PUBLICATION

Phoenixin-20 (PNX-20) Suppresses Food Intake, Modulates Glucoregulatory Enzymes, and Enhances Glycolysis in Zebrafish

Authors
Rajeswari, J.J., Blanco, A.M., Unniappan, S.
ID
ZDB-PUB-200403-174
Date
2020
Source
American journal of physiology. Regulatory, integrative and comparative physiology   318(5): R917-R928 (Journal)
Registered Authors
Unniappan, Suraj
Keywords
Food Intake, Glucose homeostasis, Metabolism, Phoenixin, Zebrafish
MeSH Terms
  • Animals
  • Appetite Depressants/pharmacology*
  • Appetite Regulation/drug effects
  • Cell Line
  • Eating/drug effects*
  • Feeding Behavior/drug effects*
  • Female
  • Gene Expression Regulation
  • Glucose/metabolism*
  • Glycolysis/drug effects*
  • Glycolysis/genetics
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Homeodomain Proteins/pharmacology*
  • Male
  • Peptide Fragments/genetics
  • Peptide Fragments/metabolism
  • Peptide Fragments/pharmacology*
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/pharmacology*
PubMed
32208925 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.
Abstract
Phoenixin is a 20 amino acid peptide (PNX-20) cleaved from the small integral membrane protein 20 (SMIM20), with multiple biological roles in mammals. However, its role in non-mammalian vertebrates is poorly understood. This research aimed to determine whether PNX-20 influences feeding and metabolism in zebrafish. The mRNAs encoding SMIM20 and its putative receptor, super conserved receptor expressed in brain 3 (SREB3), are present in both central and peripheral tissues of zebrafish. Immunohistochemical analysis confirmed the presence of PNX-like immunoreactivity in the gut and zebrafish liver (ZFL) cell line. We also found that short-term fasting (7 days) significantly decreased smim20 mRNA expression in the brain, gut, liver, gonad, and muscle, which suggests a role for PNX-20 in food intake regulation. Indeed, single intraperitoneal injection of 1000 ng/g body weight PNX-20 reduced feeding in both male and female zebrafish, likely in part by enhancing hypothalamic cart and reducing hypothalamic/gut preproghrelin mRNAs. Furthermore, present results demonstrated that PNX-20 modulates the expression of genes involved in glucose transport and metabolism in ZFL cells. In general terms, such PNX-induced modulation of gene expression was characterized by the upregulation of glycolytic genes and the downregulation of gluconeogenic genes. A kinetic study of the ATP production rate from both glycolytic and mitochondrial pathways demonstrated that PNX-20-treated ZFL cells exhibited significantly higher ATP production rate associated to glycolysis than control cells, confirming a positive role for PNX-20 on glycolysis. Together, these results point out that PNX-20 is an anorexigen with important metabolic roles in zebrafish.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping