Review articleInflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration

- Obesity has been linked to neurodegenerative disorders through several mechanisms.
- We review evidence implicating pro-inflammatory cytokines as one possible factor.
- Excess peripheral pro-inflammatory mediators may trigger inflammation in the brain.
- Insulin and insulin-like growth factor 1 (IGF-1) resistance may also contribute.
- Chronic inflammation may exacerbate insulin/IGF-1 signaling defects in the brain.

Obesity is a growing epidemic that contributes to several brain disorders including Alzheimer's, Parkinson's, and Huntington's diseases. Obesity could promote these diseases through several different mechanisms. Here we review evidence supporting the involvement of two recently recognized factors linking obesity with neurodegeneration: the induction of pro-inflammatory cytokines and onset of insulin and insulin-like growth factor 1 (IGF-1) resistance. Excess peripheral pro-inflammatory mediators, some of which can cross the blood brain barrier, may trigger neuroinflammation, which subsequently exacerbates neurodegeneration. Insulin and IGF-1 resistance leads to weakening of neuroprotective signaling by these molecules and can contribute to onset of neurodegenerative diseases.