The medio-basal hypothalamic arcuate nucleus (ARC), with its relatively "leaky" blood brain barrier that allows more circulating molecules to enter the brain, has emerged as a key sensor of blood-borne signals. In both the ARC and white adipose tissue (WAT), consumption of a high-fat diet (HFD) rapidly induces infiltration of microglia (ARC) or macrophages (WAT). Animals with HFD-induced obesity (DIO) and insulin resistance additionally accumulate B-lymphocytes in WAT, increasing local production of pathogenic antibodies. We therefore asked whether DIO mice or genetically obese ob/ob mice have increased IgG in the ARC, analogous to the recent observations in WAT. Following 16 weeks exposure to a HFD, WT mice had significantly increased IgG-ir signaling that was specific to the ARC and is exclusively concentrated in microglia. In contrast, IgG-ir of age-matched obese ob/ob mice fed standard chow had ARC IgG levels comparable to those in chow-fed WT control mice. However, following 2 weeks of HFD exposure, ob/ob mice also had a significant increase of IgG-ir in the ARC. In summary, our findings reveal a novel pathophysiological phenomenon specific for the hypothalamic ARC, which is induced by exposure to a HFD and can be enhanced, but not caused, by genetic obesity.
- Received December 23, 2011.
- Accepted February 23, 2012.
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