Chronic effect of blood orange juice intake on the microRNA expression profile and inflammatory response in overweight women

Author(s)

Vinícius Cooper Capetini

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Saúde Pública (FSP/CIR)
• Defense date: 2021-08-10

Examining board members

Marcelo Macedo Rogero; Renata Guerra de Sá Cota; Eduardo Purgatto; Silvana Auxiliadora Bordin da Silva

• Advisor: Marcelo Macedo Rogero

Abstract

Introduction: Obesity is directly involved in the etiology of chronic non-communicable diseases (NCD). The excessive intake of nutrients associated with obesity culminates in the activation of pro-inflammatory signaling pathways in different parts of the body, causing systemic, chronic, and low-intensity inflammation. microRNA (miRNA) act as modulators and biomarkers of inflammatory processes and the analysis of their expression can contribute to the identification of the risk of NCDs. Orange (Citrus sinensis) is the most produced fruit in Brazil, containing significant concentrations of flavonoids, vitamin C, and carotenoids, which have antioxidant and anti-inflammatory activity. In this context, blood orange stands out, which in addition to the common nutritional compounds in Citrus, it has anthocyanins. Objective: To investigate the effect of chronic Moro blood orange juice intake on the inflammatory response and miRNA expression profile in plasma and peripheral blood mononuclear cells (PBMC) in overweight women. Methods: Chronic intervention study in women (n = 20) aged 18 to 40 years old, diagnosed with overweight (body mass index = 25.0 to 29.9 kg/m2). For four weeks, the volunteers ingested, daily, 500 mL of Moro blood orange juice, with blood samples collected at baseline and 2 and 4 weeks after the beginning of the experimental protocol. The following analyses were carried out: characterization of Moro blood orange juice; anthropometric measurements; blood pressure measurement; dietary intake assessment; determination of plasma concentrations of glucose, insulin, lipopolysaccharides, lipopolysaccharide-binding protein, soluble cluster of differentiation 14, and inflammatory biomarkers [interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-&alpha;), monocyte chemoattractant protein-1, soluble intercellular adhesion molecule (sICAM)-1 and soluble vascular cell adhesion molecule (sVCAM)-1]; and determination of serum concentrations of lipid profile, C-reactive protein, fibrinogen, D-dimer, gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, amylase, urea, creatinine, and minerals. Were also analyzed the expression of miRNA in plasma and PBMC; the expression of genes TNF, nuclear factor kappa B p50 subunit (NFKB1), NF-&kappa;B p65 subunit (RELA), NF-&kappa;B inhibitor alpha (NFKBIA), IL1, IL6, IL10, and toll-like receptors (TLR2 e TLR4); and the content and phosphorylation of proteins NF-&kappa;B, I&kappa;B-&alpha;, c-Jun N-terminal kinase (JNK), inhibitor of NF-&kappa;B kinase subunit beta (IKK-&beta;) and transforming growth factor &beta;-activated kinase 1 (TAK1). Results: Moro blood orange juice intake increased vitamin C consumption (p < 0.001), phospho-JNK/JNK ratio (p < 0.05), and miRNA expression in plasma [miR-144-3p (p = 0.02)] and in PBMC [miR-424-5p (p = 0.002), miR-144-3p (p = 0.006), and miR-130b-3p (p = 0.03)]. Conversely, it decreased the protein content of NF-&kappa;B (p < 0.05) and the expression of let-7f-5p (p = 0.007) and miR-126-3p (p = 0.04) in PBMC. However, no significant changes were observed in the expression of genes that encode proteins involved in the inflammatory response and the anthropometric and biochemical parameters analyzed at the end of the experimental protocol. Conclusion: Ingestion of blood orange juice modulates miRNA expression in PBMC and plasma and decreases the protein content of NF-&kappa;B in PBMC, without changing caloric intake, anthropometric parameters, and metabolic biomarkers evaluated. (AU)

• FAPESP's process: 18/25046-7 - Chronic effect of blood orange juice intake on microRNA expression profile and inflammatory response in overweight women
• Grantee: Vinícius Cooper Capetini
• Support Opportunities: Scholarships in Brazil - Doctorate