VGF and Type II Diabetes: Decrease of VGF fragment levels in adipose tissues of diet-induced obese mice

VGF encodes a precursor protein processed in various neuropeptides, one of these involved in metabolic mechanisms and named TLQP-21, stimulates the autonomic activation of adipose tissue and reduces the early phase of diet-induced obesity in mouse. In immunohistochemistry (ICC) and ELISA, we used antisera to short sequences at C-/N-terminus of the VGF precursor, and of several VGF-derived peptides. Plasma of type II diabetes (DMII) was taken from patients with different body mass index (BMI): (i) BMI =18-24, (ii) BMI=25-29, (iii) BMI=30-39, in parallel with samples from healthy subjects (iiii) matched with BMI of group “i” (n=10 samples/ group). Male CD1 mice were fed with standard chow (group-a: controls), or with standard chow plus 36% lard (group-b: obese) for 16 weeks (n=24 animals/group). For glucose tolerance test, 12 mice from groups a and b, respectively, received i.p. injection of glucose (3g/kg), and were sacrificed after 120 minutes. White and brown adipose tissues (WAT and BAT, respectively) were extracted (n=9 animals/group) while for ICC, mice (~4/group) were perfused with 4% paraformaldehyde. In plasma of DM II patients, we found a clear decrease of VGF C-t, in parallel with the increase of BMI (iiii=1200±70, i=1100±85, ii=760±60, iii=550±40 pmol/ml, mean±SEM). In WAT, through ELISA, we found a significant decrease for VGF C-t in group-b respect to group-a (2±0.5 vs. 5±2*, pmol/g, mean±SEM, *p<0.03). A similar trend was observed in BAT, not only for VGF C-t, but also for N-t, TLQP, and RVW peptides (groups b vs. a, respectively: 10±3 vs. 22±7**, 9±3 vs. 18±4**, 210±75 vs. 420±95**, and 38±11 vs. 70±10*, pmol/g, means±SEM, *p<0.007,**p<0.02). Moreover, exclusively in BAT of group-a but not of group-b, we measured a great increase of VGF C-t, N-t and RVW peptide levels after glucose load (values taken before and after glucose load, respectively: 22±7 vs 35±5**, 18±4 vs. 30±7 **and 70±10 vs. 95±10*, pmol/g, means±SEM, *p<0.02,**p