesity, as well its recovery in a situation of weight loss
We assessed the utility of PBMC in humans as biological material to be used in the analysis of lipid metabolism alteration that occurs in obesity, as well as its recovery in a situation of weight loss

Summary

Introduction

Peripheral blood mononuclear cells (PBMC) are widely used as a biomarker source in nutrition/obesity studies because they reflect gene expression profiles of internal tissues. Impaired PBMC expression of these genes can be recovered as results of dietary interventions, so we proposed them as biomarkers of weight loss and metabolic improvement[13,14] With this background, in this study, we aimed to check the utility of PBMC in humans as a tool to analyse the impact of overweight and obesity on the expression of key genes of lipid metabolism. In this study, we aimed to check the utility of PBMC in humans as a tool to analyse the impact of overweight and obesity on the expression of key genes of lipid metabolism This would allow using these cells as an obtainable source of transcriptomic biomarkers to deepen into the knowledge of adaptations in response to increased adiposity that occur in internal homeostatic tissues, without the need of using invasive biopsies. PBMC expression patterns were correlated with relevant anthropometric and clinical parameters to establish the potential usefulness of the analysed genes as biomarkers of metabolic impairment/recovery

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Conclusion