Neuroanatomy of energy and glucose regulation: the novel TLQP-21 and TLQP-62 peptides

TLQP-21 and TLQP-62, two peptides encoded by the VGF (non-acronymic) gene product, are expressed in specific endocrine cells and neuronal systems, including nor-adrenergic fibres in white and brown adipose tissue (WAT and BAT, respectively), and gastric, adrenal and hypophyseal endocrine cells. Interestingly, central infusion of TLQP-21 reduced food intake and body weight in “obese” Siberian hamster, while increasing energy expenditure in mouse. At the same time, peripheral injection studies showed little success. The same TLQP-21 peptide was recently shown to oppose obesity via the complement 3a receptor 1 (C3aR1) and enhancement of adrenergic-induced lipolysis. Conversely, the longer TLQP-62 peptide was suggested to induce insulin release in the INS b cell line. The aim of my study was to address possible roles of such peptides as peripherally released factors. Hence, the effects of their subcutaneous, or i.p. administration were studied on food intake, energy expenditure, body weight and glucose tolerance. The “spontaneous obesity” model in Siberian hamster was used (Long day adapted, Obese, vs. Short day adapted, Lean, or: LD vs. SD, respectively). In Lean (SD) animals, TLQP-21 (1mg/kg*day, 7 days) reduced cumulative meal duration and food intake (in the dark phase, p<0.03), while energy expenditure was significantly increased (p<0.04). As a result, body weight of treated animals was significantly reduced (p<0.04). Much lower, non significant changes were seen in Obese (LD) animals. On the other hand, either prolonged or acute treatment with TLQP-62 (1mg/kg*day, 7 days) enhanced glucose tolerance (upon glucose load, 5g/kg, i.p., p < 0.04), in both LD and SD hamsters. The corresponding insulin response was similarly increased (p < 0.05), while no changes were seen in either energy expenditure, food intake or body weight. In conclusion, although the two peptides studied share the sequence corresponding to the whole TLQP-21, they appear to possess very distinctive actions on metabolic and endocrine functions and regulations. Such findings are in agreement with the reported crucial role of the C-terminal end of TLQP-21 in determining both its bioactivity, as well as its interaction with the C3aR1 receptor. On the whole, the two peptides studied could exert their neuro-endocrine signalling and regulatory role via the hormonal route.