Jejum intermitente em camundongos alimentados com dieta hiperlipídica ou dieta rica em frutose: analise do fígado, ilhota pancreática e tecido adiposo branco

Abstract

Objective: The study aimed to evaluate the effects on intermittent fasting (IF) on the liver (structure, steatosis, and metabolism), the pancreas (mass of beta cells, molecular markers), and subcutaneous white adipose tissue (WATs, beige adipocyte formation and thermogenic gene expression). Methodology: Male C57BL / 6 mice, aged three months, were fed control diet (C, 10% Kcal fat), high-fat diet (HF, 50% Kcal fat) or diet high in fructose (HFr, 50% Kcal fructose) for eight weeks. Then, half of each group was submitted to IF for an additional four weeks (feeding 24 h / fasting 24 h), forming six groups: C, C-IF, HF, HF-IF, HFr and HFr-IF. Results: The HF and HFr groups presented hyperglycemia, hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, increased hepatic steatosis, and pancreatic islet hypertrophy with increased alpha and beta-cell mass, as well as adipocyte hypertrophy of WATs. Food intake on the day fed in groups with fast were not different between groups, but HF-IF and HFr-IF groups had a reduction in body mass, total cholesterol and triacylglycerol. The oral glucose tolerance test and insulinemia improved in the IF, regardless of the diet consumed, as well as decreased liver lipogenesis and increased beta-oxidation, resulting in reduced hepatic steatosis and inflammation. Insulin resistance increased in the HF group and was reduced in the HF-IF group. There was a decrease in the p-AKT / AKT (protein kinase B) ratio in the HF group, and IF increased this ratio in the HF-IF group. The p53 tumor suppressor increased in the HF group and IF decreased it in the HF-IF group. The IF led to a reduction in the size of the pancreatic islets and the mass of alpha and beta cells, in addition to improving insulin signaling and decreasing apoptosis. There was browning in WATs in the HF-IF animals and increased respiratory quotient (RQ) on the fed day. UCP (uncoupled protein) 1 increased in the groups with IF, which also decreased inflammatory markers and pro-apoptotic markers in the adipocytes of WATs. Conclusions: IF improved the metabolism of carbohydrates and hepatic pro-inflammatory markers, in addition to regulating the mass of alpha and beta cells and improving insulin signaling with decreased apoptosis, even with continued intake of the HF diet. The IF also promotes browning in WATs adipocytes, acting on thermogenesis and the adipoinsular axis, with improved response to leptin, insulin, and inflammatory markers