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Publication
Adropin: A cardio-metabolic hormone in the periphery, a neurohormone in the
brain?
Authors Butler AA, Havel PJ
Submitted By Submitted Externally on 4/23/2025
Status Published
Journal Peptides
Year 2025
Date Published 5/1/2025
Volume : Pages 187 : 171391
PubMed Reference 40097041
Abstract Whole-body metabolic homeostasis is regulated by physiological responses across
organs and tissues to proteins and peptides (<50 amino acids) released into the
interstitial and circulatory spaces. These secreted factors integrate signals of
metabolic status at both the cellular and systemic level, regulate the intake
and distribution of ingested and stored energy substrates across tissues, and
minimize toxicity from excessive excursions in circulating concentrations of
energy substrates (for example, glucotoxicity and lipotoxicity). The proteins
and peptides that are known to be secreted into circulation that are involved in
regulating metabolic processes represent a fraction of the secretome predicted
by the Human Proteome Atlas. Many undiscovered leads for targeting new therapies
for metabolic diseases may therefore exist. In this review, we discuss the
biology of adropin, the peptide encoded by the Energy Homeostasis Associated
(ENHO) gene. First described as a feeding-responsive, liver-secreted peptide
("hepatokine") involved in metabolic homeostasis, >?2 decades of research
indicate adropin is a stress-responsive peptide acting across multiple tissues,
vascular, and organ systems. Adropin modulates the responses of liver and muscle
to insulin and glucagon in regulating glucose homeostasis. Adropin inhibits
hepatic glucose production and stimulates glycolysis but also inhibits tissue
fibrosis and maintains vascular health in aging and metabolic disease states.
Adropin is also highly expressed in the central nervous system where recent data
suggest neuroprotective actions. Collectively, these results suggest the
potential for targeting adropin in reducing risk of both metabolic (metabolic
syndrome/type-2 diabetes) and neurodegenerative diseases in the context of aging
and obesity.




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