FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2939733089> ?p ?o ?g. }

• W2939733089 endingPage "9719" @default.
• W2939733089 startingPage "9706" @default.
• W2939733089 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. 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. Setting fire to fatJournal of Biological ChemistryVol. 294Issue 25PreviewAdropin is a liver-secreted peptide that is crucial for metabolic health. However, the molecular functions and clinical significance of adropin have not been adequately explored. Butler et al. now investigate adropin expression profiles and links to cardiometabolic disease risk in two nonhuman primate models, increasing our translational and mechanistic understanding of this fascinating hormone. Full-Text PDF Open Access The energy homeostasis–associated (ENHO) gene contains a single highly-conserved ORF (adropin1–76). In silico analysis indicates a secreted domain (adropin34–76) released from a secretory signal (adropin1–33) by proteolysis (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.Cell Metab. 2008; 8 (19041763): 468-48110.1016/j.cmet.2008.10.011Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 2Uhlén M. Fagerberg L. Hallström B.M. Lindskog C. Oksvold P. Mardinoglu A. Sivertsson Å. Kampf C. Sjöstedt E. Asplund A. Olsson I. Edlund K. Lundberg E. Navani S. Szigyarto C.A. et al.Proteomics. Tissue-based map of the human proteome.Science. 2015; 347 (25613900): 126041910.1126/science.1260419Crossref PubMed Scopus (7354) Google Scholar). Adropin34–76 has bioactivity that influences carbohydrate and lipid metabolism when administered to rodents and cultured cells (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.Cell Metab. 2008; 8 (19041763): 468-48110.1016/j.cmet.2008.10.011Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 3Thapa D. Stoner M.W. Zhang M. Xie B. Manning J.R. Guimaraes D. Shiva S. Jurczak M.J. Scott I. Adropin regulates pyruvate dehydrogenase in cardiac cells via a novel GPCR–MAPK–PDK4 signaling pathway.Redox Biol. 2018; 18 (29909017): 25-3210.1016/j.redox.2018.06.003Crossref PubMed Scopus (48) Google Scholar4Sato K. Yamashita T. Shirai R. Shibata K. Okano T. Yamaguchi M. Mori Y. Hirano T. Watanabe T. Adropin contributes to anti-atherosclerosis by suppressing monocyte-endothelial cell adhesion and smooth muscle cell proliferation.Int. J. Mol. Sci. 2018; 19 (29701665): E129310.3390/ijms19051293Crossref PubMed Scopus (48) Google Scholar, 5Yang C. DeMars K.M. Hawkins K.E. Candelario-Jalil E. Adropin reduces paracellular permeability of rat brain endothelial cells exposed to ischemia-like conditions.Peptides. 2016; 81 (27020249): 29-3710.1016/j.peptides.2016.03.009Crossref PubMed Scopus (27) Google Scholar, 6Akcilar R. Kocak F.E. Simsek H. Akcilar A. Bayat Z. Ece E. Kokdasgil H. Antidiabetic and hypolipidemic effects of adropinin streptozotocin-induced type 2 diabetic rats.Bratisl. Lek. Listy. 2016; 117 (26830041): 100-105PubMed Google Scholar, 7Akcıilar R. Emel Koçak F. Şimşek H. Akcıilar A. Bayat Z. Ece E. Kökdaşgil H. The effect of adropin on lipid and glucose metabolism in rats with hyperlipidemia.Iran J. Basic Med. Sci. 2016; 19 (27114793): 245-251PubMed Google Scholar, 8Ghoshal S. Stevens J.R. Billon C. Girardet C. Sitaula S. Leon A.S. Rao D.C. Skinner J.S. Rankinen T. Bouchard C. Nuñez M.V. Stanhope K.L. Howatt D.A. Daugherty A. Zhang J. et al.Adropin: an endocrine link between the biological clock and cholesterol homeostasis.Mol. Metab. 2018; 8 (29331507): 51-6410.1016/j.molmet.2017.12.002Crossref PubMed Scopus (48) Google Scholar, 9Gao S. McMillan R.P. Zhu Q. Lopaschuk G.D. Hulver M.W. Butler A.A. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance.Mol. Metab. 2015; 4 (25830094): 310-32410.1016/j.molmet.2015.01.005Crossref PubMed Scopus (115) Google Scholar, 10Gao S. McMillan R.P. Jacas J. Zhu Q. Li X. Kumar G.K. Casals N. Hegardt F.G. Robbins P.D. Lopaschuk G.D. Hulver M.W. Butler A.A. Regulation of substrate oxidation preferences in muscle by the peptide hormone adropin.Diabetes. 2014; 63 (24848071): 3242-325210.2337/db14-0388Crossref PubMed Scopus (72) Google Scholar, 11Ganesh Kumar K. Zhang J. Gao S. Rossi J. McGuinness O.P. Halem H.H. Culler M.D. Mynatt R.L. Butler A.A. Adropin deficiency is associated with increased adiposity and insulin resistance.Obesity. 2012; 20 (22318315): 1394-140210.1038/oby.2012.31Crossref PubMed Scopus (183) Google Scholar12Thapa D. Xie B. Zhang M. Stoner M.W. Manning J.R. Huckestein B.R. Edmunds L.R. Mullett S.J. McTiernan C.F. Wendell S.G. Jurczak M.J. Scott I. Adropin treatment restores cardiac glucose oxidation in pre-diabetic obese mice.J. Mol. Cell. Cardiol. 2019; 129 (30822408): 174-17810.1016/j.yjmcc.2019.02.012Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Adropin immunoreactivity has been measured in the circulation of humans, nonhuman primates, and mice (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.Cell Metab. 2008; 8 (19041763): 468-48110.1016/j.cmet.2008.10.011Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 8Ghoshal S. Stevens J.R. Billon C. Girardet C. Sitaula S. Leon A.S. Rao D.C. Skinner J.S. Rankinen T. Bouchard C. Nuñez M.V. Stanhope K.L. Howatt D.A. Daugherty A. Zhang J. et al.Adropin: an endocrine link between the biological clock and cholesterol homeostasis.Mol. Metab. 2018; 8 (29331507): 51-6410.1016/j.molmet.2017.12.002Crossref PubMed Scopus (48) Google Scholar, 11Ganesh Kumar K. Zhang J. Gao S. Rossi J. McGuinness O.P. Halem H.H. Culler M.D. Mynatt R.L. Butler A.A. Adropin deficiency is associated with increased adiposity and insulin resistance.Obesity. 2012; 20 (22318315): 1394-140210.1038/oby.2012.31Crossref PubMed Scopus (183) Google Scholar, 13Bremer A.A. Stanhope K.L. Graham J.L. Cummings B.P. Ampah S.B. Saville B.R. Havel P.J. Fish oil supplementation ameliorates fructose-induced hypertriglyceridemia and insulin resistance in adult male rhesus macaques.J. Nutr. 2014; 144 (24108131): 5-1110.3945/jn.113.178061Crossref PubMed Scopus (51) Google Scholar). However, retention of adropin1–76 in plasma membrane fractions has been observed (14Wong C.M. Wang Y. Lee J.T. Huang Z. Wu D. Xu A. Lam K.S. Adropin is a brain membrane-bound protein regulating physical activity via the NB-3/Notch signaling pathway in mice.J. Biol. Chem. 2014; 289 (25074942): 25976-2598610.1074/jbc.M114.576058Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar). The secretory processes and protein structure of adropin thus remain under investigation. Experiments performed in male C57BL/6J (B6) mice implicate a role for adropin in metabolic homeostasis. Treating diet-induced obese (DIO) 4The abbreviations used are: DIOdiet-induced obeseANOVAanalysis of varianceRORretinoic acid–related orphan receptorLDLlow density lipoproteinHDLhigh density lipoproteinIDLintermediate-density lipoproteinVLDLvery-low density lipoproteinVMHventromedial hypothalamusFPKMfragments per kb of transcript per millionTGtriglycerideAdrTGadropin transgenicIMion mobilityCCKcholecystokininGSEAGene Set Enrichment AnalysisCpGcytosine-phosphate-guanine-C-cholesterol. B6 mice with exogenous adropin34–76 reduce adiposity (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.Cell Metab. 2008; 8 (19041763): 468-48110.1016/j.cmet.2008.10.011Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). Conversely, adropin deficiency increases adiposity without altering food intake (11Ganesh Kumar K. Zhang J. Gao S. Rossi J. McGuinness O.P. Halem H.H. Culler M.D. Mynatt R.L. Butler A.A. Adropin deficiency is associated with increased adiposity and insulin resistance.Obesity. 2012; 20 (22318315): 1394-140210.1038/oby.2012.31Crossref PubMed Scopus (183) Google Scholar). In mice and cultured cells, adropin34–76 increases activity of the pyruvate dehydrogenase complex, enhancing the coupling of glycolysis with the tricarboxylic acid cycle and oxidative glucose metabolism (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.Cell Metab. 2008; 8 (19041763): 468-48110.1016/j.cmet.2008.10.011Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 3Thapa D. Stoner M.W. Zhang M. Xie B. Manning J.R. Guimaraes D. Shiva S. Jurczak M.J. Scott I. Adropin regulates pyruvate dehydrogenase in cardiac cells via a novel GPCR–MAPK–PDK4 signaling pathway.Redox Biol. 2018; 18 (29909017): 25-3210.1016/j.redox.2018.06.003Crossref PubMed Scopus (48) Google Scholar, 9Gao S. McMillan R.P. Zhu Q. Lopaschuk G.D. Hulver M.W. Butler A.A. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance.Mol. Metab. 2015; 4 (25830094): 310-32410.1016/j.molmet.2015.01.005Crossref PubMed Scopus (115) Google Scholar, 10Gao S. McMillan R.P. Jacas J. Zhu Q. Li X. Kumar G.K. Casals N. Hegardt F.G. Robbins P.D. Lopaschuk G.D. Hulver M.W. Butler A.A. Regulation of substrate oxidation preferences in muscle by the peptide hormone adropin.Diabetes. 2014; 63 (24848071): 3242-325210.2337/db14-0388Crossref PubMed Scopus (72) Google Scholar, 12Thapa D. Xie B. Zhang M. Stoner M.W. Manning J.R. Huckestein B.R. Edmunds L.R. Mullett S.J. McTiernan C.F. Wendell S.G. Jurczak M.J. Scott I. Adropin treatment restores cardiac glucose oxidation in pre-diabetic obese mice.J. Mol. Cell. Cardiol. 2019; 129 (30822408): 174-17810.1016/j.yjmcc.2019.02.012Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Treatment with adropin34–76 also enhances insulin signaling, glucose tolerance, and whole-body oxidative glucose disposal in DIO B6 mice independently of weight loss (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.Cell Metab. 2008; 8 (19041763): 468-48110.1016/j.cmet.2008.10.011Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 9Gao S. McMillan R.P. Zhu Q. Lopaschuk G.D. Hulver M.W. Butler A.A. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance.Mol. Metab. 2015; 4 (25830094): 310-32410.1016/j.molmet.2015.01.005Crossref PubMed Scopus (115) Google Scholar). Male B6 mice lacking either one or both functional copies of the Enho gene exhibit insulin resistance and impaired glucose tolerance (11Ganesh Kumar K. Zhang J. Gao S. Rossi J. McGuinness O.P. Halem H.H. Culler M.D. Mynatt R.L. Butler A.A. Adropin deficiency is associated with increased adiposity and insulin resistance.Obesity. 2012; 20 (22318315): 1394-140210.1038/oby.2012.31Crossref PubMed Scopus (183) Google Scholar, 15Chen S. Zeng K. Liu Q.C. Guo Z. Zhang S. Chen X.R. Lin J.H. Wen J.P. Zhao C.F. Lin X.H. Gao F. Adropin deficiency worsens HFD-induced metabolic defects.Cell Death Dis. 2017; 8 (28837146): e300810.1038/cddis.2017.362Crossref PubMed Google Scholar). Partial loss of adropin signaling is thus sufficient to result in impaired glucose homeostasis. diet-induced obese analysis of variance retinoic acid–related orphan receptor low density lipoprotein high density lipoprotein intermediate-density lipoprotein very-low density lipoprotein ventromedial hypothalamus fragments per kb of transcript per million triglyceride adropin transgenic ion mobility cholecystokinin Gene Set Enrichment Analysis cytosine-phosphate-guanine -cholesterol. The initial studies examining regulation of hepatic adropin expression in mice indicated rapid effects of fasting and intake of dietary macronutrients (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.Cell Metab. 2008; 8 (19041763): 468-48110.1016/j.cmet.2008.10.011Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 16Kuhla A. Hahn S. Butschkau A. Lange S. Wree A. Vollmar B. Lifelong caloric restriction reprograms hepatic fat metabolism in mice.J. Gerontol. A Biol. Sci. Med. Sci. 2014; 69 (24149425): 915-92210.1093/gerona/glt160Crossref PubMed Scopus (52) Google Scholar17Partridge C.G. Fawcett G.L. Wang B. Semenkovich C.F. Cheverud J.M. The effect of dietary fat intake on hepatic gene expression in LG/J AND SM/J mice.BMC Genomics. 2014; 15 (24499025): 9910.1186/1471-2164-15-99Crossref PubMed Scopus (25) Google Scholar, 18Bushkofsky J.R. Maguire M. Larsen M.C. Fong Y.H. Jefcoate C.R. Cyp1b1 affects external control of mouse hepatocytes, fatty acid homeostasis and signaling involving HNF4α and PPARα.Arch. Biochem. Biophys. 2016; 597 (27036855): 30-4710.1016/j.abb.2016.03.030Crossref PubMed Scopus (11) Google Scholar19Larsen M.C. Bushkofsky J.R. Gorman T. Adhami V. Mukhtar H. Wang S. Reeder S.B. Sheibani N. Jefcoate C.R. Cytochrome P450 1B1: an unexpected modulator of liver fatty acid homeostasis.Arch. Biochem. Biophys. 2015; 571 (25703193): 21-3910.1016/j.abb.2015.02.010Crossref PubMed Scopus (35) Google Scholar). More recent studies indicate rhythmicity of hepatic adropin expression under the control of core elements of the biological clock (8Ghoshal S. Stevens J.R. Billon C. Girardet C. Sitaula S. Leon A.S. Rao D.C. Skinner J.S. Rankinen T. Bouchard C. Nuñez M.V. Stanhope K.L. Howatt D.A. Daugherty A. Zhang J. et al.Adropin: an endocrine link between the biological clock and cholesterol homeostasis.Mol. Metab. 2018; 8 (29331507): 51-6410.1016/j.molmet.2017.12.002Crossref PubMed Scopus (48) Google Scholar). Diurnal cycles of transcriptional activation or repression by retinoic acid–related orphan receptors (ROR) or REV-ERB contribute to the rhythmicity of the biological clock (20Kojetin D.J. Burris T.P. REV-ERB and ROR nuclear receptors as drug targets.Nat. Rev. Drug Discov. 2014; 13 (24577401): 197-21610.1038/nrd4100Crossref PubMed Scopus (352) Google Scholar, 21Lazar M.A. Sassone-Corsi P. Christen Y. A Time for Metabolism and Hormones. Springer, New York2016: 63-70Crossref Scopus (6) Google Scholar22Bass J. Sassone-Corsi P. Christen Y. A Time for Metabolism and Hormones. Springer, New York2016: 25-32Crossref Scopus (6) Google Scholar) and to hepatic Enho expression (8Ghoshal S. Stevens J.R. Billon C. Girardet C. Sitaula S. Leon A.S. Rao D.C. Skinner J.S. Rankinen T. Bouchard C. Nuñez M.V. Stanhope K.L. Howatt D.A. Daugherty A. Zhang J. et al.Adropin: an endocrine link between the biological clock and cholesterol homeostasis.Mol. Metab. 2018; 8 (29331507): 51-6410.1016/j.molmet.2017.12.002Crossref PubMed Scopus (48) Google Scholar). Members of the ROR (α, β, and γ) and REV-ERB (α and β) families bind competitively to common genomic elements, regulating transcription of genes involved in carbohydrate and lipid metabolism; these nuclear receptors also possess ligand-binding domains responsive to cellular lipid and redox conditions (20Kojetin D.J. Burris T.P. REV-ERB and ROR nuclear receptors as drug targets.Nat. Rev. Drug Discov. 2014; 13 (24577401): 197-21610.1038/nrd4100Crossref PubMed Scopus (352) Google Scholar). Involvement of ROR and REV-ERB in regulating ENHO transcription provides a plausible mechanism linking adropin expression to biological clocks. As adropin regulates glucose and fat oxidation (3Thapa D. Stoner M.W. Zhang M. Xie B. Manning J.R. Guimaraes D. Shiva S. Jurczak M.J. Scott I. Adropin regulates pyruvate dehydrogenase in cardiac cells via a novel GPCR–MAPK–PDK4 signaling pathway.Redox Biol. 2018; 18 (29909017): 25-3210.1016/j.redox.2018.06.003Crossref PubMed Scopus (48) Google Scholar, 9Gao S. McMillan R.P. Zhu Q. Lopaschuk G.D. Hulver M.W. Butler A.A. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance.Mol. Metab. 2015; 4 (25830094): 310-32410.1016/j.molmet.2015.01.005Crossref PubMed Scopus (115) Google Scholar, 10Gao S. McMillan R.P. Jacas J. Zhu Q. Li X. Kumar G.K. Casals N. Hegardt F.G. Robbins P.D. Lopaschuk G.D. Hulver M.W. Butler A.A. Regulation of substrate oxidation preferences in muscle by the peptide hormone adropin.Diabetes. 2014; 63 (24848071): 3242-325210.2337/db14-0388Crossref PubMed Scopus (72) Google Scholar, 12Thapa D. Xie B. Zhang M. Stoner M.W. Manning J.R. Huckestein B.R. Edmunds L.R. Mullett S.J. McTiernan C.F. Wendell S.G. Jurczak M.J. Scott I. Adropin treatment restores cardiac glucose oxidation in pre-diabetic obese mice.J. Mol. Cell. Cardiol. 2019; 129 (30822408): 174-17810.1016/j.yjmcc.2019.02.012Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar), it may have a role in translating cues from biological clock genes into rhythms in carbohydrate and lipid metabolism. The relationships between adropin and metabolism in humans are less clear and remain under investigation. Several studies have reported that fasting plasma adropin concentrations are lower in humans with insulin resistance (23Zang H. Jiang F. Cheng X. Xu H. Hu X. Serum adropin levels are decreased in Chinese type 2 diabetic patients and negatively correlated with body mass index.Endocr J. 2018; 65 (29669965): 685-69110.1507/endocrj.EJ18-0060Crossref PubMed Scopus (36) Google Scholar24Beigi A. Shirzad N. Nikpour F. Nasli Esfahani E. Emamgholipour S. Bandarian F. Association between serum adropin levels and gestational diabetes mellitus; a case-control study.Gynecol. Endocrinol. 2015; 31 (26376846): 939-94110.3109/09513590.2015.1081681Crossref PubMed Scopus (31) Google Scholar, 25Celik E. Yilmaz E. Celik O. Ulas M. Turkcuoglu I. Karaer A. Simsek Y. Minareci Y. Aydin S. Maternal and fetal adropin levels in gestational diabetes mellitus.J. Perinat. Med. 2013; 41 (23314506): 375-38010.1515/jpm-2012-0227Crossref PubMed Scopus (59) Google Scholar26Stevens J.R. Kearney M.L. St-Onge M.P. Stanhope K.L. Havel P.J. Kanaley J.A. Thyfault J.P. Weiss E.P. Butler A.A. Inverse association between carbohydrate consumption and plasma adropin concentrations in humans.Obesity. 2016; 24 (27460714): 1731-174010.1002/oby.21557Crossref PubMed Scopus (27) Google Scholar). Relationships have been observed between circulating adropin concentrations and fasting glucose levels in children with Prader-Willi syndrome, as well as circulating levels of the gut peptide obestatin in children (27Orsso C.E. Butler A.A. Muehlbauer M.J. Cui H.N. Rubin D.A. Pakseresht M. Butler M.G. Prado C.M. Freemark M. Haqq A.M. Obestatin and adropin in Prader-Willi syndrome and nonsyndromic obesity: associations with weight, BMI-z, and HOMA-IR.Pediatr. Obes. 2019; 14 (30589518): e1249310.1111/ijpo.12493Crossref PubMed Scopus (9) Google Scholar). A more recent study using diverse age groups observed an inverse association between plasma adropin concentrations and indices of atherogenic hypercholesterolemia (total cholesterol, LDL-C, and nonHDL-C) in males possibly mediated by suppression of ENHO expression by cholesterol (8Ghoshal S. Stevens J.R. Billon C. Girardet C. Sitaula S. Leon A.S. Rao D.C. Skinner J.S. Rankinen T. Bouchard C. Nuñez M.V. Stanhope K.L. Howatt D.A. Daugherty A. Zhang J. et al.Adropin: an endocrine link between the biological clock and cholesterol homeostasis.Mol. Metab. 2018; 8 (29331507): 51-6410.1016/j.molmet.2017.12.002Crossref PubMed Scopus (48) Google Scholar). In adults, plasma adropin concentrations are positively correlated with dietary fat intake and inversely with carbohydrate intake (26Stevens J.R. Kearney M.L. St-Onge M.P. Stanhope K.L. Havel P.J. Kanaley J.A. Thyfault J.P. Weiss E.P. Butler A.A. Inverse association between carbohydrate consumption and plasma adropin concentrations in humans.Obesity. 2016; 24 (27460714): 1731-174010.1002/oby.21557Crossref PubMed Scopus (27) Google Scholar, 28St-Onge M.P. Shechter A. Shlisky J. Tam C.S. Gao S. Ravussin E. Butler A.A. Fasting plasma adropin concentrations correlate with fat consumption in human females.Obesity. 2014; 22 (24115373): 1056-106310.1002/oby.20631Crossref PubMed Scopus (32) Google Scholar) and increase during fructose consumption (29Butler A.A. St-Onge M.P. Siebert E.A. Medici V. Stanhope K.L. Havel P.J. Differential responses of plasma adropin concentrations to dietary glucose or fructose consumption in humans.Sci. Rep. 2015; 5 (26435060): 1469110.1038/srep14691Crossref PubMed Scopus (26) Google Scholar). Differences in dietary preferences (fat versus carbohydrates) could be a confounding variable in cross-sectional human studies examining the relationship between circulating adropin levels and indices of cardio-metabolic risk. Here, we report the results from two studies investigating adropin physiology in nonhuman primates. Nonhuman primates are useful models for translating preclinical data obtained using rodents to clinical studies in humans (30Kleinert M. Clemmensen C. Hofmann S.M. Moore M.C. Renner S. Woods S.C. Huypens P. Beckers J. de Angelis M.H. Schürmann A. Bakhti M. Klingenspor M. Heiman M. Cherrington A.D. Ristow M. et al.Animal models of obesity and diabetes mellitus.Nat. Rev. Endocrinol. 2018; 14 (29348476): 140-16210.1038/nrendo.2017.161Crossref PubMed Scopus (415) Google Scholar, 31Havel P.J. Kievit P. Comuzzie A.G. Bremer A.A. Use and importance of nonhuman primates in metabolic disease research: current state of the field.ILAR J. 2017; 58 (29216341): 251-26810.1093/ilar/ilx031Crossref PubMed Scopus (35) Google Scholar32Cox L.A. Olivier M. Spradling-Reeves K. Karere G.M. Comuzzie A.G. VandeBerg J.L. Nonhuman primates and translational research-cardiovascular disease.ILAR J. 2017; 58 (28985395): 235-25010.1093/ilar/ilx025Crossref PubMed Scopus (36) Google Scholar). Other advantages to using nonhuman primate models include minimizing variability from diet and personal history and access to a number of tissues that cannot normally be obtained in humans. Baboons (Papio anubis) and rhesus macaques (Macaca mulatta) belong to a closely related tribe (Papionini) that diverged from lineages leading to the evolution of humans and great apes 25–28 million years ago (33Rogers J. Gibbs R.A. Comparative primate genomics: emerging patterns of genome content and dynamics.Nat. Rev. Genet. 2014; 15 (24709753): 347-35910.1038/nrg3707Crossref PubMed Scopus (158) Google Scholar). We used the transcriptome atlas of a nonhuman primate (baboon) (34Mure L.S. Le H.D. Benegiamo G. Chang M.W. Rios L. Jillani N. Ngotho M. Kariuki T. Dkhissi-Benyahya O. Cooper H.M. Panda S. Diurnal transcriptome atlas of a primate across major neural and peripheral tissues.Science. 2018; 359 (29439024): eaao031810.1126/science.aao0318Crossref PubMed Scopus (351) Google Scholar) to profile diurnal ENHO expression. We then investigated the relationships between plasma adropin concentrations and indices and risk factors for metabolic dysregulation in a well-characterized rhesus macaque model of a high-sugar (fructose) diet–induced obesity, insulin resistance, and dyslipidemia (13Bremer A.A. Stanhope K.L. Graham J.L. Cummings B.P. Ampah S.B. Saville B.R. Havel P.J. Fish oil supplementation ameliorates fructose-induced hypertriglyceridemia and insulin resistance in adult male rhesus macaques.J. Nutr. 2014; 144 (24108131): 5-1110.3945/jn.113.178061Crossref PubMed Scopus (51) Google Scholar, 31Havel P.J. Kievit P. Comuzzie A.G. Bremer A.A. Use and importance of nonhuman primates in metabolic disease research: current state of the field.ILAR J. 2017; 58 (29216341): 251-26810.1093/ilar/ilx031Crossref PubMed Scopus (35) Google Scholar, 35Bremer A.A. Stanhope K.L. Graham J.L. Cummings B.P. Wang W. Saville B.R. Havel P.J. Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes.Clin. Transl. Sci. 2011; 4 (21884510): 243-25210.1111/j.1752-8062.2011.00298.xCrossref PubMed Scopus (126) Google Scholar). Comparisons of FPKM data averaged over 24 h between baboon tissues indicate abundant ENHO expression in the central nervous system, particularly in the amygdala and lateral and ventromedial areas of the hypothalamus (VMH) (Fig. 1A). Lower expression levels are observed in liver, kidney (medulla and cortex), ileum, lung, and testes and the pituitary, pineal, and adrenal glands (Fig. 1A). ENHO expression exhibits a predominantly diurnal pattern in most neural and peripheral tissues (Fig. 1B). However, in two areas of the brain exhibiting high expression (amygdala and VMH), expression was observed during both the light and dark periods. Studies in mice indicate liver adropin expression is nutritionally regulated (1Kumar K.G. Trevaskis J.L. Lam D.D. Sutton G.M. Koza R.A. Chouljenko V.N. Kousoulas K.G. Rogers P.M. Kesterson R.A. Thearle M. Ferrante Jr., A.W. Mynatt R.L. Burris T.P. Dong J.Z. Halem H.A. et al.Identification of" @default.
• W2939733089 created "2019-04-25" @default.
• W2939733089 creator A5000914617 @default.
• W2939733089 creator A5013607579 @default.
• W2939733089 creator A5023835049 @default.
• W2939733089 creator A5030753588 @default.
• W2939733089 creator A5033115045 @default.
• W2939733089 creator A5034829692 @default.
• W2939733089 creator A5056635157 @default.
• W2939733089 creator A5074148505 @default.
• W2939733089 creator A5078099225 @default.
• W2939733089 creator A5081546127 @default.
• W2939733089 date "2019-06-01" @default.
• W2939733089 modified "2023-10-13" @default.
• W2939733089 title "Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates" @default.
• W2939733089 cites W1570582509 @default.
• W2939733089 cites W1671430671 @default.
• W2939733089 cites W1723176317 @default.
• W2939733089 cites W1822418086 @default.
• W2939733089 cites W1942254682 @default.
• W2939733089 cites W1963872182 @default.
• W2939733089 cites W1964863686 @default.
• W2939733089 cites W1977040679 @default.
• W2939733089 cites W1989216393 @default.
• W2939733089 cites W1998642050 @default.
• W2939733089 cites W2003544616 @default.
• W2939733089 cites W2012034410 @default.
• W2939733089 cites W2026606203 @default.
• W2939733089 cites W2028009073 @default.
• W2939733089 cites W2045949302 @default.
• W2939733089 cites W2051696948 @default.
• W2939733089 cites W2053585701 @default.
• W2939733089 cites W2054345063 @default.
• W2939733089 cites W2056048638 @default.
• W2939733089 cites W2060889059 @default.
• W2939733089 cites W2061100095 @default.
• W2939733089 cites W2067585219 @default.
• W2939733089 cites W2068647583 @default.
• W2939733089 cites W2072821667 @default.
• W2939733089 cites W2073413674 @default.
• W2939733089 cites W2080035179 @default.
• W2939733089 cites W2087086977 @default.
• W2939733089 cites W2087801348 @default.
• W2939733089 cites W2090841754 @default.
• W2939733089 cites W2090994030 @default.
• W2939733089 cites W2109820081 @default.
• W2939733089 cites W2130410032 @default.
• W2939733089 cites W2145191876 @default.
• W2939733089 cites W2149566550 @default.
• W2939733089 cites W2149688550 @default.
• W2939733089 cites W2155845523 @default.
• W2939733089 cites W2162460759 @default.
• W2939733089 cites W2170971994 @default.
• W2939733089 cites W2186849858 @default.
• W2939733089 cites W2191128990 @default.
• W2939733089 cites W2227482939 @default.
• W2939733089 cites W2259938310 @default.
• W2939733089 cites W2270542660 @default.
• W2939733089 cites W2310386203 @default.
• W2939733089 cites W2320787451 @default.
• W2939733089 cites W2487676344 @default.
• W2939733089 cites W2510170712 @default.
• W2939733089 cites W2529649387 @default.
• W2939733089 cites W2577597748 @default.
• W2939733089 cites W2588994936 @default.
• W2939733089 cites W2603866815 @default.
• W2939733089 cites W2604050818 @default.
• W2939733089 cites W2605659507 @default.
• W2939733089 cites W2610415879 @default.
• W2939733089 cites W2747954651 @default.
• W2939733089 cites W2749122172 @default.
• W2939733089 cites W2755772569 @default.
• W2939733089 cites W2774266172 @default.
• W2939733089 cites W2776764638 @default.
• W2939733089 cites W2783611475 @default.
• W2939733089 cites W2787392047 @default.
• W2939733089 cites W2787429377 @default.
• W2939733089 cites W2790564280 @default.
• W2939733089 cites W2795185096 @default.
• W2939733089 cites W2801379010 @default.
• W2939733089 cites W2802115148 @default.
• W2939733089 cites W2807560776 @default.
• W2939733089 cites W2908505564 @default.
• W2939733089 cites W2914596832 @default.
• W2939733089 cites W2916420000 @default.
• W2939733089 doi "https://doi.org/10.1074/jbc.ra119.007528" @default.
• W2939733089 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6597842" @default.
• W2939733089 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30988006" @default.
• W2939733089 hasPublicationYear "2019" @default.
• W2939733089 type Work @default.
• W2939733089 sameAs 2939733089 @default.
• W2939733089 citedByCount "39" @default.
• W2939733089 countsByYear W29397330892019 @default.
• W2939733089 countsByYear W29397330892020 @default.
• W2939733089 countsByYear W29397330892021 @default.
• W2939733089 countsByYear W29397330892022 @default.
• W2939733089 countsByYear W29397330892023 @default.
• W2939733089 crossrefType "journal-article" @default.

• next