Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis

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

Research output: Contribution to journalArticle

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

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Liver
Lipogenesis
Lipids
Gene Expression
Adipose Tissue
Obesity
Weights and Measures
Kupffer Cells
Lipolysis
Fatty Liver
Lipid Metabolism
Adipocytes
Hepatocytes
Eating
Biomarkers
Fats
Phenotype
Wounds and Injuries
Serum
Genes

Keywords

  • Aging
  • GPR109A
  • Lipid metabolism
  • Steatosis

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Jadeja, R. N., Jones, M. A., Fromal, O., Powell, F. L., Khurana, S., Singh, N., & Martin, P. M. (2019). Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis. Aging, 11(2), 386-400. https://doi.org/10.18632/aging.101743

Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis. / Jadeja, Ravirajsinh N.; Jones, Malita A.; Fromal, Ollya; Powell, Folami Lamoke; Khurana, Sandeep; Singh, Nagendra; Martin, Pamela Moore.

In: Aging, Vol. 11, No. 2, 01.01.2019, p. 386-400.

Research output: Contribution to journalArticle

Jadeja, RN, Jones, MA, Fromal, O, Powell, FL, Khurana, S, Singh, N & Martin, PM 2019, 'Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis' Aging, vol. 11, no. 2, pp. 386-400. https://doi.org/10.18632/aging.101743
Jadeja RN, Jones MA, Fromal O, Powell FL, Khurana S, Singh N et al. Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis. Aging. 2019 Jan 1;11(2):386-400. https://doi.org/10.18632/aging.101743
Jadeja, Ravirajsinh N. ; Jones, Malita A. ; Fromal, Ollya ; Powell, Folami Lamoke ; Khurana, Sandeep ; Singh, Nagendra ; Martin, Pamela Moore. / Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis. In: Aging. 2019 ; Vol. 11, No. 2. pp. 386-400.
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