G6pd2, a gene encoding a glucose-6-phosphate dehydrogenase isoenzyme, is involved in the pentose phosphate pathway (PPP) [1,2,4,8]. The PPP is crucial for generating NADPH, which is essential for fatty acid synthesis, antioxidant defense, and maintaining redox homeostasis. G6pd2 is also associated with lipid metabolism and is expressed in various tissues, with testis-specific expression in post-meiotic spermatogenic cells in mice [9].

In mice after myocardial infarction, increased expression of G6pd2 indicates elevated PPP activity during macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype [1]. In Mortierella alpina, overexpression of G6pd2 significantly enhanced fatty acid synthesis, demonstrating its role in lipogenesis [2]. In irradiated mice, the mRNA levels of G6pd2 in gonadal white adipose tissue were relatively lower, suggesting its potential involvement in radiation-induced fat accumulation [3]. In Canola, G6pd2 was involved in the recovery mechanisms after drought stress and was regulated by drought-responsive miRNAs [4]. In liver-specific pyruvate dehydrogenase complex-deficient (L-PDCKO) male mice, the expression of G6pd2 in the liver was downregulated, while there was an upregulation of lipogenic genes in adipose tissue [5]. In db/db mice treated with catalpol, G6pd2 expression in the liver was differentially regulated, indicating its role in glucose metabolism or insulin signaling pathways [6]. In maize and sorghum roots, G6pd2 was part of the conserved modules in response to nitrate, suggesting its role in nitrogen and carbohydrate metabolism [7]. In soybean roots under drought stress, NO and H2O2 negatively regulated the gene expression of G6pd2, which is a compartmented G6PD-encoding gene [8].

In conclusion, G6pd2 plays important roles in multiple biological processes such as macrophage polarization, lipid and carbohydrate metabolism, and stress responses in different organisms. Mouse models, including those with gene-related manipulations, have provided valuable insights into its functions in processes like fat accumulation, response to stress, and metabolic regulation [1-3,5,7-9].

References:

1. Mouton, Alan J, Aitken, Nikaela M, Moak, Sydney P, McLean, John A, Hall, John E. 2023. Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction. In Frontiers in cardiovascular medicine, 10, 1136252. doi:10.3389/fcvm.2023.1136252. https://pubmed.ncbi.nlm.nih.gov/37215542/

2. Hao, Guangfei, Chen, Haiqin, Gu, Zhennan, Chen, Wei, Chen, Yong Q. 2016. Metabolic Engineering of Mortierella alpina for Enhanced Arachidonic Acid Production through the NADPH-Supplying Strategy. In Applied and environmental microbiology, 82, 3280-3288. doi:10.1128/AEM.00572-16. https://pubmed.ncbi.nlm.nih.gov/27016571/

3. Jo, Sung Kee, Seol, Min-A, Park, Hae-Ran, Jung, Uhee, Roh, Changhyun. 2011. Ionising radiation triggers fat accumulation in white adipose tissue. In International journal of radiation biology, 87, 302-10. doi:10.3109/09553002.2010.537429. https://pubmed.ncbi.nlm.nih.gov/21204617/

4. Pasandideh Arjmand, Maryam, Samizadeh Lahiji, Habibollah, Mohsenzadeh Golfazani, Mohammad, Biglouei, Mohammad Hassan. 2023. Evaluation of protein's interaction and the regulatory network of some drought-responsive genes in Canola under drought and re-watering conditions. In Physiology and molecular biology of plants : an international journal of functional plant biology, 29, 1085-1102. doi:10.1007/s12298-023-01345-1. https://pubmed.ncbi.nlm.nih.gov/37829706/

5. Mahmood, Saleh, Birkaya, Barbara, Rideout, Todd C, Patel, Mulchand S. 2016. Lack of mitochondria-generated acetyl-CoA by pyruvate dehydrogenase complex downregulates gene expression in the hepatic de novo lipogenic pathway. In American journal of physiology. Endocrinology and metabolism, 311, E117-27. doi:10.1152/ajpendo.00064.2016. https://pubmed.ncbi.nlm.nih.gov/27166281/

6. Liu, Jing, Zhang, He-Ran, Hou, Yan-Bao, Song, Xin-Yi, Shen, Xiu-Ping. . Global gene expression analysis in liver of db/db mice treated with catalpol. In Chinese journal of natural medicines, 16, 590-598. doi:10.1016/S1875-5364(18)30096-7. https://pubmed.ncbi.nlm.nih.gov/30197124/

7. Du, Hongyang, Ning, Lihua, He, Bing, Xu, Jinyan, Zhao, Han. 2020. Cross-Species Root Transcriptional Network Analysis Highlights Conserved Modules in Response to Nitrate between Maize and Sorghum. In International journal of molecular sciences, 21, . doi:10.3390/ijms21041445. https://pubmed.ncbi.nlm.nih.gov/32093344/

8. Wang, Xiaomin, Ruan, Mengjiao, Wan, Qi, Yan, Lili, Bi, Yurong. 2019. Nitric oxide and hydrogen peroxide increase glucose-6-phosphate dehydrogenase activities and expression upon drought stress in soybean roots. In Plant cell reports, 39, 63-73. doi:10.1007/s00299-019-02473-3. https://pubmed.ncbi.nlm.nih.gov/31535176/

9. Hendriksen, P J, Hoogerbrugge, J W, Baarends, W M, van der Lende, T, Grootegoed, J A. . Testis-specific expression of a functional retroposon encoding glucose-6-phosphate dehydrogenase in the mouse. In Genomics, 41, 350-9. doi:. https://pubmed.ncbi.nlm.nih.gov/9169132/