[HTML][HTML] Obesity is associated with hypothalamic injury in rodents and humans

JP Thaler, CX Yi, EA Schur, SJ Guyenet… - The Journal of …, 2012 - Am Soc Clin Investig
JP Thaler, CX Yi, EA Schur, SJ Guyenet, BH Hwang, MO Dietrich, X Zhao, DA Sarruf, V Izgur…
The Journal of clinical investigation, 2012Am Soc Clin Investig
Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by
inflammation both in peripheral tissues and in hypothalamic areas critical for energy
homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops
as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats
and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both
reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic …
Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding. Although these responses temporarily subsided, suggesting that neuroprotective mechanisms may initially limit the damage, with continued HFD feeding, inflammation and gliosis returned permanently to the mediobasal hypothalamus. Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI. These findings collectively suggest that, in both humans and rodent models, obesity is associated with neuronal injury in a brain area crucial for body weight control.
The Journal of Clinical Investigation