Title: The effects of semaglutide on adolescent mice
Supervisor: Dr. David Wright
Committee members: Dr. Cameron Mitchell, Dr. Daniel Gamu
Abstract:
Background: GLP1 receptor agonists (GLP-1ra) have previously been used for the treatment of Type 2 Diabetes. Human trials have shown body weight loss of ~ 15-20% in adults and ~ 5-15% in adolescents with semaglutide, a weekly injectable GLP-1ra, primarily facilitated by reductions in food intake. Semaglutide causes large reductions in adipose and lean tissue mass in adults, but there is limited information on its effects in adolescent populations.
Purpose: The aim of my thesis is to assess the effects of semaglutide on visceral, muscular, and skeletal tissues in adolescent male and female mice. I hypothesize that semaglutide will attenuate weight gain by reducing food intake. I also hypothesize that adiposity, muscle mass, strength, and bone mass will be reduced.
Methods: Adolescent male and female C57BL6/J mice will be weaned at 4 weeks old and placed on a high fat diet for ~4 weeks (HFD, 60% fat, 20% carbohydrate, 20% protein). Mice will be assigned to sex and weight-matched groups: 1) HFD, 2) HFD + Semaglutide. Mice will then be subcutaneously injected daily, for 3 weeks, at the start of dark phase with 10nm/kg semaglutide or vehicle solution, with food intake and body weight measured daily. During the 4th week of treatment, an oral glucose tolerance test, in vivo body composition analysis, grip strength testing, and tissue collection will occur.
Significance: The characterization of body compositional changes and the functional implications of semaglutide treatment in an adolescent murine diet-induced obesity model has yet to be described. Elaboration on semaglutide’s multi-tissue effects is pertinent to the rise in prescriptions for both adults and adolescents.