Hepatic PGC-1α has minor regulatory effect on the liver transcriptome and metabolome during high fat high fructose diet and exercise training

Hepatic PGC-1α has minor regulatory effect on the liver transcriptome and metabolome during high fat high fructose diet and exercise training

[Display omitted] •High fat high fructose diet has major impact on the transcriptome.•Hepatic PGC-1α is not essential for the HFFD induced transcriptome and metabolome.•HFFD combined with exercise only induced limited gene regulation compared to HFFD.•HFFD induced increased expression of Cyp2a4, Cyp...

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Published in:Gene Vol. 851; p. 147039
Main Authors: Rasmussen, Martin Krøyer, Thøgersen, Rebekka, Horsbøl Lindholm, Pernille, Bertram, Hanne Christine, Pilegaard, Henriette
Format: Journal Article
Language:English
Published: Elsevier B.V 30-01-2023
Subjects:
CYP
Knock-out
Liver
NAFLD
NMR
Non-alcoholic liver disease
T2DM
NAFLD
HNF-4α
Non-alcoholic liver disease
Liver
HFD
PGC-1α
PXR
PPARα
FOXO1
PPARγ
HFFD+Ex
PCA
NMR
TG
CAR
FDR
Sirt1
CYP
HFFD
Knock-out
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Summary:[Display omitted] •High fat high fructose diet has major impact on the transcriptome.•Hepatic PGC-1α is not essential for the HFFD induced transcriptome and metabolome.•HFFD combined with exercise only induced limited gene regulation compared to HFFD.•HFFD induced increased expression of Cyp2a4, Cyp2c29, Cyp2e1 and Cyp3a11. The prevalence of non-alcoholic fatty liver diseases (NAFLD) has reached epidemic levels during recent years and a major driver of NAFLD are diets high in fat and fructose. A common practice in the treatment of NAFLD are life-style interventions including for example increased physical activity. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) has been shown to be central in mediating the beneficial effects of exercise training by regulating the expression of key metabolic genes. However, the significance of hepatic PGC-1α for high fat high fructose (HFFD) induced changes in gene expression and metabolites associated with NAFLD has not been elucidated. Therefore the aim of the present study was to investigate the effect of hepatic PGC-1α on HFFD and exercise-induced changes in the hepatic transcriptome and metabolome in mice. Using gene-arrays and 1H NMR spectroscopy, the liver transcriptome and metabolome of liver-specific PGC-1α knock-out mice receiving either standard chow, HFFD or HFFD + exercise (HFFD + Ex) were determined. In total 122 genes were identified as differently expressed in mice receiving HFFD for 13 weeks compared to chow, while the loss of hepatic PGC-1α only had very minor effects on the transcriptome. The same was observed for the liver metabolome. The effect of 4 weeks exercise training in combination with 13 weeks of HFFD, had small effects on the transcriptome and metabolome compared to HFFD alone. Together our results highlight a minor regulatory effect of hepatic PGC-1α on the liver transcriptome during high fat high fructose diet and exercise training.
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ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2022.147039