Impaired CPT1A Gene Expression Response to Retinoic Acid Treatment in Human PBMC as Predictor of Metabolic Risk

Abstract

Ex vivo human peripheral blood mononuclear cell (PBMC) systems offer the possibility to test transcriptomic effects of food bioactive compounds with potential health effects. We investigated all-trans retinoic acid (ATRA) effect on mRNA expression of key lipid metabolism and inflammatory genes in PBMCs from normal-weight (NW) and overweight-obese (OW-OB) men with different metabolic syndrome-related features. PBMCs were incubated with 10 µM ATRA and mRNA levels of selected genes were analyzed using real-time RT-qPCR. Human ex vivo PBMCs responded to ATRA treatment, but the response for some genes was dependent on body mass index (BMI), with a lower response in PBMC from OW-OB than from NW donors. Moreover, gene expression response was affected by circulating high-density lipoprotein (HDL)-cholesterol levels. Particularly, the response to ATRA of CPT1A, previously reported as a sensitive metabolic risk predictive biomarker, was dependent on HDL levels and not on BMI, being impaired in those individuals with lower HDL levels, specifically in OW-OB. Thus, PBMCs’ insensitivity to ATRA, which can be considered as indicative of impaired metabolism, was observed in individuals with higher metabolic risk (OW-OB with low HDL levels). In conclusion, an ex vivo human PBMC system indicates that ATRA response could be influenced by metabolic syndrome features. Moreover, our study reinforces the role of CPT1A as a marker of metabolic risk and points to plasmatic HDL-cholesterol levels as a parameter to take into consideration when the effects of nutritional factors and/or dietary interventions on humans are under study. Further studies including women are required to detect potential gender differences in the observed effects.

Role of cellular retinol‐binding protein, type 1 and retinoid homeostasis in the adult mouse heart: A multi‐omic approach

“…69 Previous studies have shown that RA treatment activates fatty acid oxidation, leading to increased expression of Cpt1a expression. [70][71][72] Our analysis also revealed differences in the levels of various phospholipid species. These differences were seen in comparing LV versus RV and also in comparing the two genotypes, Rbp1 -/and WT mice.…”

“…CPT1A is an important biomarker of diet‐related metabolic alterations, 67,68 and has also been identified as a potential biomarker of heart disease detection 69 . Previous studies have shown that RA treatment activates fatty acid oxidation, leading to increased expression of Cpt1a expression 70–72 …”

Association Between Retinoid X Receptor Gene Variants and Dyslipidemia Risk in an Iranian Population

“…Vimaleswaran et al's findings demonstrated that variations in the RXR gene, including VDR (22 tag SNPs) and RXRG (23 tag SNPs), did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes [20]. The relationship between RXRA polymorphisms and lipid and lipoprotein levels has been widely considered [7,[21][22][23]. In a study, Lima et al reported that polymorphisms in the RXRA gene (rs11381416) influence the triglycerides level in a Southern Brazilian population [7].…”

Genomics and Personalized Nutrition

“…The purpose of this Special Issue was to expand and add to the research which uses genomics technologies in the development of personalized nutrition recommendations. This Special Issue on “Genomics and Personalized Nutrition” features five original articles [ 5 , 6 , 7 , 8 , 9 ] and four reviews [ 10 , 11 , 12 , 13 ] which examine two facets of personalized nutrition: 1—genomics and food bioactive compounds; and 2—genetic variations and diet interactions.…”

“…Overall, this study suggests that milt herring is a novel marine ingredient to help fight against metabolic syndrome. Secondly, Cifre et al, 2020 [ 6 ] show that the administration of all-trans retinoic acid regulates the expression of key inflammatory and lipid metabolism genes in an ex vivo system of peripheral blood mononuclear cells in normal-weight and overweight–obese subjects. These studies are excellent examples of the use of various genomics techniques to further understand the effects of foods on health and to adapt our current recommendations.…”