Altered expression of hepatic β-adrenergic receptors in aging rats: Implications for age-related metabolic dysfunction in liver

Yun Shi, Zhen Ju Shu, Hanzhou Wang, Jeffrey L. Barnes, Chih Ko Yeh, Paramita M. Ghosh, Michael S. Katz, Amrita Kamat

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Increased β-adrenergic receptor (β-AR)-mediated activation of adenylyl cyclase (AC) in rat liver during aging has been linked to age-related increases in hepatic glucose output and hepatosteatosis. In this study, we investigated the expression of β-ARs, individual receptor subtypes, and G protein-coupled receptor (GPCR) regulatory proteins in livers from aging rats. Radioli-gand-binding studies demonstrated that β-AR density increased by greater than threefold in hepatocyte membranes from senescent (24-mo-old) compared with young adult (7-mo-old) rats and that this phenomenon was blocked by food restriction, which is known to retard aging processes in rodents. Competition-binding studies revealed a mixed population of β1- and β2-AR subtypes in liver membranes over the adult life span, with a trend for greater β2-AR density with age. Expression of both β-AR subtype mRNAs in rat liver increased with age, whereas β2- but not β1-AR protein levels declined in livers of old animals. Immunoreactive β2- but not β1-ARs were preferentially distributed in pericentral hepatic regions. Levels of GRK2/3 and β-arrestin 2 proteins, which are involved in downregulation of agonist-activated GPCRs, including β-ARs, increased during aging. Insofar as sympathetic tone increases with age, our findings suggest that, despite enhanced agonist-mediated downregulation of hepatic β-ARs preferentially affecting the β2-AR subtype, increased generation of both receptor subtypes during aging augments the pool of plasma membrane-bound β-ARs coupled to AC in hepatocytes. This study thus identifies one or both β-AR subtypes as possible therapeutic targets involved in aberrant hepatic processes of glucose and lipid metabolism during aging.

Original languageEnglish (US)
Pages (from-to)R574-R583
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume314
Issue number4
DOIs
StatePublished - Apr 16 2018

Keywords

  • Food restriction
  • G protein-coupled receptor
  • G protein-coupled receptor serine/threonine kinase
  • Hepatocytes
  • β-arrestin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Altered expression of hepatic β-adrenergic receptors in aging rats: Implications for age-related metabolic dysfunction in liver'. Together they form a unique fingerprint.

  • Cite this