| First Author | Park MJ | Year | 2024 |
| Journal | Adv Biol (Weinh) | Volume | 8 |
| Issue | 2 | Pages | e2300192 |
| PubMed ID | 38164809 | Mgi Jnum | J:373702 |
| Mgi Id | MGI:8255628 | Doi | 10.1002/adbi.202300192 |
| Citation | Park MJ, et al. (2024) NG,NG-Dimethylarginine Dimethylaminohydrolase 1 Expression Is Dispensable for Cold- or Diet-Induced Thermogenesis. Adv Biol (Weinh) 8(2):e2300192 |
| abstractText | The strategy to activate thermogenic adipocytes has therapeutic potential to overcome obesity as they dissipate surplus energy as heat through various mechanisms. NG,NG-dimethylarginine dimethylaminohydrolases (DDAHs) are enzymes involved in the nitric oxide-protein kinase G signaling axis which increases thermogenic gene expression. However, the role of DDAHs in thermogenic adipocytes has not been elucidated. The adipocyte-specific Ddah1 knockout mice are generated by crossing Ddah1fl/fl mice with adiponectin Cre recombinase mice. Adipocyte-specific DDAH1 overexpressing mice are generated using adeno-associated virus-double-floxed inverse open reading frame (AAV-DIO) system. These mice are analyzed under basal, cold exposure, or high-fat diet (HFD) conditions. Primary inguinal white adipose tissue cells from adipocyte-specific Ddah1 knockout mice expressed comparable amounts of Ucp1 mRNA. Adipocyte-specific DDAH1 overexpressing mice do not exhibit enhanced activation of thermogenic adipocytes. In addition, when these mice are exposed to cold environment or fed an HFD, their body temperature/weight and thermogenesis-related gene and protein expressions are unchanged. These findings indicate that DDAH1 does not play a role in either cold- or diet-induced thermogenesis. Therefore, adipocyte targeting DDAH1 gene therapy for the treatment of obesity is unlikely to be effective. |
