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Publication
Low plasma adropin concentrations increase risks of weight gain and metabolic
dysregulation in response to a high-sugar diet in male nonhuman primates.
Authors Butler AA, Zhang J, Price CA, Stevens JR, Graham JL, Stanhope KL, King S, Krauss
RM, Bremer AA, Havel PJ
Submitted By Submitted Externally on 2/12/2020
Status Published
Journal The Journal of biological chemistry
Year 2019
Date Published 6/1/2019
Volume : Pages 294 : 9706 - 9719
PubMed Reference 30988006
Abstract Mouse studies linking adropin, a peptide hormone encoded by the energy
homeostasis-associated (ENHO) gene, to biological clocks and to glucose and
lipid metabolism suggest a potential therapeutic target for managing diseases of
metabolism. However, adropin's roles in human metabolism are unclear. In silico
expression profiling in a nonhuman primate diurnal transcriptome atlas
(GSE98965) revealed a dynamic and diurnal pattern of ENHO expression. ENHO
expression is abundant in brain, including ventromedial and lateral hypothalamic
nuclei regulating appetite and autonomic function. Lower ENHO expression is
present in liver, lung, kidney, ileum, and some endocrine glands. Hepatic ENHO
expression associates with genes involved in glucose and lipid metabolism.
Unsupervised hierarchical clustering identified 426 genes co-regulated with ENHO
in liver, ileum, kidney medulla, and lung. Gene Ontology analysis of this
cluster revealed enrichment for epigenetic silencing by histone H3K27
trimethylation and biological processes related to neural function. Dietary
intervention experiments with 59 adult male rhesus macaques indicated low plasma
adropin concentrations were positively correlated with fasting glucose, plasma
leptin, and apolipoprotein C3 (APOC3) concentrations. During consumption of a
high-sugar (fructose) diet, which induced 10% weight gain, animals with low
adropin had larger increases of plasma leptin and more severe hyperglycemia.
Declining adropin concentrations were correlated with increases of plasma APOC3
and triglycerides. In summary, peripheral ENHO expression associates with
pathways related to epigenetic and neural functions, and carbohydrate and lipid
metabolism, suggesting co-regulation in nonhuman primates. Low circulating
adropin predicts increased weight gain and metabolic dysregulation during
consumption of a high-sugar diet.




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