title: Effects of liraglutide in hypothalamic arcuate nucleus of obese mice.
abstract: OBJECTIVE
  The neuroprotective effects of liraglutide (200 μg/kg, twice daily, subcutaneous administration) in the hypothalamic arcuate nucleus (ARC) of diet-induced obese mice were investigated.
  
  
  METHODS
  C57BL/6 mice were separated into groups: standard chow treated with vehicle or liraglutide and the respective liraglutide pair-fed group; high-fat diet treated with vehicle or liraglutide and the respective pair-fed group. Body mass (BM) evolution, carbohydrate metabolism, leptin resistance, proteins involved in energetic balance, apoptosis, and microglia in the ARC were studied.
  
  
  RESULTS
  Obese animals showed glucose intolerance, resistance to insulin and to anorexigenic effect of leptin, and microgliosis accompanied by elevated Bax/Bcl2 ratio in the ARC. Liraglutide improved the carbohydrate metabolism, BM loss, and the activation of pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) in the ARC. The liraglutide enhanced leptin sensitivity and diminished the microgliosis with decrease in Bax/Bcl2 ratio.
  
  
  CONCLUSIONS
  Liraglutide activates central anorexigenic pathways, thereby diminishing the energy intake of obese mice and improving the metabolic parameters related to obesity. Liraglutide is a relevant neuroprotective agent, which can decrease the microgliosis and stimulate the anti-apoptotic pathway, a significant effect in the treatment of obesity and its comorbidities. Some benefits of liraglutide are independent of the BM loss, which usually accompanies the drug administration.
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio De Janeiro, Rio De Janeiro, Brazil.
authors.forename: Andre R C
authors.initials: AR
authors.lastname: Barreto-Vianna
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio De Janeiro, Rio De Janeiro, Brazil.
authors.forename: Marcia B
authors.initials: MB
authors.lastname: Aguila
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio De Janeiro, Rio De Janeiro, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D002149:Energy Intake; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D000069450:Liraglutide