| First Author | Bruggeman EC | Year | 2018 |
| Journal | Endocrinology | Volume | 159 |
| Issue | 1 | Pages | 145-162 |
| PubMed ID | 29145563 | Mgi Jnum | J:255505 |
| Mgi Id | MGI:6108049 | Doi | 10.1210/en.2017-00267 |
| Citation | Bruggeman EC, et al. (2018) Neuronal Dnmt1 Deficiency Attenuates Diet-Induced Obesity in Mice. Endocrinology 159(1):145-162 |
| abstractText | Aberrant neuronal DNA methylation patterns have been implicated in the promotion of obesity development; however, the role of neuronal DNA methyltransferases (Dnmts), enzymes that catalyze DNA methylation, in energy balance remains poorly understood. We investigated whether neuronal Dnmt1 regulates normal energy homeostasis and obesity development using a neuronal Dnmt1 knockout (ND1KO) mouse model, Dnmt1fl/fl Synapsin1Cre, which specifically deletes Dnmt1 in neurons. Neuronal Dnmt1 deficiency reduced adiposity in chow-fed mice and attenuated obesity in high-fat diet (HFD)-fed male mice. ND1KO male mice had reduced food intake and increased energy expenditure with the HFD. Furthermore, these mice had improved insulin sensitivity, as measured using an insulin tolerance test. The HFD-fed ND1KO mice had smaller fat pads and upregulation of thermogenic genes in brown adipose tissue. These data suggest that neuronal Dnmt1 plays an important role in regulating energy homeostasis. Notably, ND1KO male mice had elevated estrogen receptor-alpha (ERalpha) gene expression in the medial hypothalamus, which previously has been shown to control body weight. Immunohistochemistry experiments revealed that ERalpha protein expression was upregulated specifically in the dorsomedial region of the ventromedial hypothalamus, a region that might mediate the central effect of leptin. We conclude that neuronal Dnmt1 regulates energy homeostasis through pathways controlling food intake and energy expenditure. In addition, ERalpha expression in the dorsomedial region of the ventromedial hypothalamus might mediate these effects. |
