Role of the Novel Peptide Phoenixin in Stress Response and Possible Interactions with Nesfatin-1

Abstract

The novel peptide phoenixin was shown to be involved in several physiological processes ranging from reproduction to food intake. Interest in this protein has steadily increased over the last few years and its known implications have become much broader, playing a role in glucose homeostasis, anxiety, nociception, and pruritus. Phoenixin is expressed in a multitude of organs such as the small intestine, pancreas, and in the hypothalamus, as well as several other brain nuclei influencing numerous physiological functions. Its highly conserved amino-acid sequence amongst species leads to the assumption, that phoenixin might be involved in essential physiological functions. Its co-expression and opposing functionality to the extensively studied peptide nesfatin-1 has given rise to the idea of a possible counterbalancing role. Several recent publications focused on phoenixin’s role in stress reactions, namely restraint stress and lipopolysaccharide-induced inflammation response, in which also nesfatin-1 is known to be altered. This review provides an overview on the phoenixins and nesfatin-1 properties and putative effects, and especially highlights the recent developments on their role and interaction in the response to response.

Regulation and physiological functions of phoenixin

“…administration of phoenixin, the number of nesfatin-1 immunoreactive neurons was increased in the lateral septal nucleus, PVN, NTS, and SON ( Friedrich et al, 2019 ). Recently, Friedrich et al proposed that phoenixin had possible physiological interactions with nesfatin-1, especially in stress response ( Friedrich and Stengel, 2021 ). Under restraint stress, the nesfatin-1 level in rat serum was increased, whereas the phoenixin level was decreased ( Schalla, et al, 2020 ).…”

Premetazoan Origin of Neuropeptide Signaling

“…Pharmacological experiments with the mature PNX peptides suggest that PNX-14 and PNX-20 act as pleiotropic neuropeptides in mammals. PNX peptides modulate heart function, memory, anxiety, food intake, and reproduction ( Clarke and Dhillo 2019 ; Schalla and Stengel 2019 ; Billert et al 2020 ; Haddock et al 2020 ; Ma et al 2020 ; Schalla et al 2020 ; Friedrich and Stengel 2021 ; Yao et al 2021 ). Strikingly for a proneuropeptide, the SMIM20 (also called MITRAC7) precursor also localizes to mitochondria in U2OS and HEK293 cells and functions as a mitochondrial chaperone during cytochrome-c oxidase complex assembly ( Dennerlein et al 2015 ).…”

“…So far, only nesfatin-1 was shown to have a physiological function ( Oh-I et al 2006 ; Schalla and Stengel 2018 ). Different functions of nesfatin-1 have been reported in vertebrates, including the regulation of glucose metabolism, reproduction, anxiety, and responses to stress ( Schalla and Stengel 2018 ; Friedrich and Stengel 2021 ). Its role as a satiety-inducing factor has been widely reported in mammals and fish ( Ayada et al 2015 ; Sundarrajan et al 2016 ; Rupp et al 2021 ).…”

Pre-metazoan origin of neuropeptide signalling

“…Recently, neuropeptidomic searches in arthropod transcriptomes revealed phoenixin precursors with conserved cleavage sites to produce the mature PNX peptide PNX14 and PNX-20 (Nguyen et al 2018). PNX is involved in many different physiological functions in mammals, such as cardio-modulation, memory, anxiety, food intake and reproduction (Clarke and Dhillo 2019;Schalla and Stengel 2019;Billert et al 2020;Haddock et al 2020;Ma et al 2020;Schalla et al 2020;Friedrich and Stengel 2021;Yao et al 2021). The mechanism of signalling of PNX, an orphan ligand, remains unclear.…”

“…So far, only nesfatin-1 was shown to have a physiological function (Oh-I et al 2006;Schalla and Stengel 2018). Different functions of nesfatin-1 have been reported in vertebrates, such as glucose metabolism and the regulation of reproduction, stress and anxiety responses (Schalla and Stengel 2018;Friedrich and Stengel 2021). Its role as a satiety-inducing factor has been widely reported in mammals and fish (Ayada et al 2015;Sundarrajan et al 2016;Rupp et al 2021).…”