Impacto do jejum intermitente no hipotálamo de camundongos obesos induzidos por dieta

Abstract

Continued consumption of high-fat foods leads to obesity and peripheral and central metabolic changes. We aimed to investigate how intermittent fasting (IF) could influence the hypothalamus of mice fed a high-lipid diet, focusing on molecular markers related to the hunger-satiety function in the arcuate nucleus (ARC) region of the hypothalamus. Also, food and energy intake, body mass, and resistance to leptin were studied. Male C57BL/6J mice, aged three months, were divided into a control group (C, fed a control diet) and a high-fat group (HF, fed a diet rich in lipids) for eight weeks. An additional four weeks, half of the animals in each group did IF (24h fed/24h fasting), while the other half of the animals continued to feed freely. Thus, four new groups were formed: C, CIF, HF, and HFIF. Body mass and energy consumption increased in HF animals, as well as fatty pads, and there was an increase in blood glucose, total cholesterol, triacylglycerol, insulinemia, insulin resistance index (FIRi), leptinemia and reduction in adiponectinemia. Leptin gene expression increased in the epididymal adipose tissue in the HF group. The IF reduced all these parameters. In the hypothalamus, gene expressions were increased for Leptin and Socs3, with a decrease in Obrb, suggesting resistance to leptin. The IF significantly improved these parameters, even though it was not statistically significant for Socs3. The gene expression of Npy was higher in the HF and HFIF groups, while Pomc decreased predominantly in HF. The protein expression of NPY was higher in the groups submitted to IF. POMC showed a significant reduction in HF, but there was an increase in HFIF. Immunofluorescence with NPY and POMC labeling in the ARC region in the hypothalamus confirmed the molecular results. Gene expression of inflammatory markers Il-6, Il-1 and Tnf- in the hypothalamus were higher in the IF groups, except for Tnf- in the HFIF group. In conclusion, there is a beneficial effect of IF in diet-induced obese mice reduced body mass, improved lipid metabolism, and sensitivity to peripheral insulin, leptin, and adiponectin. The IF reduced the central resistance to leptin, increasing the expression of hypothalamic Obrb. However, there was an increase in the hypothalamic expression of pro-inflammatory markers, indicating that IF may have a side effect, at least in the period used in this study, which should be considered in the treatment of comorbidities associated with diet-induced obesity.