Therapeutic potential of supplementation with bergamot fruit extract (Citrus bergamia) in the prevention of obesity-induced cardiac dysfunction: relationship with inflammatory mediators, oxidative stress and the participation of biogenic amines

• Grant number: 22/01925-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): November 01, 2022
• Effective date (End): February 29, 2024
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Camila Renata Corrêa
• Grantee: Matheus Antônio Filiol Belin
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Obesity is defined as the excessive accumulation of body fat that can lead to health damage, including cardiac dysfunction. Oxidative stress and inflammation, originating from adipose tissue dysfunction, in the obesogenic scenario, are some mechanisms involved in this pathophysiology. Bioactive compounds present in vegetables, due to their antioxidant and anti-inflammatory properties, contribute both to therapies and to the treatment of cardiovascular diseases. Bergamot (Citrus bergamia) is a citrus fruit, with antioxidant and anti-inflammatory action, which demonstrates a beneficial effect on metabolic parameters due to phenolic compounds. However, there are other compounds in this fruit that have not yet been evaluated in the obesity model and that may be involved in this process, such as biogenic amines (ABs). ABs are substances with aliphatic organic bases belonging to bioactive or biologically active amines that perform metabolic functions in the body, in addition to antioxidant and anti-inflammatory activity. Among ABs, the literature reports that serotonin and dopamine are involved in the modulation of appetite and food intake, and may, consequently, be related to obesity. The objective of this work will be to verify the role of bergamot fruit extract supplementation on inflammatory mediators, oxidative stress, and the profile of biogenic amines in the myocardium of obese rats. Wistar rats will form four experimental groups (n = 15 animals/group). Group G1 will receive control diet plus placebo (CD + P), G2 control diet + bergamot fruit extract (CD+Ex), G3 diet high in sugar and fat (HSF) (HSF + P), and G4 diet HSF plus extract of bergamot fruit (HSF+Ex) for 20 weeks. The extract and placebo (water) will be administered by gavage (250mg/Kg). The nutritional profile (caloric intake, body weight, adiposity index), cardiac dysfunction by Doppler echocardiographic assessment, obesity complications (biochemical tests, plasma hormones, insulin resistance (HOMA-IR), and systemic blood pressure will be measured. In the myocardium, the transcriptional factors NRF-2 and NFk-B will be determined by western blotting, inflammatory mediators (IL-6 and TNF-±. IL-10, IL-1Ra) by the ELISA technique, indicators of oxidative stress (malondialdehyde, 4 -hydroxynonenal and protein carbonylation), and detection of the profile of biogenic amines, which will also be determined in the bergamot fruit extract, by high-performance liquid chromatography (HPLC). The data will be presented by descriptive measures of position and variability and analyzed by specific comparison tests according to their behavior.