Alterations in glucidic metabolism and behaviour induced by high-fat diet in C57Bl/6J male mice. Effects of chronical mild stress and pharmacological treatment with Metformin or Fluoxetin

ANDRES PROCHNIK; MARIA ROSA GONZALEZ MURANO; MARÍA PAULA MARCONE; MIRIAM RUTH WALD; ANA MARIA GENARO

Mar del Plata

Congreso; Reunión Anual de Sociedades Biocientíficas SAIC, SAFE, SAB, SAP, AACyTAL, NANOMED, HCS; 2019

SAIC, SAFE, SAB, SAP, AACyTAL, NANOMED, HCS

ALTERATIONS IN GLUCIDIC METABOLISM AND BEHAVIOUR INDUCED BY A HIGH-FAT DIET IN C57BL/6J MALE MICE. EFFECTS OF CHRONIC MILD STRESS AND PHARMACOLOGICAL TREATMENT WITH METFORMIN OR FLUOXETIN. Andrés Prochnik, María Rosa González Murano, María Paula Marcone, Miriam Ruth Wald. Ana María GenaroWe previously studied in mice the effects of a high-fat diet (HFD) and chronic mild stress (CMS) in the development of cognitive impairment and metabolic dysregulation. HFD caused both hyperglycemia and glucose intolerance while CMS only caused the latter. Both treatments reduced spatial and working memory, yet no synergy had been observed between them. Metformin (MET) is a medicament for type 2 diabetes and Fluoxetin (FLX) is a drug used as treatment for stress-related symptoms. The objective of this research is to analyze the effects of MET and FLX in the way how HFD and CMS develop metabolic and conductual alterations. 4 weeks-old mice were fed with standard diet (SD) or HFD. 8 weeks later, groups were subdivided and exposed to CMS. Some received either FLX or MET in drinking water in doses of 15 mg/kg*day and 250 mg/kg*day, respectively. FLX treatment began concurrently with CMS, while MET was administrated 4 weeks after CMS initiation. These treatments lasted until the subjects were 32 weeks-old. Behaviour and metabolic tests were performed during the final weeks of treatment. Our results show that MET had no effect on glucidic metabolism, and while mice under HFD+CMS had glucose intolerance (p0.05). Concerning behaviour, HFD and HFD+CMS reduced working memory in the Y-maze test compared to SD (HFD p=0.02;HFD+CMS p=0.04). MET reverted these effects, and FLX corrected behaviour only if CMS was present (HFD+FLX vs SD p