| First Author | Dorfman MD | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14556 | PubMed ID | 28223698 |
| Mgi Jnum | J:244325 | Mgi Id | MGI:5913104 |
| Doi | 10.1038/ncomms14556 | Citation | Dorfman MD, et al. (2017) Sex differences in microglial CX3CR1 signalling determine obesity susceptibility in mice. Nat Commun 8:14556 |
| abstractText | Female mice are less susceptible to the negative metabolic consequences of high-fat diet feeding than male mice, for reasons that are incompletely understood. Here we identify sex-specific differences in hypothalamic microglial activation via the CX3CL1-CX3CR1 pathway that mediate the resistance of female mice to diet-induced obesity. Female mice fed a high-fat diet maintain CX3CL1-CX3CR1 levels while male mice show reductions in both ligand and receptor expression. Female Cx3cr1 knockout mice develop 'male-like' hypothalamic microglial accumulation and activation, accompanied by a marked increase in their susceptibility to diet-induced obesity. Conversely, increasing brain CX3CL1 levels in male mice through central pharmacological administration or virally mediated hypothalamic overexpression converts them to a 'female-like' metabolic phenotype with reduced microglial activation and body-weight gain. These data implicate sex differences in microglial activation in the modulation of energy homeostasis and identify CX3CR1 signalling as a potential therapeutic target for the treatment of obesity. |
