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Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction.

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Title: Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction.
Authors: Banerjee, Subhashis1, Ghoshal, Sarbani1, Stevens, Joseph R.1, McCommis, Kyle S.2,3,4, Gao, Su5, Castro-Sepulveda, Mauricio6, Mizgier, Maria L.7, Girardet, Clemence1, Ganesh Kumar, K.5, Galgani, Jose E.7, Niehoff, Michael L.8,9,10, Farr, Susan A.8,9,10, Jinsong Zhang1, Butler, Andrew A.1,5,8 andrew.butler@health.slu.edu
Source: Journal of Biological Chemistry. 10/2/2020, Vol. 295 Issue 40, p13753-13768. 23p.
Subjects: Low-calorie diet, Cyclic-AMP-dependent protein kinase, Sirtuins, Metabolic regulation, Transgenic mice, Liver, Calretinin
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. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction.
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  Data: <searchLink fieldCode="AR" term="%22Banerjee%2C+Subhashis%22">Banerjee, Subhashis</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ghoshal%2C+Sarbani%22">Ghoshal, Sarbani</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Stevens%2C+Joseph+R%2E%22">Stevens, Joseph R.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22McCommis%2C+Kyle+S%2E%22">McCommis, Kyle S.</searchLink><relatesTo>2,3,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Gao%2C+Su%22">Gao, Su</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Castro-Sepulveda%2C+Mauricio%22">Castro-Sepulveda, Mauricio</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Mizgier%2C+Maria+L%2E%22">Mizgier, Maria L.</searchLink><relatesTo>7</relatesTo><br /><searchLink fieldCode="AR" term="%22Girardet%2C+Clemence%22">Girardet, Clemence</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ganesh+Kumar%2C+K%2E%22">Ganesh Kumar, K.</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Galgani%2C+Jose+E%2E%22">Galgani, Jose E.</searchLink><relatesTo>7</relatesTo><br /><searchLink fieldCode="AR" term="%22Niehoff%2C+Michael+L%2E%22">Niehoff, Michael L.</searchLink><relatesTo>8,9,10</relatesTo><br /><searchLink fieldCode="AR" term="%22Farr%2C+Susan+A%2E%22">Farr, Susan A.</searchLink><relatesTo>8,9,10</relatesTo><br /><searchLink fieldCode="AR" term="%22Jinsong+Zhang%22">Jinsong Zhang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Butler%2C+Andrew+A%2E%22">Butler, Andrew A.</searchLink><relatesTo>1,5,8</relatesTo><i> andrew.butler@health.slu.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 10/2/2020, Vol. 295 Issue 40, p13753-13768. 23p.
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– Name: Abstract
  Label: Abstract
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1074/jbc.RA120.014381
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        Text: English
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        PageCount: 23
        StartPage: 13753
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      – SubjectFull: Low-calorie diet
        Type: general
      – SubjectFull: Cyclic-AMP-dependent protein kinase
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      – SubjectFull: Sirtuins
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      – SubjectFull: Metabolic regulation
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      – SubjectFull: Transgenic mice
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      – SubjectFull: Liver
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      – SubjectFull: Calretinin
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              Text: 10/2/2020
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