Efeito hipotalâmico do jejum intermitente em camundongos alimentados com frutose

Abstract

We are currently exposed to foods high fructose, leading to an increasing number of metabolic disorders, such as hyperleptinemia. Leptin regulates food intake by acting on the hypothalamus. On the other hand, there is a continuous search for a healthier life. Thus, the objective of the work was to study the effects of intermittent fasting (IF) on the signaling of leptin and neurotransmitters that control appetite/satiety and hypothalamic inflammation in mice fed a high fructose diet, as an alternative to the problems caused by this diet, since the IF can improve the health of people with chronic diseases by modulating metabolic and functional risk factors. C57BL / 6 male mice at 12 weeks of age were divided into two groups, control (C, control diet) and high in fructose (HFru, high fructose), for 8 weeks. After this period, the animals were divided into 4 groups, those that received ad libitum food and those that did JI (24h fed / 24h fasting): control (C), high fructose (HFru), C-JI (control- IF) and HFru-IF (high fructose-IF) for 4 weeks, totaling 12 weeks of experiment, when the animals were euthanized. Fructose intake was able to increase total cholesterol, triacylglycerol, glycemia, insulin, Fasting Insulin Resistance Index (FiRi), leptin and reduce plasma adiponectin, while JI reduced the animals' body mass (BM) and improved all parameters cited. Despite the IF protocol and weight loss, there was no difference in the food and energy consumption of the groups. The inflammatory markers had their hypothalamic gene expression increased afterwards in the C-IF group. IF, as well as fructose increased the expression of hypothalamic Leptin and also the expression of Obrb and Socs3 in the groups C-IF and HFru, however there was a decrease in the expression of these markers (Obrb and Socs3) in the group HFru-IF. An increase in Npy and Pomc gene expression was observed in the HFru-IF group and a reduction in Pomc in the HFru and C-IF groups. In immunofluorescence, an intense green mark was observed around the third ventricle that indicated the presence of NPY, being more pronounced in animals submitted to IF, while for POMC, a less intense green mark was detected in the groups, mainly in the HFru and HFru-IF- groups. In conclusion, IF was able to decrease BM throughout the study and benefit lipid, glycemic metabolism and sensitivity to insulin, adiponectin and plasma leptin. However, there was an increase in hypothalamic inflammatory markers in mice submitted to IF, which, in the long run, can lead to an imbalance in the body's energy balance and food intake. In addition, IF led to an increase in hypothalamic leptin with probable leptin resistance. Therefore, we cannot yet say with certainty that IF can be used as a non-pharmacological treatment for metabolic diseases.