Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging

Paramita M Ghosh, Zhen Ju Shu, Bing Zhu, Zhongding Lu, Yuji Ikeno, Jeffrey L. Barnes, Chih Ko Yeh, Bin Xian Zhang, Michael S. Katz, Amrita Kamat

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown. Earlier work from our group showed that β-adrenergic receptor (β-AR) levels and β-AR-stimulated adenylyl cyclase activity increase in rat liver during aging. Herewe investigated whether age-associated increases in β-AR signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an increase in hepatic lipid content during senescence and a significant correlation between hepatic fat content and stimulation of adenylyl cyclase activity by the β-AR agonist isoproterenol in rat liver. Isoproterenol administration to young and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in vitro overexpression of β1- and β2-AR subtypes in hepatocytes from young rodents increased cellular lipid content, whereas inhibition of β-ARs by receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was prevented by the β-AR nonselective blocker propranolol, suggesting a novel therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which inhibits adipose tissue lipolysis, did not alter isoproterenolmediated hepatic fat accumulation; thus β-AR responsive hepatic lipid accumulation does not appear to be related primarily to altered lipolysis. These findings suggest that augmented hepatic β-AR signaling during aging may increase lipid accumulation in liver and advocate a possible role for β-adrenergic blockers in preventing or retarding the development of hepatic steatosis.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalJournal of Endocrinology
Volume213
Issue number3
DOIs
StatePublished - Jun 2012

Fingerprint

Adrenergic Receptors
Fats
Liver
Lipids
Isoproterenol
Rodentia
Lipolysis
Adenylyl Cyclases
Hepatocytes
Adrenergic Antagonists
Therapeutic Uses
Fatty Liver
Propranolol
Adipose Tissue

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging. / Ghosh, Paramita M; Shu, Zhen Ju; Zhu, Bing; Lu, Zhongding; Ikeno, Yuji; Barnes, Jeffrey L.; Yeh, Chih Ko; Zhang, Bin Xian; Katz, Michael S.; Kamat, Amrita.

In: Journal of Endocrinology, Vol. 213, No. 3, 06.2012, p. 251-261.

Research output: Contribution to journalArticle

Ghosh, PM, Shu, ZJ, Zhu, B, Lu, Z, Ikeno, Y, Barnes, JL, Yeh, CK, Zhang, BX, Katz, MS & Kamat, A 2012, 'Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging', Journal of Endocrinology, vol. 213, no. 3, pp. 251-261. https://doi.org/10.1530/JOE-11-0406
Ghosh, Paramita M ; Shu, Zhen Ju ; Zhu, Bing ; Lu, Zhongding ; Ikeno, Yuji ; Barnes, Jeffrey L. ; Yeh, Chih Ko ; Zhang, Bin Xian ; Katz, Michael S. ; Kamat, Amrita. / Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging. In: Journal of Endocrinology. 2012 ; Vol. 213, No. 3. pp. 251-261.
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