Year: 2017
Type: article
Abstract: 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.
Source: Nature Communications
DOI: 10.1038/ncomms14556
Institution: University of Washington
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1228426491, G1452187186, Neurocircuits that regulate circadian rhythms, G1948980911, G1985086220, G2298041994, G2337623923, G234089594, G2398048825, Modulating glial-neuronal interactions to treat obesity and diabetes, Cellular Mechanisms of Hypothalamic Inflammation in High Fat Diet-Induced Obesity, G5596841064, G7388217856, G8307212961, G84615435, G8622162125, G882153477, G9000024636, G9000146489, Nutrition Obesity Research Center, Diabetes Research Center, Diabetes, Obesity and Metabolism Training Program
OpenAlex ID: W2590423176