TLQP-21, A VGF-Derived Peptide Endowed of Endocrine and Extraendocrine Properties: Focus on In Vitro Calcium Signaling

Bresciani, Elena; Possenti, Roberta; Coco, Silvia; Rizzi, Laura; Meanti, Ramona; Molteni, Laura; Locatelli, Vittorio; Torsello, Antonio

doi:10.3390/ijms21010130

Cited by 11 publications

(10 citation statements)

References 78 publications

(143 reference statements)

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“…TLQP-21 has been implicated in various physiological processes including but not limited to metabolic regulation [3,9,28,32,33], nociception [6,34], sexual behavior [35], anxiety/stress-related behavior [36,37] (In this review, we will only highlight the major physiological functions of TLQP-21. Readers are directed to systematic review papers for a comprehensive discussion on the biological role of this neuropeptide [1,[38][39][40]).…”

Section: Biological Role Of Tlqp-21: In Vivo Studiesmentioning

confidence: 99%

The molecular identity of the TLQP-21 peptide receptor

Sahu

Nguyen

Rodrı́guez

et al. 2021

Cell. Mol. Life Sci.

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The TLQP-21 neuropeptide has been implicated in functions as diverse as lipolysis, neurodegeneration and metabolism, thus suggesting an important role in several human diseases. Three binding targets have been proposed for TLQP-21: C3aR1, gC1qR and HSPA8. The aim of this review is to critically evaluate the molecular identity of the TLQP-21 receptor and the proposed multi-receptor mechanism of action. Several studies confirm a critical role for C3aR1 in TLQP-21 biological activity and a largely conserved mode of binding, receptor activation and signaling with C3a, its first-identified endogenous ligand. Conversely, data supporting a role of gC1qR and HSPA8 in TLQP-21 activity remain limited, with no signal transduction pathways being described. Overall, C3aR1 is the only receptor for which a necessary and sufficient role in TLQP-21 activity has been confirmed thus far. This conclusion calls into question the validity of a multi-receptor mechanism of action for TLQP-21 and should inform future studies.

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Section: Biological Role Of Tlqp-21: In Vivo Studiesmentioning

confidence: 99%

The molecular identity of the TLQP-21 peptide receptor

Sahu

Nguyen

Rodrı́guez

et al. 2021

Cell. Mol. Life Sci.

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“…TLQP-21 is a neuropeptide with important endocrine and enteroendocrine functions demonstrated by multiple groups (2,3). Several studies have reported the complement receptor C3aR as an endogenous receptor for TLQP-21 (3,7,8,13,16). However, few have explored the potential actions of TLQP-21 on immune cells, despite the wide expression of C3aR on cells (9).…”

Section: Discussionmentioning

confidence: 99%

“…VGF is cleaved by the prohormone convertases such as prohormone convertase (PC) 1/3 and PC2 to generate a variety of bioactive peptides of low molecular weights (2). Among them, TLQP-21 is a 21-residue peptide derived from the C-terminus (residues 556-576) of the VGF precursor protein (3). Using the expression of VGF mRNA as a proxy, past studies have suggested the expression of TLQP-21 in the central and peripheral nervous system and in several neuroendocrine glands including the pancreas, adrenal medullar and pituitary, however, further investigation using more specific molecular tools are needed to confirm these findings (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…Among them, TLQP-21 is a 21-residue peptide derived from the C-terminus (residues 556-576) of the VGF precursor protein (3). Using the expression of VGF mRNA as a proxy, past studies have suggested the expression of TLQP-21 in the central and peripheral nervous system and in several neuroendocrine glands including the pancreas, adrenal medullar and pituitary, however, further investigation using more specific molecular tools are needed to confirm these findings (2)(3)(4). TLQP-21 possesses pleiotropic roles in physiology and cell biology, including reducing obesity by decreasing food intake and/or increasing energy expenditure; potentiating adrenergic-induced lipolysis in adipocytes; modulating gastric contractility and acid secretion; reproduction; nociception; neuroprotection and modulation of microglia functions (2,3).…”

Section: Introductionmentioning

confidence: 99%

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TLQP-21 is a low potency partial C3aR activator on human primary macrophages

Lee

et al. 2023

Front. Immunol.

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TLQP-21 is a 21-amino acid neuropeptide derived from the VGF precursor protein. TLQP-21 is expressed in the nervous system and neuroendocrine glands, and demonstrates pleiotropic roles including regulating metabolism, nociception and microglial functions. Several possible receptors for TLQP-21 have been identified, with complement C3a receptor (C3aR) being the most commonly reported. However, few studies have characterised the activity of TLQP-21 in immune cells, which represent the major cell type expressing C3aR. In this study, we therefore aimed to define the activity of both human and mouse TLQP-21 on cell signalling in primary human and mouse macrophages. We first confirmed that TLQP-21 induced ERK signalling in CHO cells overexpressing human C3aR, and did not activate human C5aR1 or C5aR2. TLQP-21 mediated ERK signalling was also observed in primary human macrophages. However, the potency for human TLQP-21 was 135,000-fold lower relative to C3a, and only reached 45% at the highest dose tested (10 μM). Unlike in humans, mouse TLQP-21 potently triggered ERK signalling in murine macrophages, reaching near full activation, but at ~10-fold reduced potency compared to C3a. We further confirmed the C3aR dependency of the TLQP-21 activities. Our results reveal significant discrepancy in TLQP-21 C3aR activity between human and murine receptors, with mouse TLQP-21 being consistently more potent than the human counterpart in both systems. Considering the supraphysiological concentrations of hTLQP-21 needed to only partially activate macrophages, it is likely that the actions of TLQP-21, at least in these immune cells, may not be mediated by C3aR in humans.

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“…TLQP-21, adiposit fonksiyonlarının yeni bir modülatörü ve obezite ile ilişkili hastalıkları çözümlemek için potansiyel bir aday olarak ortaya çıkmaktadır. Moleküler mekanizma hâlâ büyük oranda karakterize edilmemiş durumdadır (5) .…”

Section: Introductionunclassified

Determination of TLQP-21 Neuropeptide Plasma Level in Morbid Obese

Gülşah¹,

Soyacak²,

Kankaya³

et al. 2021

IKSST

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INTRODUCTION: In this study, it was aimed to measure TLQP-21 neuropeptide plasma levels, which is thought to be effective in preventing or treating obesity in morbidly obese and normal weight healthy individuals, and to make a comparison between both groups. METHODS: Fifty-one morbidly obese patients with a body mass index (BMI) of 40 kg/m2 and above and 22 healthy individuals of normal weight with a BMI between 18.5-24.9 kg/m2 without any metabolic disease were included in the study. Enzyme- linked immunosorbent analysis (ELISA) test was performed on plasma samples taken from all individuals participating in the study. All data were evaluated statistically. RESULTS: Although it was observed that TLQP-21 peptide values in morbidly obese individuals increased compared to healthy individuals with normal weight, this increase was not statistically significant (p>0.05) (p=0.718). The amount of TLQP-21 peptide was also evaluated according to gender distributions in the whole study group, but any statistically significant difference was not determined. DISCUSSION AND CONCLUSION: Our study showed that there is no difference in plasma levels of TLQP-21 neuropeptide, which is thought to play a key role in the treatment of obesity, in mordidly obese and healthy individuals.

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TLQP-21, A VGF-Derived Peptide Endowed of Endocrine and Extraendocrine Properties: Focus on In Vitro Calcium Signaling

Cited by 11 publications

References 78 publications

The molecular identity of the TLQP-21 peptide receptor

The molecular identity of the TLQP-21 peptide receptor

TLQP-21 is a low potency partial C3aR activator on human primary macrophages

Determination of TLQP-21 Neuropeptide Plasma Level in Morbid Obese

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