Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis

Ravirajsinh N. Jadeja, Malita A. Jones, Ollya Fromal, Folami L. Powell, Sandeep Khurana, Nagendra Singh, Pamela M. Martin

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

GPR109A agonists have been used for the treatment of obesity however, the role of GPR109A in regulating aging-associated alterations in lipid metabolism is unknown. In this study we used Gpr109a-/- mice to investigate the effect of aging in the regulation of lipid accumulation. We observed that in mouse and human livers, in addition to Kupffer cells, GPR109A is expressed in hepatocytes. Over 12 months, compared to wild type (WT), Gpr109a-/- mice gained significantly more weight. Food intake and levels of serum lipids were similar among both groups. Compared to age-matched WT mice, 12-months old Gpr109a-/- mice had significantly increased liver weight, hepatic steatosis and serum markers of liver injury. The fatty liver phenotype in Gpr109a-/- mice was associated with increased hepatic expression of lipogenesis genes and decreased expression of lipolysis genes. Gpr109a-/- mice had significantly increased fat tissues, which was associated with significant increase in adipocyte diameter and surface area. Adipose tissue from Gpr109a-/- mice had increased expression of lipogenesis genes; however, expression of lipolytic genes was similar in both groups. Collectively, these results indicate that during aging, GPR109A modulates de novo lipid accumulation in liver and adipose tissue, and its dysregulation can lead to age-associated obesity and hepatic steatosis.

Original languageEnglish (US)
Pages (from-to)386-400
Number of pages15
JournalAging
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2019

Keywords

  • Aging
  • GPR109A
  • Lipid metabolism
  • Steatosis

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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