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• W3046579123 abstract "The micropeptide adropin encoded by the clock-controlled energy homeostasis–associated gene is implicated in the regulation of glucose metabolism. However, its links to rhythms of nutrient intake, energy balance, and metabolic control remain poorly defined. Using surveys of Gene Expression Omnibus data sets, we confirm that fasting suppresses liver adropin expression in lean C57BL/6J (B6) mice. However, circadian rhythm data are inconsistent. In lean mice, caloric restriction (CR) induces bouts of compulsive binge feeding separated by prolonged fasting intervals, increasing NAD-dependent deacetylase sirtuin-1 signaling important for glucose and lipid metabolism regulation. CR up-regulates adropin expression and induces rhythms correlating with cellular stress-response pathways. Furthermore, adropin expression correlates positively with phosphoenolpyruvate carboxokinase-1 (Pck1) expression, suggesting a link with gluconeogenesis. Our previous data suggest that adropin suppresses gluconeogenesis in hepatocytes. Liver-specific adropin knockout (LAdrKO) mice exhibit increased glucose excursions following pyruvate injections, indicating increased gluconeogenesis. Gluconeogenesis is also increased in primary cultured hepatocytes derived from LAdrKO mice. Analysis of circulating insulin levels and liver expression of fasting-responsive cAMP-dependent protein kinase A (PKA) signaling pathways also suggests enhanced responses in LAdrKO mice during a glucagon tolerance test (250 µg/kg intraperitoneally). Fasting-associated changes in PKA signaling are attenuated in transgenic mice constitutively expressing adropin and in fasting mice treated acutely with adropin peptide. In summary, hepatic adropin expression is regulated by nutrient- and clock-dependent extrahepatic signals. CR induces pronounced postprandial peaks in hepatic adropin expression. Rhythms of hepatic adropin expression appear to link energy balance and cellular stress to the intracellular signal transduction pathways that drive the liver fasting response. The micropeptide adropin encoded by the clock-controlled energy homeostasis–associated gene is implicated in the regulation of glucose metabolism. However, its links to rhythms of nutrient intake, energy balance, and metabolic control remain poorly defined. Using surveys of Gene Expression Omnibus data sets, we confirm that fasting suppresses liver adropin expression in lean C57BL/6J (B6) mice. However, circadian rhythm data are inconsistent. In lean mice, caloric restriction (CR) induces bouts of compulsive binge feeding separated by prolonged fasting intervals, increasing NAD-dependent deacetylase sirtuin-1 signaling important for glucose and lipid metabolism regulation. CR up-regulates adropin expression and induces rhythms correlating with cellular stress-response pathways. Furthermore, adropin expression correlates positively with phosphoenolpyruvate carboxokinase-1 (Pck1) expression, suggesting a link with gluconeogenesis. Our previous data suggest that adropin suppresses gluconeogenesis in hepatocytes. Liver-specific adropin knockout (LAdrKO) mice exhibit increased glucose excursions following pyruvate injections, indicating increased gluconeogenesis. Gluconeogenesis is also increased in primary cultured hepatocytes derived from LAdrKO mice. Analysis of circulating insulin levels and liver expression of fasting-responsive cAMP-dependent protein kinase A (PKA) signaling pathways also suggests enhanced responses in LAdrKO mice during a glucagon tolerance test (250 µg/kg intraperitoneally). Fasting-associated changes in PKA signaling are attenuated in transgenic mice constitutively expressing adropin and in fasting mice treated acutely with adropin peptide. In summary, hepatic adropin expression is regulated by nutrient- and clock-dependent extrahepatic signals. CR induces pronounced postprandial peaks in hepatic adropin expression. Rhythms of hepatic adropin expression appear to link energy balance and cellular stress to the intracellular signal transduction pathways that drive the liver fasting response. The human genome contains thousands of short ORFs (sORFs) predicted to encode “micropeptides” of <100 amino acids (1Carvunis A.R. Rolland T. Wapinski I. Calderwood M.A. Yildirim M.A. Simonis N. Charloteaux B. Hidalgo C.A. Barbette J. Santhanam B. Brar G.A. Weissman J.S. Regev A. Thierry-Mieg N. Cusick M.E. et al.Proto-genes and de novo gene birth.Nature. 2012; 487 (22722833): 370-37410.1038/nature11184Crossref PubMed Scopus (305) Google Scholar, 2Saghatelian A. Couso J.P. Discovery and characterization of smORF-encoded bioactive polypeptides.Nat. Chem. Biol. 2015; 11 (26575237): 909-91610.1038/nchembio.1964Crossref PubMed Scopus (109) Google Scholar, 3Khitun A. Ness T.J. Slavoff S.A. Small open reading frames and cellular stress responses.Mol. Omics. 2019; 15 (30810554): 108-11610.1039/c8mo00283eCrossref PubMed Google Scholar). The translation and functions of most have not been studied. Early studies indicate that micropeptides can function as “fine-tuners” of homeostatic processes and are potential leads for developing treatments against the metabolic diseases of obesity (2Saghatelian A. Couso J.P. Discovery and characterization of smORF-encoded bioactive polypeptides.Nat. Chem. Biol. 2015; 11 (26575237): 909-91610.1038/nchembio.1964Crossref PubMed Scopus (109) Google Scholar, 3Khitun A. Ness T.J. Slavoff S.A. Small open reading frames and cellular stress responses.Mol. Omics. 2019; 15 (30810554): 108-11610.1039/c8mo00283eCrossref PubMed Google Scholar, 4Makarewich C.A. Olson E.N. Mining for micropeptides.Trends Cell Biol. 2017; 27 (28528987): 685-69610.1016/j.tcb.2017.04.006Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar). Adropin is a micropeptide translated from a unique highly conserved sORF in mammalian genomes (5Kumar 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 (238) Google Scholar). The 76-amino acid sORF (adropin1–76) is situated in exon 2 of the energy homeostasis–associated (ENHO) gene (5Kumar 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 (238) Google Scholar, 6Ganesh 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 (Silver Spring). 2012; 20 (22318315): 1394-140210.1038/oby.2012.31Crossref PubMed Scopus (154) Google Scholar). Bioinformatic analysis suggest adropin1–33 is a signal peptide targeting the secretory pathway (5Kumar 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 (238) Google Scholar, 7Wang P. Tang W. Li Z. Zou Z. Zhou Y. Li R. Xiong T. Wang J. Zou P. Mapping spatial transcriptome with light-activated proximity-dependent RNA labeling.Nat. Chem. Biol. 2019; 15 (31591565): 1110-111910.1038/s41589-019-0368-5Crossref PubMed Scopus (22) Google Scholar). Adropin34–76 is predicted to be released by proteolysis and is biologically active in rodents and cultured cells (5Kumar 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 (238) Google Scholar, 8Lovren F. Pan Y. Quan A. Singh K.K. Shukla P.C. Gupta M. Al-Omran M. Teoh H. Verma S. Adropin is a novel regulator of endothelial function.Circulation. 2010; 122 (20837912): S185-S19210.1161/CIRCULATIONAHA.109.931782Crossref PubMed Scopus (157) Google Scholar). Experiments using RNAi knockdown suggest the orphan G protein–coupled receptor GPR19 is required for biological responses to adropin34–76 (9Stein L.M. Yosten G.L. Samson W.K. Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19.Am. J. Physiol. Regul. Integr. Comp. Physiol. 2016; 310 (26739651): R476-R48010.1152/ajpregu.00511.2015Crossref PubMed Scopus (34) Google Scholar, 10Rao A. Herr D.R. G protein-coupled receptor GPR19 regulates E-cadherin expression and invasion of breast cancer cells.Biochim. Biophys. Acta Mol. Cell Res. 2017; 1864 (28476646): 1318-132710.1016/j.bbamcr.2017.05.001Crossref PubMed Scopus (26) Google Scholar, 11Thapa 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 (25) Google Scholar). However, the coupling of adropin34–76 with GPR19 is controversial (12Foster S.R. Hauser A.S. Vedel L. Strachan R.T. Huang X.P. Gavin A.C. Shah S.D. Nayak A.P. Haugaard-Kedstrom L.M. Penn R.B. Roth B.L. Brauner-Osborne H. Gloriam D.E. Discovery of human signaling systems: pairing peptides to G protein-coupled receptors.Cell. 2019; 179 (31675498): 895-908.e2110.1016/j.cell.2019.10.010Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar). Yeast two-hybrid protein screens also identified an interaction between adropin30–76 and NB3/Contactin6, a noncanonical membrane-tethered Notch1 ligand, that may regulate neural development (13Wong 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 (48) Google Scholar). The identity, binding, and signal transduction characteristics of cell-surface receptor(s) that mediate adropin's physiological actions remain under investigation. The discovery of adropin was driven by liver transcriptomic data from C57BL/6J (B6) mice (5Kumar 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 (238) Google Scholar). Adropin expression is suppressed by diet-induced or genetically induced obesity at least in part by an increase in miR29b-directed degradation of Enho mRNA (5Kumar 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 (238) Google Scholar, 14Partridge 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 (24) Google Scholar, 15Hung Y.H. Kanke M. Kurtz C.L. Cubitt R. Bunaciu R.P. Miao J. Zhou L. Graham J.L. Hussain M.M. Havel P. Biddinger S. White P.J. Sethupathy P. Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice.Physiol. Genomics. 2019; 51 (31251698): 379-38910.1152/physiolgenomics.00037.2019Crossref PubMed Scopus (11) Google Scholar). The link to miR29b is interesting as the miR29 family also regulates liver lipid metabolism (16Hung Y.H. Kanke M. Kurtz C.L. Cubitt R.L. Bunaciu R.P. Zhou L. White P.J. Vickers K.C. Hussain M.M. Li X. Sethupathy P. MiR-29 regulates de novo lipogenesis in the liver and circulating triglyceride levels in a Sirt1-dependent manner.Front. Physiol. 2019; 10 (31736786): 136710.3389/fphys.2019.01367Crossref PubMed Scopus (4) Google Scholar) and liver insulin sensitivity (17Dooley J. Garcia-Perez J.E. Sreenivasan J. Schlenner S.M. Vangoitsenhoven R. Papadopoulou A.S. Tian L. Schonefeldt S. Serneels L. Deroose C. Staats K.A. Van der Schueren B. De Strooper B. McGuinness O.P. Mathieu C. et al.The microRNA-29 family dictates the balance between homeostatic and pathological glucose handling in diabetes and obesity.Diabetes. 2016; 65 (26696639): 53-6110.2337/db15-0770Crossref PubMed Scopus (82) Google Scholar). Early studies of liver adropin expression identified rapid changes due to energy deficit and food intake (5Kumar 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 (238) Google Scholar). Enho transcription also appears to be controlled by regulatory components of the circadian clock driving rhythms in glucose and lipid metabolism (18Ghoshal 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 (36) Google Scholar). However, the impact of energy balance on liver adropin expression and its significance is controversial. For example, liver adropin expression in teleosts (bony fish) increases with fasting (19Lian A. Wu K. Liu T. Jiang N. Jiang Q. Adropin induction of lipoprotein lipase expression in tilapia hepatocytes.J. Mol. Endocrinol. 2016; 56 (26464334): 11-2210.1530/JME-15-0207Crossref PubMed Scopus (16) Google Scholar). Moreover, whether the sORF encoding adropin is translated in the liver is unclear (13Wong 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 (48) Google Scholar). And whereas caloric restriction (CR) is an energy deficit, it increases plasma adropin concentrations in mice (20Kuhla 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 (45) Google Scholar). Several studies have implicated adropin in the control of glucose metabolism. In mouse and cell-based models, adropin regulates glucose production by the liver and fuel selection (glucose versus fat oxidation) in cardiac and skeletal muscles (5Kumar 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 (238) Google Scholar, 6Ganesh 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 (Silver Spring). 2012; 20 (22318315): 1394-140210.1038/oby.2012.31Crossref PubMed Scopus (154) Google Scholar, 11Thapa 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 (25) Google Scholar, 21Thapa 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): 174-17910.1016/j.yjmcc.2019.02.012Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 22Thapa D. Xie B. Manning J.R. Zhang M. Stoner M.W. Huckestein B.R. Edmunds L.R. Zhang X. Dedousis N.L. O'Doherty R.M. Jurczak M.J. Scott I. Adropin reduces blood glucose levels in mice by limiting hepatic glucose production.Physiol. Rep. 2019; 7 (31004398): e1404310.14814/phy2.14043Crossref PubMed Scopus (18) Google Scholar, 23Gao S. Ghoshal S. Zhang L. Stevens J.R. McCommis K.S. Finck B.N. Lopaschuk G.D. Butler A.A. The peptide hormone adropin regulates signal transduction pathways controlling hepatic glucose metabolism in a mouse model of diet-induced obesity.J. Biol. Chem. 2019; 294 (31324719): 13366-1337710.1074/jbc.RA119.008967Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 24Altamimi T.R. Gao S. Karwi Q.G. Fukushima A. Rawat S. Wagg C.S. Zhang L. Lopaschuk G.D. Adropin regulates cardiac energy metabolism and improves cardiac function and efficiency.Metabolism. 2019; 98 (31202835): 37-4810.1016/j.metabol.2019.06.005Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 25Gao 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 (78) Google Scholar, 26Gao 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 (54) Google Scholar, 27Chen X. Chen S. Shen T. Yang W. Chen Q. Zhang P. You Y. Sun X. Xu H. Tang Y. Mi J. Yang Y. Ling W. Adropin regulates hepatic glucose production via PP2A/AMPK pathway in insulin-resistant hepatocytes.FASEB J. 2020; (32579277)10.1096/fj.202000115rrCrossref Scopus (4) Google Scholar). These results linking adropin to metabolic processes appear clinically relevant. Nonhuman primate (NHP) models are more closely related to humans compared with rodents (28Havel 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 (25) Google Scholar). In rhesus macaques, fasting plasma adropin concentrations correlate with indices of liver glucose and lipid metabolism (29Butler A.A. Zhang J. Price C.A. Stevens J.R. Graham J.L. Stanhope K.L. King S. Krauss R.M. Bremer A.A. Havel P.J. Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates.J. Biol. Chem. 2019; 294 (30988006): 9706-971910.1074/jbc.RA119.007528Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 30Bremer 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 (49) Google Scholar, 31Butler A.A. Graham J.L. Stanhope K.L. Wong S. King S. Bremer A.A. Krauss R.M. Hamilton J. Havel P.J. Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi.J. Lipid Res. 2020; 61 (31919051): 376-38610.1194/jlr.ra119000423Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar). The expression of ENHO in NHP liver suggests daytime peaks that anticipate nutrient intake and co-regulation with enzymes involved in carbohydrate and lipid metabolism (29Butler A.A. Zhang J. Price C.A. Stevens J.R. Graham J.L. Stanhope K.L. King S. Krauss R.M. Bremer A.A. Havel P.J. Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates.J. Biol. Chem. 2019; 294 (30988006): 9706-971910.1074/jbc.RA119.007528Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar). Plasma adropin concentrations in NHP also appear to peak during the daytime (18Ghoshal 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 (36) Google Scholar). Plasma adropin concentrations in NHP correlate with indices of metabolic dysregulation that indicate increased risk for type 2 diabetes and cardiovascular disease in humans (29Butler A.A. Zhang J. Price C.A. Stevens J.R. Graham J.L. Stanhope K.L. King S. Krauss R.M. Bremer A.A. Havel P.J. Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates.J. Biol. Chem. 2019; 294 (30988006): 9706-971910.1074/jbc.RA119.007528Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar). The relationship between plasma adropin concentrations and metabolism in humans is less clear. However, several groups have observed correlations with various indices of glucose and hepatic lipid metabolism (18Ghoshal 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 (36) Google Scholar, 32Butler A.A. Tam C.S. Stanhope K.L. Wolfe B.M. Ali M.R. O'Keeffe M. St-Onge M.P. Ravussin E. Havel P.J. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans.J. Clin. Endocrinol. Metab. 2012; 97 (22872690): 3783-379110.1210/jc.2012-2194Crossref PubMed Scopus (118) Google Scholar, 33Celik 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 (54) Google Scholar, 34St-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 (Silver Spring). 2014; 22: 1056-106310.1002/oby.20631Crossref PubMed Scopus (31) Google Scholar, 35Butler 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 (21) Google Scholar, 36Stevens 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 (Silver Spring). 2016; 24: 1731-174010.1002/oby.21557Crossref PubMed Scopus (21) Google Scholar, 37Chang J.B. Chu N.F. Lin F.H. Hsu J.T. Chen P.Y. Relationship between plasma adropin levels and body composition and lipid characteristics amongst young adolescents in Taiwan.Obes. Res. Clin. Pract. 2018; 12 (28363705): 101-10710.1016/j.orcp.2017.03.001Crossref PubMed Scopus (12) Google Scholar, 38Zang 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: 685-69110.1507/endocrj.EJ18-0060Crossref PubMed Scopus (18) Google Scholar). The current investigation had two objectives. First, open access liver transcriptome (RNA-Seq) data were used to further define the relationship between energy balance, circadian rhythm, and fed-fasting cycles on hepatic Enho expression. Whether the suppression of adropin expression in the liver has a causal relationship with the dysregulation of carbohydrate and lipid metabolism in obesity is not known. Thus, the second objective was to investigate the phenotype of liver-specific adropin knockout (LAdrKO) mice developed using B6 mice with a floxed adropin coding sequence (6Ganesh 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 (Silver Spring). 2012; 20 (22318315): 1394-140210.1038/oby.2012.31Crossref PubMed Scopus (154) Google Scholar). Our prior analysis used housekeeping genes to normalize Enho expression (5Kumar 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 (238) Google Scholar, 18Ghoshal 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 (36) Google Scholar). The technical limitations of using housekeeping genes to normalize gene expression are well-known (39Nolan T. Hands R.E. Bustin S.A. Quantification of mRNA using real-time RT-PCR.Nat. Protoc. 2006; 1 (17406449): 1559-158210.1038/nprot.2006.236Crossref PubMed Scopus (1329) Google Scholar, 40Naoumov N.V. Cyclophilin inhibition as potential therapy for liver diseases.J. Hepatol. 2014; 61 (25048953): 1166-117410.1016/j.jhep.2014.07.008Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar). Open access transcriptomic data (GSE107787) (41Kinouchi K. Magnan C. Ceglia N. Liu Y. Cervantes M. Pastore N. Huynh T. Ballabio A. Baldi P. Masri S. Sassone-Corsi P. Fasting imparts a switch to alternative daily pathways in liver and muscle.Cell Rep. 2018; 25 (30566858): 3299-3314.e610.1016/j.celrep.2018.11.077Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar) verified that a 24-h fast suppresses hepatic Enho expression (Fig. S1A; mean ± S.E. in RPKM for fed, 22.8 ± 1.2; fasted, 7.6 ± 0.7; p < 0.001, n = 18/group). However, whereas our recent data suggest a circadian profile (18Ghoshal 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 (36) Google Scholar), there was no evidence of rhythms in liver Enho expression (Fig. S1B). Whether adropin protein is expressed in the liver is controversial (13Wong 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 (48) Google Scholar). Using GSE73554 (42Atger F. Gobet C. Marquis J. Martin E. Wang J. Weger B. Lefebvre G. Descombes P. Naef F. Gachon F. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver.Proc. Natl. Acad. Sci. U. S. A. 2015; 112 (26554015): E6579-E658810.1073/pnas.1515308112Crossref PubMed Scopus (119) Google Scholar), we profiled liver expression of mature Enho mRNA (Fig. S2A), intronic sequence indicating transcription (Fig. S2B), and mRNA in ribosomal fractions indicating translation (Fig. S2C) over a 24-h period. A modest but significant accumulation of mature Enho mRNA occurred late in the dark period (Fig. S2A), correlating with transcription (Fig. S2B; ρ = 0.534 between intronic and exonic Enho sequence, p < 0.001). Enho sequen" @default.
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• W3046579123 date "2020-10-01" @default.
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• W3046579123 title "Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction" @default.
• W3046579123 cites W1523158326 @default.
• W3046579123 cites W1529337805 @default.
• W3046579123 cites W1570582509 @default.
• W3046579123 cites W1577577364 @default.
• W3046579123 cites W1603786143 @default.
• W3046579123 cites W1932854961 @default.
• W3046579123 cites W1942254682 @default.
• W3046579123 cites W1967395137 @default.
• W3046579123 cites W1969885044 @default.
• W3046579123 cites W1969932710 @default.
• W3046579123 cites W1984849618 @default.
• W3046579123 cites W1991543373 @default.
• W3046579123 cites W1995856733 @default.
• W3046579123 cites W1998642050 @default.
• W3046579123 cites W2008183439 @default.
• W3046579123 cites W2013010460 @default.
• W3046579123 cites W2021597195 @default.
• W3046579123 cites W2022034337 @default.
• W3046579123 cites W2026606203 @default.
• W3046579123 cites W2028009073 @default.
• W3046579123 cites W2028489604 @default.
• W3046579123 cites W2051696948 @default.
• W3046579123 cites W2053073281 @default.
• W3046579123 cites W2060889059 @default.
• W3046579123 cites W2074548049 @default.
• W3046579123 cites W2076417999 @default.
• W3046579123 cites W2080035179 @default.
• W3046579123 cites W2086087714 @default.
• W3046579123 cites W2087086977 @default.
• W3046579123 cites W2107874132 @default.
• W3046579123 cites W2108988707 @default.
• W3046579123 cites W2112941360 @default.
• W3046579123 cites W2113278846 @default.
• W3046579123 cites W2115337061 @default.
• W3046579123 cites W2121061783 @default.
• W3046579123 cites W2127673162 @default.
• W3046579123 cites W2141215872 @default.
• W3046579123 cites W2143687302 @default.
• W3046579123 cites W2147712103 @default.
• W3046579123 cites W2149566550 @default.
• W3046579123 cites W2149688550 @default.
• W3046579123 cites W2152101492 @default.
• W3046579123 cites W2162460759 @default.
• W3046579123 cites W2164135134 @default.
• W3046579123 cites W2166798057 @default.
• W3046579123 cites W2167898988 @default.
• W3046579123 cites W2201283330 @default.
• W3046579123 cites W2223022678 @default.
• W3046579123 cites W2280085712 @default.
• W3046579123 cites W2298500214 @default.
• W3046579123 cites W2319744098 @default.
• W3046579123 cites W2331218777 @default.
• W3046579123 cites W2405221408 @default.
• W3046579123 cites W2510170712 @default.
• W3046579123 cites W2555865797 @default.
• W3046579123 cites W2604050818 @default.
• W3046579123 cites W2611184689 @default.
• W3046579123 cites W2615953964 @default.
• W3046579123 cites W2618417740 @default.
• W3046579123 cites W2743588819 @default.
• W3046579123 cites W2774266172 @default.
• W3046579123 cites W2776764638 @default.
• W3046579123 cites W2795185096 @default.
• W3046579123 cites W2802115148 @default.
• W3046579123 cites W2807560776 @default.
• W3046579123 cites W2892278078 @default.
• W3046579123 cites W2905044900 @default.
• W3046579123 cites W2905460695 @default.
• W3046579123 cites W2913652149 @default.
• W3046579123 cites W2916420000 @default.
• W3046579123 cites W2927163824 @default.
• W3046579123 cites W2939634672 @default.
• W3046579123 cites W2939733089 @default.
• W3046579123 cites W2947105529 @default.
• W3046579123 cites W2951493749 @default.
• W3046579123 cites W2955660432 @default.
• W3046579123 cites W2963740719 @default.
• W3046579123 cites W2964524859 @default.
• W3046579123 cites W2970161534 @default.

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