Other
10 Authors
- Iwai N,
- Shen C,
- Ji X,
- Hirokawa G,
- Ma X,
- Weng H,
- Naito Y,
- Takahashi R,
- Endo K,
- Fukushima Y
| First Author | Weng H | Year | 2013 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 304 |
| Issue | 2 | Pages | E187-96 |
| PubMed ID | 23169785 | Mgi Jnum | J:195940 |
| Mgi Id | MGI:5486255 | Doi | 10.1152/ajpendo.00425.2012 |
| Citation | Weng H, et al. (2013) Pex11alpha deficiency impairs peroxisome elongation and division and contributes to nonalcoholic fatty liver in mice. Am J Physiol Endocrinol Metab 304(2):E187-96 |
| abstractText | Hepatic triglyceride (TG) accumulation is considered to be a prerequisite for developing nonalcoholic fatty liver (NAFL). Peroxisomes have many important functions in lipid metabolism, including fatty acid beta-oxidization. However, the pathogenic link between NAFL and peroxisome biogenesis remains unclear. To examine the molecular and physiological functions of the Pex11alpha gene, we disrupted this gene in mice. Body weights and hepatic TG concentrations in Pex11alpha(-/-) mice were significantly higher than those in wild-type (WT) mice fed a normal or a high-fat diet. Hepatic TG concentrations in fasted Pex11alpha(-/-) mice were significantly higher than those in fasted WT mice. Plasma TG levels increased at lower rates in Pex11alpha(-/-) mice than in WT mice after treatment with the lipoprotein lipase inhibitor tyloxapol. The number of peroxisomes was lower in the livers of Pex11alpha(-/-) mice than in those of WT mice. Ultrastructural analysis showed that small and regular spherically shaped peroxisomes were more prevalent in Pex11alpha(-/-) mice fed normal chow supplemented without or with fenofibrate. We observed a significantly higher ratio of empty peroxisomes containing only PMP70, a peroxisome membrane protein, but not catalase, a peroxisome matrix protein, in Pex11alpha(-/-) mice. The mRNA expression levels of peroxisomal fatty acid oxidation-related genes (ATP-binding cassette, subfamily D, member 2, and acyl-CoA thioesterase 3) were significantly higher in WT mice than those in Pex11alpha(-/-) mice under fed conditions. Our results demonstrate that Pex11alpha deficiency impairs peroxisome elongation and abundance and peroxisomal fatty acid oxidation, which contributes to increased lipid accumulation in the liver. |
