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PHOENIXIN-20 IN MICE: TISSUE DISTRIBUTION, IN VITRO ENDOCRINE ACTIONS AND IN VIVO EFFECTS ON FOOD INTAKE

Date

2021-01-19

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Thesis

Degree Level

Masters

Abstract

Energy homeostasis is regulated by the balance between food intake and energy expenditure, which is partly controlled by the cross-talk between central and peripheral hormonal signals. Phoenixin (PNX) is a recently discovered pleiotropic neuropeptide with isoforms of 14 (PNX-14) and 20 (PNX-20) amino acids being functionally active among most vertebrates. It is well known as a potent reproductive peptide in vertebrates regulating through hypothalamo-pituitary-gonadal axis (HPG). Apart from that, it has been identified to be involved in food intake during the light phase when injected intracerebroventricularly (ICV) in rats. In addition to this, plasma levels of PNX also increased after food intake in rats, showing that it might have possible roles in energy homeostasis due to its involvement in energy utilizing processes including food intake and reproduction. I hypothesized that the gut is a source and site of action of PNX and PNX has metabolic effects in mice. In this study, I focused on determining whether peripheral administration of PNX-20 regulates energy balance in male C57/BL6J mice. I found the presence of PNX and its putative receptor, super-conserved receptor expressed in brain (SREB3) in the gut of male C57/BL6J mice and MGN3-1 (mouse stomach endocrine) and STC-1 (mouse intestinal enteroendocrine) cell lines using immunohisto/cytochemistry and imaging. In MGN3-1, PNX-20 significantly upregulated ghrelin (10 nM) and GOAT mRNA (1000 nM) at 6 h whereas in STC-1, it significantly suppressed CCK (100 nM) at 2 h. Intraperitoneal (IP) administration (50 μg/kg body weight PNX-20) upregulated light phase food intake at 6 h, but had no other metabolic effects. Similarly, in continuous subcutaneous infusion for 7 days, I did not find any metabolic effect of PNX-20. While my results indicate that PNX-20 is a selective regulator of gut metabolic hormones, it did not support my hypothesis that PNX-20 is a metabolic peptide in mice.

Description

Keywords

PNX, IP, CLAMS, Osmotic pumps

Citation

Degree

Master of Science (M.Sc.)

Department

Veterinary Biomedical Sciences

Program

Veterinary Biomedical Sciences

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