Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding.
PGC-1β plays pleiotropic roles in regulating intermediary metabolism and has been shown to regulate both catabolic and anabolic processes in liver. We sought to evaluate the effects of PGC-1β on liver energy metabolism by generating mice with postnatal, liver-specific deletion of PGC-1β (LS-PGC-1β(-...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3532159?pdf=render |
id |
doaj-41a6eb0a8f81449aafbbfd489e7e2aa4 |
---|---|
record_format |
Article |
spelling |
doaj-41a6eb0a8f81449aafbbfd489e7e2aa42020-11-25T00:23:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5264510.1371/journal.pone.0052645Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding.Kari T ChambersZhouji ChenPeter A CrawfordXiaorong FuShawn C BurgessLing LaiTeresa C LeoneDaniel P KellyBrian N FinckPGC-1β plays pleiotropic roles in regulating intermediary metabolism and has been shown to regulate both catabolic and anabolic processes in liver. We sought to evaluate the effects of PGC-1β on liver energy metabolism by generating mice with postnatal, liver-specific deletion of PGC-1β (LS-PGC-1β(-/-) mice). LS-PGC-1β(-/-) mice were outwardly normal, but exhibited a significant increase in hepatic triglyceride content at 6 weeks of age. Hepatic steatosis was due, at least in part, to impaired capacity for fatty acid oxidation and marked mitochondrial dysfunction. Mitochondrial DNA content and the expression of genes encoding multiple steps in mitochondrial fatty acid oxidation and oxidative phosphorylation pathways were significantly diminished in LS-PGC-1β(-/-) mice. Liquid chromatography mass spectrometry-based analyses also revealed that acetylcarnitine and butyrylcarnitine levels were depleted whereas palmitoylcarnitine content was increased in LS-PGC-1β(-/-) liver, which is consistent with attenuated rates of fatty acid oxidation. Interestingly, loss of PGC-1β also significantly impaired inducible expression of glycolytic and lipogenic enzymes that occurs with high carbohydrate diet refeeding after a prolonged fast. These results suggest that PGC-1β plays dual roles in regulating hepatic fatty acid metabolism by controlling the expression of programs of genes involved in both fatty acid oxidation and de novo fatty acid synthesis.http://europepmc.org/articles/PMC3532159?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kari T Chambers Zhouji Chen Peter A Crawford Xiaorong Fu Shawn C Burgess Ling Lai Teresa C Leone Daniel P Kelly Brian N Finck |
spellingShingle |
Kari T Chambers Zhouji Chen Peter A Crawford Xiaorong Fu Shawn C Burgess Ling Lai Teresa C Leone Daniel P Kelly Brian N Finck Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. PLoS ONE |
author_facet |
Kari T Chambers Zhouji Chen Peter A Crawford Xiaorong Fu Shawn C Burgess Ling Lai Teresa C Leone Daniel P Kelly Brian N Finck |
author_sort |
Kari T Chambers |
title |
Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. |
title_short |
Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. |
title_full |
Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. |
title_fullStr |
Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. |
title_full_unstemmed |
Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. |
title_sort |
liver-specific pgc-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
PGC-1β plays pleiotropic roles in regulating intermediary metabolism and has been shown to regulate both catabolic and anabolic processes in liver. We sought to evaluate the effects of PGC-1β on liver energy metabolism by generating mice with postnatal, liver-specific deletion of PGC-1β (LS-PGC-1β(-/-) mice). LS-PGC-1β(-/-) mice were outwardly normal, but exhibited a significant increase in hepatic triglyceride content at 6 weeks of age. Hepatic steatosis was due, at least in part, to impaired capacity for fatty acid oxidation and marked mitochondrial dysfunction. Mitochondrial DNA content and the expression of genes encoding multiple steps in mitochondrial fatty acid oxidation and oxidative phosphorylation pathways were significantly diminished in LS-PGC-1β(-/-) mice. Liquid chromatography mass spectrometry-based analyses also revealed that acetylcarnitine and butyrylcarnitine levels were depleted whereas palmitoylcarnitine content was increased in LS-PGC-1β(-/-) liver, which is consistent with attenuated rates of fatty acid oxidation. Interestingly, loss of PGC-1β also significantly impaired inducible expression of glycolytic and lipogenic enzymes that occurs with high carbohydrate diet refeeding after a prolonged fast. These results suggest that PGC-1β plays dual roles in regulating hepatic fatty acid metabolism by controlling the expression of programs of genes involved in both fatty acid oxidation and de novo fatty acid synthesis. |
url |
http://europepmc.org/articles/PMC3532159?pdf=render |
work_keys_str_mv |
AT karitchambers liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT zhoujichen liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT peteracrawford liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT xiaorongfu liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT shawncburgess liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT linglai liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT teresacleone liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT danielpkelly liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding AT briannfinck liverspecificpgc1betadeficiencyleadstoimpairedmitochondrialfunctionandlipogenicresponsetofastingrefeeding |
_version_ |
1725355859047874560 |