Dipeptidyl peptidase IV in the hypothalamus and hippocampus of monosodium glutamate obese and food-deprived rats.
Proline-specific dipeptidyl peptidases are emerging as a protease family with important roles in the regulation of signaling by peptide hormones related to energy balance. The treatment of neonatal rats with monosodium glutamate (MSG) is known to produce a selective damage on the arcuate nucleus with development of obesity. This study investigates the relationship among dipeptidyl peptidase IV (DPPIV) hydrolyzing activity, CD26 protein, fasting, and MSG model of obesity in 2 areas of the central nervous system. Dipeptidyl peptidase IV and CD26 were, respectively, evaluated by fluorometry, and enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction in soluble (SF) and membrane-bound (MF) fractions from the hypothalamus and hippocampus of MSG-treated and normal rats, submitted or not to food deprivation (FD). Dipeptidyl peptidase IV in both areas was distinguished kinetically as insensitive (DI) and sensitive (DS) to diprotin A. Compared with the controls, MSG and/or FD decreased the activity of DPPIV-DI in the SF and MF from the hypothalamus, as well as the activity of DPPIV-DS in the SF from the hypothalamus and in the MF from the hippocampus. Monosodium glutamate and/or FD increased the activity of DPPIV-DI in the MF from the hippocampus. The monoclonal protein expression of membrane CD26 by enzyme-linked immunosorbent assay decreased in the hypothalamus and increased in the hippocampus of MSG and/or FD relative to the controls. The existence of DPPIV-like activity with different sensitivities to diprotin A and the identity of insensitive with CD26 were demonstrated for the first time in the central nervous system. Data also demonstrated the involvement of DPPIV-DI/CD26 hydrolyzing activity in the energy balance probably through the regulation of neuropeptide Y and β-endorphin levels in the hypothalamus and hippocampus.
Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brazil.
Rafaela Fadoni
RF
Alponti
Rodrigo
R
Frezzatti
Juliana Marton
JM
Barone
Valter de Sousa
Vde S
Alegre
Paulo Flavio
PF
Silveira
D000818:Animals; D000831:Animals, Newborn; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D005215:Fasting / Q000378:metabolism*; D005508:Food Deprivation; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D012970:Sodium Glutamate / Q000494:pharmacology
D018819:Dipeptidyl Peptidase 4; D012970:Sodium Glutamate