Hepatic PGC-1α has minor regulatory effect on the liver transcriptome and metabolome during high fat high fructose diet and exercise training
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Hepatic PGC-1α has minor regulatory effect on the liver transcriptome and metabolome during high fat high fructose diet and exercise training. / Rasmussen, Martin Krøyer; Thøgersen, Rebekka; Horsbøl Lindholm, Pernille; Bertram, Hanne Christine; Pilegaard, Henriette.
In: Gene, Vol. 851, 147039, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Hepatic PGC-1α has minor regulatory effect on the liver transcriptome and metabolome during high fat high fructose diet and exercise training
AU - Rasmussen, Martin Krøyer
AU - Thøgersen, Rebekka
AU - Horsbøl Lindholm, Pernille
AU - Bertram, Hanne Christine
AU - Pilegaard, Henriette
N1 - Publisher Copyright: © 2022 The Author(s)
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - CYP
KW - Knock-out
KW - Liver
KW - NAFLD
KW - NMR
KW - Non-alcoholic liver disease
U2 - 10.1016/j.gene.2022.147039
DO - 10.1016/j.gene.2022.147039
M3 - Journal article
C2 - 36368573
AN - SCOPUS:85142204579
VL - 851
JO - Gene
JF - Gene
SN - 0378-1119
M1 - 147039
ER -
ID: 331319842