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High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia.

Carabelli J, Burgueño AL, Rosselli MS, Gianotti TF, Lago NR, Pirola CJ, Sookoian S - J. Cell. Mol. Med. (2010)

Bottom Line: The liver mtDNA/nDNA ratio significantly correlated with the hepatic expression of HIF-1α mRNA (R: 0.37, P < 0.001); liver HIF-1α mRNA was significantly higher in the HFD group.The hepatic expression of mRNA of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PGC-1β, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor δ and Tfam, was not associated with the liver mtDNA content.In conclusion, we found that HFD promotes an increase in liver mitochondrial biogenesis in response to hypoxia via HIF-1α, probably to enhance the mitochondrial function as well as to accommodate the metabolic load.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.

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(A) Liver expression analysis of HIF-1α mRNA by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. In each sample, the gene expression was normalized to the expression of cyclophilin A and multiplied by 100. (B) Representative Western blot analysis of liver HIF-1α protein expression in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control.
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fig03: (A) Liver expression analysis of HIF-1α mRNA by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. In each sample, the gene expression was normalized to the expression of cyclophilin A and multiplied by 100. (B) Representative Western blot analysis of liver HIF-1α protein expression in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control.

Mentions: To address the question of whether the increase in liver mtDNA copy number is associated with HIF-1α, we examined the liver expression of HIF-1α mRNA, and observed a significant positive correlation between liver mtDNA/nDNA ratio and hepatic levels of HIF-1α mRNA (R: 0.37, P < 0.001). We found that the level of HIF-1α mRNA was significantly higher in the HFD group (Fig. 3A). Western blot analysis showed that the level of protein, in parallel with the liver mRNA HIF-1α expression, was also significantly higher in the livers with increased mtDNA/nDNA ratio (Fig. 3B).


High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia.

Carabelli J, Burgueño AL, Rosselli MS, Gianotti TF, Lago NR, Pirola CJ, Sookoian S - J. Cell. Mol. Med. (2010)

(A) Liver expression analysis of HIF-1α mRNA by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. In each sample, the gene expression was normalized to the expression of cyclophilin A and multiplied by 100. (B) Representative Western blot analysis of liver HIF-1α protein expression in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373333&req=5

fig03: (A) Liver expression analysis of HIF-1α mRNA by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. In each sample, the gene expression was normalized to the expression of cyclophilin A and multiplied by 100. (B) Representative Western blot analysis of liver HIF-1α protein expression in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control.
Mentions: To address the question of whether the increase in liver mtDNA copy number is associated with HIF-1α, we examined the liver expression of HIF-1α mRNA, and observed a significant positive correlation between liver mtDNA/nDNA ratio and hepatic levels of HIF-1α mRNA (R: 0.37, P < 0.001). We found that the level of HIF-1α mRNA was significantly higher in the HFD group (Fig. 3A). Western blot analysis showed that the level of protein, in parallel with the liver mRNA HIF-1α expression, was also significantly higher in the livers with increased mtDNA/nDNA ratio (Fig. 3B).

Bottom Line: The liver mtDNA/nDNA ratio significantly correlated with the hepatic expression of HIF-1α mRNA (R: 0.37, P < 0.001); liver HIF-1α mRNA was significantly higher in the HFD group.The hepatic expression of mRNA of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PGC-1β, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor δ and Tfam, was not associated with the liver mtDNA content.In conclusion, we found that HFD promotes an increase in liver mitochondrial biogenesis in response to hypoxia via HIF-1α, probably to enhance the mitochondrial function as well as to accommodate the metabolic load.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.

Show MeSH
Related in: MedlinePlus