Investigation into the effects of chronic social stress on the regulation of feeding and metabolism in mice

  • Simone Carneiro Nascimento

Student thesis: Doctoral Thesis

Abstract

Stress is known to affect energy metabolism in humans and animals. This thesis aimed to investigate the effects of chronic social stress (CSS) on energy expenditure (EE), respiratory exchange ratio (RER), neuroendocrine regulators of feeding and the serotonergic system. Adult male C57BL/6 mice were exposed to 15 days of social stress or control handling. In an iterative series of experiments, food intake (FI) and body weight (BW) were measured daily, indirect calorimetry was evaluated before and after the CSS period, and glucose homeostasis was evaluated using a glucose tolerance test. At termination, plasma and adipose tissues were collected for determination of ghrelin, leptin and insulin concentrations, as well as gene expression of leptin and leptin receptor. In discrete brain areas, ghrelin receptor (Ghs-r1a) immunopositive cell count, gene expression of ghrelin and leptin receptors, as well as serotonin 5-HT1A, 5-HT2A and 5-HT2C receptor binding (by means of autoradiography) and gene expression, were analysed.
The present results are consistent with CSS leading to a reduced conversion of FI into an increased BW, as demonstrated by an increased FI with an absence of BW effect or by unaffected FI with an attenuated BW increase. Increased RER was observed in CSS mice, indicating a greater carbohydrate utilisation as fuel source. This study also identified markers of increased hunger signalling i.e. increased plasma ghrelin and ventromedial hypothalamic Ghs-r1a mRNA expression, and decreased satiety signalling i.e. decreased plasma leptin and WAT Lep mRNA expression. The lower leptin levels were consistent with an increase in energy demand, as also suggested by decreased insulin levels. CSS affected the serotonergic system through modifications of the binding activity and gene expression of serotonin receptors, and by modification of serotonin transporter gene expression.
In conclusion, the present thesis demonstrated that CSS in mice leads to both central and peripheral changes consistent with increased energetic requirements, which has important implications for brain function.
Date of Award15 Apr 2019
Original languageEnglish
Awarding Institution
  • University of Roehampton
SponsorsNational Council for Scientific and Technological Development (CNPq) - Science without Borders & Swiss National Science Foundation
SupervisorJolanta Opacka Juffry (Supervisor), Michael Patterson (Supervisor) & Christopher Pryce (Supervisor)

Keywords

  • Chronic social stress
  • Brain
  • Depression
  • Energy metabolism
  • Energy homeostasis
  • Feeding behaviour
  • Calorie efficiency
  • Ghrelin
  • Leptin
  • Insulin
  • Serotonin

Cite this

Investigation into the effects of chronic social stress on the regulation of feeding and metabolism in mice
Carneiro Nascimento, S. (Author). 15 Apr 2019

Student thesis: Doctoral Thesis