A high-fat diet induced NMRI mouse model of metabolic syndrome: focus on brain-derived neurotrophic factor (BDNF)

Abstract

The association of brain-derived neurotrophic factor (BDNF) as a member of neurotrophin family and metabolic syndrome (MetS) has been proposed, however basic evidence necessary to prove (or disprove) this association in non-genetic animal model is rare. Therefore, we investigated the alteration of encephalic BDNF gene expression in a mouse model of high-fat diet (HFD) induced MetS. To translate MetS, male NMRI mice (9 weeks old; N = 13) fed on a HFD including suet powder (37.50%) and granulated sugar (19.85%) while control mice were fed a diet contained suet powder (6.25%) and granulated sugar (49.09%). We monitored the development of MetS by measuring fasting blood sugar (FBS) and lipid (total cholesterol (TC) and triacylglycerol (TGs)) and lipoprotein (high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C)) profiles, atherogenic index (AI), and somatic indices after 1 and 3 months of dietary interventions. The HFD intake led to increased body weight, liver weight, FBS, TC, and decreased HDL-C as compared to chow diet in mice after first month of dietary intervention. The increased FBS, body weight, abdominal fat mass, TGs, TC, and VLDL-C and decreased HDL-C were observed in HFD-fed mice as compared to those of chow-fed mice at 3th month. The statistical comparison of two HFD groups in two time intervals of 1st and 3th month confirmed that our HFD-induced MetS model was reliable because FBS, TGs and VLDL-C, TC, and AI have been increased significantly during selected time intervals. The AI increased significantly in HFD-fed mice compared to chow-fed mice after 3 months. The AI in HFD-fed mice treated with HFD for 3 months was increased significantly as compared to mice fed HFD for 1 month. Our diet-induced model more closely mimics the changes observed in human MetS and showed that encephalic BDNF gene in mice fed HFD was under-expressed by 0.30 fold with respect to chow-fed mice after 3 months of dietary intervention.

Keywords: Atherogenesis; BDNF; High-fat diet; Lipoprotein; Metabolic syndrome.