Matheus Antonio Filiol Belin, Jordanna Cruzeiro, Aline Nunes, Lucas Fazardo de Lima, Luis Eduardo Sormani, Cristina Schmitt Gregolin, Murilo Dalarme Tanganini, Taynara Aparecida Vieira, Núbia Alves Grandini, Juliana Silva Siqueira, Thiago Luiz Novaga Palacio, Anderson Seiji Soares Fujimori, Dijon Henrique Salomé de Campos, Silmeia Garcia Zanati Bazan, Igor Otávio Minatel, Gustavo Henrique Rodrigues da Silva, Silvana Aparecida Rocco, Giancarlo Aldini, Mauricio Luis Sforca, Marcelo Maraschin, Giuseppina Pace Pereira Lima, Camila Renata Correa
Obesity promotes cardiac remodeling and dysfunction through oxidative stress, inflammation, and metabolic disturbances. Citrus bergamia (bergamot) has shown beneficial effects on obesity-related cardiometabolic risk factors, but its cardiac effects remain unclear. We evaluated bergamot supplementation in a rat model of diet-induced obesity using integrated assessments of cardiac structure and function, redox and inflammatory status, biogenic amines, fatty acids, and metabolites. Wistar rats (n=54) were randomized to Control, Obese, or Obese+Bergamot groups for 20 weeks; bergamot was administered by gavage at 250 mg/kg/day. Animals in both obese groups had higher body weight (p<0.01) and adiposity index (p<0.0001) than controls, confirming diet-induced obesity. Untreated obese rats also exhibited higher systolic blood pressure, cardiac remodeling, oxidative damage, higher cardiac TNF-α and IL-10 concentrations, and reduced NRF2 expression (p<0.05). Bergamot attenuated cardiac remodeling, preserved systolic and diastolic function (p<0.05), reduced malondialdehyde (p<0.05), protein carbonyls (p<0.0001), and cardiac TNF-α and IL-10 concentrations (p<0.05), and increased ferric reducing antioxidant power (p<0.01). Exploratory cardiac metabolic profiling showed partial recovery of putrescine and spermidine, higher spermine and histamine concentrations (p<0.05), lower serotonin monoforms (p<0.05), higher arachidonic acid abundance (C20:4n6; p<0.05), and higher inosine abundance (p<0.05) following bergamot supplementation. Bergamot-associated cardiac preservation occurred despite persistent obesity and without restoration of NRF2 expression, the NRF2/KEAP1 ratio, or myocardial NAD+ and NADP+ concentrations. Changes in polyamine, fatty acid, and purine-related profiles, including higher spermine and inosine, identify candidate metabolic features associated with this response but do not establish these metabolites as causal mediators.