A Global Transcriptomic Analysis Reveals Body Weight‐Specific Molecular Responses to Chronic Orange Juice Consumption in Healthy Individuals

ABSTRACT Consumption of orange juice (OJ) has been linked to a lower incidence of cardiovascular diseases. However, molecular mechanisms underlying these health benefits remain unclear. This study aimed to investigate the molecular pathways involved in the health benefits of chronic OJ consumption through global transcriptomic approach in peripheral blood mononuclear cells (PBMCs). Healthy volunteers consumed 500 mL of OJ daily for 60 days. PBMCs were isolated from the blood, and the gene expression profiling was performed using Clariom microarrays. Genomic analysis revealed 1705 differentially expressed genes, including IL6, IL1β involved in inflammation, GSK3B, RIPK1 related to lipid metabolism, and NAMPT, NLRP3 involved in blood pressure regulation. Moreover, the expression of 66 miRNAs, 19 long‐non‐coding RNAs (lncRNAs), and 67 small nucleolar RNAs (snoRNAs) was modulated. Moreover, subgroup analysis revealed different transcriptomic responses between normal‐weight (NW) and overweight (OW) individuals. Genes related to lipid metabolism and adipogenesis were differentially expressed only in OW, including GSK3B, GRK6, miR‐548i, and miR‐1292‐3p. In contrast, genes related to the inflammation process, like STAT3, MAPK, and miRNAs (miR‐1185‐2‐5p), were observed only in NW. These findings suggest that body weight may influence molecular response to bioactive compounds in OJ and provide information for personalized recommendations on the consumption of flavonoid‐rich foods.