VFG-Derived Peptide TLQP-21

VFG-Derived Peptide TLQP-21 Biology and Pathophysiology

The Vgf gene is a member of the extended granin family of peptides [1]. VGF encodes a 615 amino acid protein (617 in rodents) that is stored in dense core granules and processed to yield several bioactive peptides, released through the regulated pathway. At least 7 peptides have been shown to possess non redundant biological functions in rodents while VGF fragments are increasingly recognized as useful biomarkers for human disease [1]. We have recently identified and functionally characterized the C-terminal internal fragment designated TLQP-21 [2]. TLQP-21 is a multifunctional peptide active in the regulation of energy balance, glucose homeostasis, gastric function, nociception, reproduction and stress [1]. Intracerebroventricular infusion of TLQP-21 increases energy expenditure and prevents obesity without activating central hypothalamic neuropeptides or feeding [2]. In periphery, TLQP-21 [3] is co-stored with norepinephrine-synthesizing enzyme tyrosine hydroxylase in sympathetic nerves innervating the adipose organ; increases lipolysis downstream of β-adrenergic receptor signaling pathway; increases sympathetic innervation to adipose fat pads and decreases adipocytes diameters without exerting negative cardiovascular effects or activating energy expenditure [3].

We are currently investigating the molecular mechanism of TLQP-21 induced pro-lipolysis effects. We are also performing a structure-function relationship study by using mutagenesis, functional bio-assays and solution and solid-state NMR spectroscopy.

The long term goal is to use molecular and physiological knowledge to develop innovative drugs for the treatment of obesity and type 2 diabetes.

References: 1.Bartolomucci et al., Endocr Rev. 2011;32:755-97; 2.Bartolomucci et al., Proc Natl Acad Sci USA. 2006;103:14584-9; 3.Possenti et al., Biochem J. 2012;441:511-22.