Efeito do consumo crônico do adoçante artificial sacarina sobre parâmetros metabólicos e atividade mitocondrial do tecido adiposo branco de camundongos hiperalimentados durante a lactação

Abstract

Obesity, defined by the excessive accumulation of body fat correlated with an increased risk of morbidity and mortality, has become a pandemic in recent decades. In parallel, the use of non-caloric sweeteners (NCS) as a weight control strategy has steadily grown. However, recent studies have revealed that NCS are not inert compounds and may be associated with increased adiposity and the promotion of metabolic changes. Saccharin, one of the most widely consumed artificial sweeteners in the world, has been the subject of extensive debate regarding its safety. This is due to its ability to activate sweet taste receptors (T1R2/T1R3) present in various organs, including white adipose tissue (WAT), influencing the process of adipogenesis. The literature suggests that its consumption may be correlated with effects on gut microbiota, glucose tolerance, hyperinsulinemia, increased food intake, and body weight gain. However, there is little understanding of its effects on molecular mechanisms and mitochondrial energy metabolism in adipocytes. Therefore, the present study aimed to evaluate the specific impact of saccharin consumption on endocrine-metabolic parameters and mitochondrial function of epididymal white adipose tissue (EWAT) in mice. To induce obesity, we applied the litter reduction method (LR), in which litters were reduced to 3 male pups per dam on the 3rd day of life. At 90 days of life, the groups were subdivided into: control and obese groups that received water containing 0.3% saccharin (C-SA and O-SA) for 3 months and control and obese groups that received only water (C-AG and O-AG). The animals sought sweeteners more than water, suggesting an addictive effect. The deleterious effects of saccharin were mainly observed in the control group, which showed an increase in body weight, body fat percentage, EWAT hyperplasia, and a decrease in gene expression of Acetyl-CoA, ChREBP, PPARα, FASn, and carbohydrate oxidation. In obese animals, saccharin consumption was associated with increased lipid peroxidation in EWAT and decreased oxidation of fatty acids and carbohydrates, as well as a reduction in gene expression of FABP4, SREBP-1, PPARγ, and LPL, despite improving glucose response in the tolerance test. We propose that saccharin acts on body adiposity by influencing energy metabolism and glucose tolerance regulation differently depending on the animal's nutritional status. Its high consumption presents a potential risk, particularly for eutrophic animals, contributing to increased adiposity in this group, and its excessive use should be discouraged, especially for weight loss purposes.