Efeitos metabólicos distintos decorrentes da modificação dietética e do jejum intermitente no tratamento da obesidade

Abstract

Introduction: Obesity is characterized by substantial fat accumulation and is known to be associated with several systemic metabolic disorders. Furthermore, obesity has been reported to induce changes at the cellular level, modifying the structure of central metabolic organelles, such as mitochondria and rough endoplasmic reticulum (ER). In this regard, although the primary treatment of obesity aims at weight loss, it is still unclear whether the loss of adiposity is capable of reversing changes in the subcellular structure in different metabolic tissues, especially mitochondrial and ER architecture, or whether there are differences between different dietary treatments, which may affect whole-body metabolic response. Thus, the present study aims to compare the effect of different dietary treatments in reversing the obesity’s systemic phenotype as well as mitochondrial ultrastructure and ER dysfunction. Methods: Eight-week- old male C57BL6/J mice were fed a standard or high-fat (HF) diet to induce obesity (Ob). After approximately 12 weeks, Ob animals were allocated into two groups for dietary treatment: (i) diet shift to a standard diet (Ob-S) or (ii) maintenance of a HF diet alternated in an intermittent fasting (Ob-IF) for 5 weeks. Metabolic parameters, mitochondrial and ER ultrastructure as well as mitochondria-ER interaction in the liver and subcutaneous adipose tissue (IAT) were evaluated by transmission electron microscopy (TEM). Results: Although both treatments induced weight loss and adiposity, these effects were more pronounced in Ob-S animals compared to Ob- IF animals, associated with more significant changes in glucose and lipid metabolism. Indeed, diet shift enhanced hepatic steatosis and insulin sensitivity-related parameters. Tissue- specific analyses of mitochondrial ultrastructure showed an increase in the number of hepatic mitochondria in Ob-S animals compared to Ob animals, indicating a possible occurrence of mitochondrial biogenesis, in addition to changes in ER morphology and qualitative restoration of the failure in mitochondria-ER interaction induced by obesity. In IAT, in turn, both treatments were effective in restoring density and decreasing the number of mitochondria in adipocytes, a process suggestive of induction of mitochondrial fusion. In particular, IF also induced an increase in mitochondrial area and a decrease in mitochondrial circularity, which further supports the idea of mitochondrial fusion after treatment. Conclusion: Obesity dietary treatment from an unhealthy to a healthy diet is more effective than intermittent fasting, although both treatments induce similar reduced food intake. Furthermore, modulation in mitochondrial plasticity seems to be specific depending on the tissue evaluated, which might reflect in better metabolic outcomes presented by each of the dietary treatments.