Glucagon-like peptide-2 reduces the obesity associated inflammation in brain

Growing evidence suggests a link between obesity and neurodegeneration. The purpose of the present study was
to explore the neuroprotective potential of glucagon-like peptide-2 (GLP-2) in the brain of high fat diet (HFD)-
fed mice. Markers of inflammation and oxidative stress were analysed in the brains of obese mice chronically
treated with [Gly2]-GLP-2 (teduglutide), the stable analogue of the GLP-2, and they were compared to agematched
untreated obese and lean animals. Neurodegeneration was examined by TUNEL assay. HFD feeding
increased the expression of pro-inflammatory mediators (NF-kB, IL-8, TNF-?, IL-1? and IL-6), glial fibrillary
acidic protein (GFAP), index of gliosis and neurodegeneration, stress marker proteins (p-ERK, Hsp60 and i-NOS),
amyloid-? precursor protein (APP). [Gly2]-GLP-2 treatment significantly attenuated the HFD-induced increased
expression of the various markers, as well as the higher levels of reactive oxygen species found in brains of
untreated-HFD mice. Immunofluorescence confirmed that the increase of GFAP or APP in the brain cortex of
HFD mice were less prominent in the [Gly2]-GLP-2 treated group. TUNEL-positive cell number in brain sections
of [Gly2]-GLP-2-treated HFD-fed mice was significantly lesser in comparison with untreated-HFD animals and
similar to STD fed mice. In conclusion, the results of the present study suggest that GLP-2 stable analogue
improves the obesity-associated neuroinflammation and the central stress conditions, it reduces the neuronal
apoptotic death, providing evidence for a neuroprotective role of the peptide.