Pex11a, short for peroxisomal biogenesis factor 11a, is a crucial gene associated with peroxisomes. Peroxisomes play a central role in lipid metabolism, and Pex11a is involved in regulating peroxisome abundance, fatty acid β -oxidation, and de novo lipogenesis [1,2,3]. The gene is also related to the peroxisome proliferator-activated receptor-α (PPARα) signaling pathway [3,4].

Pex11a knockout (Pex11a -/- ) mouse models have been instrumental in understanding its functions. Pex11a -/- mice show increased fat mass, decreased skeletal muscle, higher cholesterol levels, and impaired glucose and insulin tolerance. These mice also consume less oxygen, indicating reduced fatty acid oxidation, along with an accumulation of very long-and long-chain fatty acids [1]. In the kidney, Pex11a deficiency leads to a reduction in the number of functional peroxisomes in proximal tubule cells and aggravates tubulointerstitial lesions in chronic kidney disease models [2].

In conclusion, Pex11a is essential for maintaining normal peroxisome function, lipid metabolism, and energy expenditure. The study of Pex11a knockout mouse models has provided valuable insights into its role in dyslipidaemia, obesity, and chronic kidney disease, highlighting its potential as a therapeutic target for these diseases [1,2].

References:

1. Chen, Congcong, Wang, Hongwei, Chen, Bicheng, Weng, Huachun, Cai, Lu. 2018. Pex11a deficiency causes dyslipidaemia and obesity in mice. In Journal of cellular and molecular medicine, 23, 2020-2031. doi:10.1111/jcmm.14108. https://pubmed.ncbi.nlm.nih.gov/30585412/

2. Weng, Huachun, Ji, Xu, Endo, Kosuke, Iwai, Naoharu. 2014. Pex11a deficiency is associated with a reduced abundance of functional peroxisomes and aggravated renal interstitial lesions. In Hypertension (Dallas, Tex. : 1979), 64, 1054-60. doi:10.1161/HYPERTENSIONAHA.114.04094. https://pubmed.ncbi.nlm.nih.gov/25113963/

3. Weng, Huachun, Endo, Kosuke, Li, Jiawei, Kito, Naoko, Iwai, Naoharu. 2015. Induction of peroxisomes by butyrate-producing probiotics. In PloS one, 10, e0117851. doi:10.1371/journal.pone.0117851. https://pubmed.ncbi.nlm.nih.gov/25659146/

4. Rolver, Michala G, Holland, Lya K K, Ponniah, Muthulakshmi, Sandelin, Albin, Pedersen, Stine Falsig. 2023. Chronic acidosis rewires cancer cell metabolism through PPARα signaling. In International journal of cancer, 152, 1668-1684. doi:10.1002/ijc.34404. https://pubmed.ncbi.nlm.nih.gov/36533672/