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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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Effect of telmisartan on the reversion of hepatic steatosis, liver mtDNA content, HIF-1α mRNA and protein abundance, and liver 8-isoprostane levels. (A) Liver mtDNA/nDNA ratio assessed by quantitative real-time PCR in each experimental group. *P < 0.029, HFD versus SCD; #P < 0.006, T + HFD versus HFD. (B) HIF-1α mRNA analysed using quantitative real-time PCR in each experimental group. *P < 0.03, HFD versus SCD; #P < 0.0001, T + HFD versus HFD. (C) Liver histology of a representative animal from each experimental group. Haematoxylin and eosin, Masson’s trichrome and osmium tetroxide staining of liver sections at the end of the experiment using a representative rat from each experimental group as described in the ‘Materials and methods’ section. (D) Representative Western blot analysis of liver HIF-1α protein levels in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control. (E) Liver 8-isoprostane levels as a biomarker of local oxidative stress, assessed by ELISA in each experimental group. The results expressed as ng/mg liver protein. *P < 0.004, HFD versus SCD; #P < 0.0001, T + HFD versus HFD, adjusted by liver triglyceride content using ANCOVA. SCD: standard chow diet, HFD: high-fat diet; T + HFD: telmisartan plus high-fat diet.
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fig06: Effect of telmisartan on the reversion of hepatic steatosis, liver mtDNA content, HIF-1α mRNA and protein abundance, and liver 8-isoprostane levels. (A) Liver mtDNA/nDNA ratio assessed by quantitative real-time PCR in each experimental group. *P < 0.029, HFD versus SCD; #P < 0.006, T + HFD versus HFD. (B) HIF-1α mRNA analysed using quantitative real-time PCR in each experimental group. *P < 0.03, HFD versus SCD; #P < 0.0001, T + HFD versus HFD. (C) Liver histology of a representative animal from each experimental group. Haematoxylin and eosin, Masson’s trichrome and osmium tetroxide staining of liver sections at the end of the experiment using a representative rat from each experimental group as described in the ‘Materials and methods’ section. (D) Representative Western blot analysis of liver HIF-1α protein levels in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control. (E) Liver 8-isoprostane levels as a biomarker of local oxidative stress, assessed by ELISA in each experimental group. The results expressed as ng/mg liver protein. *P < 0.004, HFD versus SCD; #P < 0.0001, T + HFD versus HFD, adjusted by liver triglyceride content using ANCOVA. SCD: standard chow diet, HFD: high-fat diet; T + HFD: telmisartan plus high-fat diet.

Mentions: Telmisartan was associated with a significant decrease in the liver mtDNA/nDNA ratio (Fig. 6A) and liver HIF-1α mRNA expression (Fig. 6B). The liver HIF-1α protein level was also decreased in the T + HFD group when compared with the HFD group and SCD group (Fig. 6D). As shown in Figure 6C, fatty liver was efficiently reverted by telmisartan. Interestingly, rats treated with telmisartan showed a significant decrease in liver 8-isoprostane levels when compared with the HFD group (Fig. 6E).


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)

Effect of telmisartan on the reversion of hepatic steatosis, liver mtDNA content, HIF-1α mRNA and protein abundance, and liver 8-isoprostane levels. (A) Liver mtDNA/nDNA ratio assessed by quantitative real-time PCR in each experimental group. *P < 0.029, HFD versus SCD; #P < 0.006, T + HFD versus HFD. (B) HIF-1α mRNA analysed using quantitative real-time PCR in each experimental group. *P < 0.03, HFD versus SCD; #P < 0.0001, T + HFD versus HFD. (C) Liver histology of a representative animal from each experimental group. Haematoxylin and eosin, Masson’s trichrome and osmium tetroxide staining of liver sections at the end of the experiment using a representative rat from each experimental group as described in the ‘Materials and methods’ section. (D) Representative Western blot analysis of liver HIF-1α protein levels in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control. (E) Liver 8-isoprostane levels as a biomarker of local oxidative stress, assessed by ELISA in each experimental group. The results expressed as ng/mg liver protein. *P < 0.004, HFD versus SCD; #P < 0.0001, T + HFD versus HFD, adjusted by liver triglyceride content using ANCOVA. SCD: standard chow diet, HFD: high-fat diet; T + HFD: telmisartan plus high-fat diet.
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Related In: Results  -  Collection

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fig06: Effect of telmisartan on the reversion of hepatic steatosis, liver mtDNA content, HIF-1α mRNA and protein abundance, and liver 8-isoprostane levels. (A) Liver mtDNA/nDNA ratio assessed by quantitative real-time PCR in each experimental group. *P < 0.029, HFD versus SCD; #P < 0.006, T + HFD versus HFD. (B) HIF-1α mRNA analysed using quantitative real-time PCR in each experimental group. *P < 0.03, HFD versus SCD; #P < 0.0001, T + HFD versus HFD. (C) Liver histology of a representative animal from each experimental group. Haematoxylin and eosin, Masson’s trichrome and osmium tetroxide staining of liver sections at the end of the experiment using a representative rat from each experimental group as described in the ‘Materials and methods’ section. (D) Representative Western blot analysis of liver HIF-1α protein levels in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control. (E) Liver 8-isoprostane levels as a biomarker of local oxidative stress, assessed by ELISA in each experimental group. The results expressed as ng/mg liver protein. *P < 0.004, HFD versus SCD; #P < 0.0001, T + HFD versus HFD, adjusted by liver triglyceride content using ANCOVA. SCD: standard chow diet, HFD: high-fat diet; T + HFD: telmisartan plus high-fat diet.
Mentions: Telmisartan was associated with a significant decrease in the liver mtDNA/nDNA ratio (Fig. 6A) and liver HIF-1α mRNA expression (Fig. 6B). The liver HIF-1α protein level was also decreased in the T + HFD group when compared with the HFD group and SCD group (Fig. 6D). As shown in Figure 6C, fatty liver was efficiently reverted by telmisartan. Interestingly, rats treated with telmisartan showed a significant decrease in liver 8-isoprostane levels when compared with the HFD group (Fig. 6E).

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