Avaliação da plasticidade do tecido adiposo em camundongos magros ou moderadamente obesos submetidos ao jejum e realimentação

Abstract

INTRODUCTION: Evidence has shown that fasting may be a strategy for reducing adiposity. However, few studies have investigated the biology of adipose tissue after fasting and refeeding. AIM: To evaluate the effect of refeeding after fasting on the remodeling and inflammation of adipose tissue in lean and mildly obese mice. METHODS: BALB/c male mice were divided into two experimental groups and fed for 8 weeks with a standard diet (LABINA, lean) or a diet high in refined carbohydrates (HC, mildly obese). During the twentieth week of life, they were subjected to fasting protocols for 3h, 24h or 48h. Mice subjected to 48h of fasting were subsequently refed for 24h on a standard or HC diet. The mice were anesthetized and euthanized. Serum and liver, epididymal, retroperitoneal, mesenteric, inguinal, and brown adipose tissues were collected. Serum biochemical parameters, adipose tissue weight, and histomorphological analyses of the different tissues were performed. mRNA was isolated from epididymal and inguinal tissues, and the expression of lipolytic, lipogenic, and inflammatory genes was evaluated using qPCR. RESULTS: Mice fed the HC diet were mildly obese, that is, they showed increased adiposity without weight change. Additionally, they presented alterations in glucose and lipid metabolism, basal increases in lipolysis, adipokines, and inflammatory mediators in epididymal and inguinal adipose tissue. In both lean and mildly obese mice, a 24-hour fast was insufficient to reduce adiposity. With the prolongation of fasting to 48 h, lean mice showed a reduction in adiposity accompanied by an increase in interstitial fibrosis, expression of lipolytic genes, and inflammatory cytokines in epididymal and inguinal adipose tissues. In contrast, mildly obese mice were not responsive to adiposity loss, with no change in the expression of lipolytic genes and inflammatory cytokines in the adipose tissue. In liver analyses, after 48-hour fasting, hepatic concentrations of triglycerides and cholesterol, as well as the amount of macrovesicular droplets, were increased in lean mice. In contrast, although mildly obese mice did not show alterations in triglyceride and cholesterol concentrations, there was an increase in microvesicular droplets (<65 μm²) after prolonged fasting, which persisted during the refeeding period. After a 24-hour refeeding period with a standard diet, lean mice returned to baseline values of body adiposity. Mildly obese mice fed the HC diet showed an increase in systemic inflammation, characterized by an increase in leukocyte, lymphocyte, granulocyte, and pentraxin 3 concentrations. However, when mildly obese mice were fed a standard diet, there was an attenuation of this systemic inflammation. CONCLUSION: Mildly obese mice are resistant to adiposity loss under fasting stimulus, characterized by a state of inflammatory inflexibility, marked by failure in lipolysis and increased inflammatory mediators in adipose tissue. When these animals were fed a standard diet, there was no difference in visceral or subcutaneous adiposity. In contrast, when re-fed with an HC diet, they presented with increased systemic inflammation. Therefore, a "healthy" dietary pattern in re-feeding after fasting, regardless of weight loss, was important to prevent postprandial inflammation, which is caused by re-feeding with an unhealthy diet, i.e., rich in refined carbohydrates.