Cargando…

Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Jadeja, Ravirajsinh N., Jones, Malita A., Fromal, Ollya, Powell, Folami L., Khurana, Sandeep, Singh, Nagendra, Martin, Pamela M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366969/
https://www.ncbi.nlm.nih.gov/pubmed/30659164
http://dx.doi.org/10.18632/aging.101743
_version_ 1783393700886347776
author Jadeja, Ravirajsinh N.
Jones, Malita A.
Fromal, Ollya
Powell, Folami L.
Khurana, Sandeep
Singh, Nagendra
Martin, Pamela M.
author_facet Jadeja, Ravirajsinh N.
Jones, Malita A.
Fromal, Ollya
Powell, Folami L.
Khurana, Sandeep
Singh, Nagendra
Martin, Pamela M.
author_sort Jadeja, Ravirajsinh N.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6366969
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Impact Journals
record_format MEDLINE/PubMed
spelling pubmed-63669692019-02-15 Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis Jadeja, Ravirajsinh N. Jones, Malita A. Fromal, Ollya Powell, Folami L. Khurana, Sandeep Singh, Nagendra Martin, Pamela M. Aging (Albany NY) Research Paper 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. Impact Journals 2019-01-18 /pmc/articles/PMC6366969/ /pubmed/30659164 http://dx.doi.org/10.18632/aging.101743 Text en Copyright © 2019 Jadeja et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Jadeja, Ravirajsinh N.
Jones, Malita A.
Fromal, Ollya
Powell, Folami L.
Khurana, Sandeep
Singh, Nagendra
Martin, Pamela M.
Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis
title Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis
title_full Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis
title_fullStr Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis
title_full_unstemmed Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis
title_short Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis
title_sort loss of gpr109a/hcar2 induces aging-associated hepatic steatosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366969/
https://www.ncbi.nlm.nih.gov/pubmed/30659164
http://dx.doi.org/10.18632/aging.101743
work_keys_str_mv AT jadejaravirajsinhn lossofgpr109ahcar2inducesagingassociatedhepaticsteatosis
AT jonesmalitaa lossofgpr109ahcar2inducesagingassociatedhepaticsteatosis
AT fromalollya lossofgpr109ahcar2inducesagingassociatedhepaticsteatosis
AT powellfolamil lossofgpr109ahcar2inducesagingassociatedhepaticsteatosis
AT khuranasandeep lossofgpr109ahcar2inducesagingassociatedhepaticsteatosis
AT singhnagendra lossofgpr109ahcar2inducesagingassociatedhepaticsteatosis
AT martinpamelam lossofgpr109ahcar2inducesagingassociatedhepaticsteatosis