Efeito do tratamento antiobesidade com Citrus aurantium ou sinefrina sobre o metabolismo de hormônios tireoidianos camundongos adolescentes obesos no modelo de programação por redução do tamanho da ninhada

Abstract

Obesity is a complex and chronic disease, now recognized as a global epidemic. Its escalating prevalence is attributed to factors such as lifestyle changes, genetic influences, and notably, early-life epigenetic factors like postnatal overfeeding, which predisposes individuals to obesity and associated disorders. The pursuit of effective obesity treatments has led to a focus on herbal medicine, such as the use of Citrus aurantium L., belonging to the Citrus genus (Rutaceae). The extract from the immature fruit peel contains adrenergic amines, with synephrine being the primary active component known for its adrenergic and lipolytic properties. Recent findings revealed that Citrus aurantium L. improved the metabolic profile of mice programmed for overfeeding but concurrently elevated thyroid hormone concentrations. In this pioneering study, we investigated the impact of treatment with Citrus aurantium L. and/or synephrine on thyroid metabolism and its repercussions on the heart in obese adolescent mice programmed through early postnatal overfeeding. Three days after birth, male Swiss mice were divided into two groups: an overfed group (SL) with a litter reduced to 3 pups to induce postnatal overfeeding and a control group (NL) with a litter of 9 pups. At 30 days of age, SL and NL mice were subjected to a 19-day treatment with Citrus aurantium L., standardized at 6% synephrine (SL-C6%) or 30% synephrine (SL-C30%), isolated synephrine (SL-Syn), or vehicle (NL). The results indicate a correlation between the anti-obesity effect of Citrus Aurantium L. or synephrine and thyroid function, manifested through increased serum levels of T3 (SL-CA6%, +84.03%; SL-CA30%, +105.19%, and SL-Syn +136.5%) and T4 (SL, +201.89%; SL-CA6%, +344.90%; SL-CA30%, +335.36%, and SL-Syn, +453.92%), along with enhanced TAM functionality due to increased TRHα receptor expression. Although there was no reduction in body weight, the treatment effectively curtailed body mass gain and adiposity during the treatment period (SL-CA6%, -21.49%; SL-CA30%, -21.58%, and SL-Syn, -21.67%). While there were no discernible differences in the heart rate of treated animals, isolated synephrine led to a notable increase (+156.07%) in the expression of the α-MHC gene, associated with adverse effects on the heart. In the other treated groups, the likely synergistic effect of other components of C. aurantium L. may have mitigated the development of this synephrine-induced effect on the heart.