Functional and molecular analysis of energy metabolism from mice exposed to artificial light at night and fed or not to low-protein diet

Author(s)

Patricia Cristine Borck

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2017-12-06

Examining board members

Everardo Magalhães Carneiro; José Cipolla Neto; Gabriel Forato Anhê; Sabrina Grassiolli; Andre Schwambach Vieira

• Advisor: Everardo Magalhães Carneiro; Elaine Vieira

Abstract

The use of electric light, as well as, the exposure to irregular light schedules has become common over the 20th century and coincides with increased global prevalence of obesity and metabolic diseases. Several studies have reported that exposure to artificial light at night (ALAN) leads to disruption of circadian rhythm and predispose to obesity and metabolic disorders. Dietary protein restriction, in utero and at early life, leads to altered circadian system. Furthermore, reduced protein on diet at gestation exacerbates the metabolic changes induced by HFD and predisposes to obesity and metabolic syndrome at adulthood. However, remains unclear which mechanisms underlie the metabolic changes induced by exposure to ALAN and, whether protein restriction, after weaning, could exacerbates the deleterious effects induced by nighttime light exposure, and predispose to obesity and metabolic disorders. First we found that mice exposed to ALAN, during 8 weeks, exhibited increased body and fat pad weights, as well as peripheral insulin resistance. Furthermore, these mice developed hepatic steatosis, which could be explained by decreasing expression of the clock gene Rev-erbalpha and consequent up-regulation of it lipogenic targets ACL and FAS. Mice exposed to ALAN also exhibited increased expression of Rev-erbalpha-targeting microRNAs (miRNAs) miR-140-5p, 185-5p, 326-5p and 328-5p, in liver. Besides, in primary hepatocyte culture, the exogenous expression of these miRNAs down-regulated the expression of Rev-erbalpha at gene and protein level. However only the miR-140-5p and miR-185-5p directly bind in the Rev-erbalpha 3¿UTR region. Taken together, these evidences indicate that exposure to ALAN could leads to hepatic steatosis through increasing the expression of miRNAs, which coordinate the down-regulation of Rev-erbalpha expression. Next we observed that mice fed to low-protein (LP) diet during 14 weeks and exposed to ALAN (LL) during the last 8 weeks, exhibited some metabolic changes similar than mice fed to normal protein (NP) diet including, increased body weight, as well as increased fasting and fed glycemia, which was followed by glucose intolerance and up-regulation of Pck1 at subjective day. On the other hand LP/LL group also showed specific metabolic changes, as reduced peripheral insulin sensitivity at subjective day and lost of daily variation in Pck1 expression. Also, these mice did not exhibit altered timing of energy intake toward the subjective day. Thus, our results suggest that protein restriction modify some of the metabolic alteration promoted by nighttime light exposure instead of exacerbates the deleterious effects induced by this condition (AU)

• FAPESP's process: 13/26740-0 - Molecular and functional analysis of the mechanism of secretion and insulin action in malnourished mice subjected to continuous exposure to light
• Grantee: Patricia Cristine Borck
• Support Opportunities: Scholarships in Brazil - Doctorate