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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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Left panel: Liver histology of a representative animal from each experimental group. Haematoxylin and eosin (A and B), Masson’s trichrome (C and D), and osmium tetroxide (E and F) staining of liver sections at the end of the experiment. The livers of rats fed with SCD show normal histology and absence of fat accumulation. The livers of rats fed with HFD show severe panlobular micro and macrovesicular steatosis. Arrows indicate large or small droplet steatosis, and lipid globules appear black after osmium tetroxide staining (F). Original magnification: 400×. (G) Quantitative evaluation of steatosis score. Steatosis was given a score from 0 to 3 as described in the ‘Materials and methods’ section. The data are presented as mean ± S.E. (H) Biochemical analysis of hepatic triglyceride content. The results (μg/mg liver) are expressed as mean ± S.E.
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fig01: Left panel: Liver histology of a representative animal from each experimental group. Haematoxylin and eosin (A and B), Masson’s trichrome (C and D), and osmium tetroxide (E and F) staining of liver sections at the end of the experiment. The livers of rats fed with SCD show normal histology and absence of fat accumulation. The livers of rats fed with HFD show severe panlobular micro and macrovesicular steatosis. Arrows indicate large or small droplet steatosis, and lipid globules appear black after osmium tetroxide staining (F). Original magnification: 400×. (G) Quantitative evaluation of steatosis score. Steatosis was given a score from 0 to 3 as described in the ‘Materials and methods’ section. The data are presented as mean ± S.E. (H) Biochemical analysis of hepatic triglyceride content. The results (μg/mg liver) are expressed as mean ± S.E.

Mentions: HFD-fed rats developed severe hepatic microvesicular and macrovesicular steatosis (Fig. 1). As shown in Figure 1G, quantitative evaluation of steatosis score from haematoxylin and eosin and osmium tetroxide staining of liver sections at the end of the experiment demonstrated significant differences between the groups (ancova with steatosis gradation as a categorical response variable with ordinal multinomial distribution and probit as a link function, with animal length and adipose tissue as continuous predictor variables). This finding was confirmed by biochemical analysis of hepatic triglyceride content (Fig. 1H).


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)

Left panel: Liver histology of a representative animal from each experimental group. Haematoxylin and eosin (A and B), Masson’s trichrome (C and D), and osmium tetroxide (E and F) staining of liver sections at the end of the experiment. The livers of rats fed with SCD show normal histology and absence of fat accumulation. The livers of rats fed with HFD show severe panlobular micro and macrovesicular steatosis. Arrows indicate large or small droplet steatosis, and lipid globules appear black after osmium tetroxide staining (F). Original magnification: 400×. (G) Quantitative evaluation of steatosis score. Steatosis was given a score from 0 to 3 as described in the ‘Materials and methods’ section. The data are presented as mean ± S.E. (H) Biochemical analysis of hepatic triglyceride content. The results (μg/mg liver) are expressed as mean ± S.E.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4373333&req=5

fig01: Left panel: Liver histology of a representative animal from each experimental group. Haematoxylin and eosin (A and B), Masson’s trichrome (C and D), and osmium tetroxide (E and F) staining of liver sections at the end of the experiment. The livers of rats fed with SCD show normal histology and absence of fat accumulation. The livers of rats fed with HFD show severe panlobular micro and macrovesicular steatosis. Arrows indicate large or small droplet steatosis, and lipid globules appear black after osmium tetroxide staining (F). Original magnification: 400×. (G) Quantitative evaluation of steatosis score. Steatosis was given a score from 0 to 3 as described in the ‘Materials and methods’ section. The data are presented as mean ± S.E. (H) Biochemical analysis of hepatic triglyceride content. The results (μg/mg liver) are expressed as mean ± S.E.
Mentions: HFD-fed rats developed severe hepatic microvesicular and macrovesicular steatosis (Fig. 1). As shown in Figure 1G, quantitative evaluation of steatosis score from haematoxylin and eosin and osmium tetroxide staining of liver sections at the end of the experiment demonstrated significant differences between the groups (ancova with steatosis gradation as a categorical response variable with ordinal multinomial distribution and probit as a link function, with animal length and adipose tissue as continuous predictor variables). This finding was confirmed by biochemical analysis of hepatic triglyceride content (Fig. 1H).

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