One of many theories explaining obesity proposes that weight gain is caused by dysfunction of the hypothalamic neurons that regulate energy homeostasis. A possible cause of neuronal dysfunction is inflammation. Obesity is associated with adipose-tissue inflammation; whether the brain is also affected has been unclear. Based on previous observations, Yi et al. examined the brains of mice that had been fed a high-fat diet (HFD) for ∼16 weeks for signs of inflammation. In addition to activated migroglia (the immune cells of the brain), they found an accumulation of IgG specifically in the arcuate nucleus (ARC) of the hypothalamus. This was caused by diet and not obesity per se, because signs of hypothalamic inflammation were not observed in ob/ob mice on a standard diet. The effects of diet on the ARC were rapid, and began to appear as early as 2 weeks after exposure to a HFD. These results provide support that hypothalamic neuropathy promotes diet-induced obesity and suggest that targeting inflammation in the brain might be a promising avenue for therapy. Page 686

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