Abstract
Mitochondrial biogenesis is an essential process for cell viability. Mice with disruption of the growth hormone receptor (GHR) gene (Ghr gene) in the liver (LiGHRKO), in contrast to long-lived mice with global deletion of the Ghr gene (GHRKO), are characterized by lack of improved insulin sensitivity and severe hepatic steatosis. Tissue-specific disruption of the GHR in liver results in a mouse model with dramatically altered GH/IGF1 axis. We have previously shown increased levels of key regulators of mitochondrial biogenesis in insulin-sensitive GHRKO mice. The aim of the present study is to assess, using real-time PCR, the gene expression of key regulators of mitochondrial biogenesis (Pgc1α, Ampk, Sirt1, Nrf2 and Mfn2) and a marker of mitochondrial activity (CoxIV) in brains, kidneys and livers of male and female LiGHRKO and wild-type (WT) mice. There were significant differences between males and females. In the brain, expression of Pgc1α, Ampk, Sirt1, Nrf2 and Mfn2 was lower in pooled females compared to pooled males. In the kidneys, expression of Ampk and Sirt1 was also lower in female mice. In the liver, no differences between males and females were observed. Sexual dimorphism may play an important role in regulating the biogenesis of mitochondria.
Highlights
The biogenesis of mitochondria is a process by which new mitochondria are formed and is critical for cell viability [1]
Gene expression of key regulators of mitochondrial biogenesis in the brain In the brain, gene expression of Pgc1α, Ampk, Sirt1, Nrf2 and Mfn2 was lower in pooled females than in pooled males (p=0.022, p=0.004, p=0.021, p=0.021, p=0.022, respectively) (Figures 1A-E), demonstrating a significant sex effect
One could envision that similar changes would be detected in the liver of mice with the same genetic intervention limited to the hepatic tissue (LiGHRKO)
Summary
The biogenesis of mitochondria is a process by which new mitochondria are formed and is critical for cell viability [1]. Mitochondria are complex eukaryotic organelles that play a crucial role in energy homeostasis and metabolism. Disruption of mitochondrial biogenesis may lead, via impaired oxidative stress resistance and maintenance of energy production, to the development of numerous degenerative and metabolic diseases [2, 3]. On the contrary, increased level of mitochondrial biogenesis may prevent aging [4]. There are numerous key regulators of mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1 alpha (PGC1α), AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), nuclear respiratory factor 2 (NRF2) and mitofusin 2 (MFN2). Cytochrome c oxidase (COX) is one of the mitochondrial activity markers
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