Abstract
The prevalence of obesity is rapidly increasing across the world. Physiological alterations associated with obesity are known to alter enzymes expression and/or activities. As drug-metabolizing and antioxidant enzymes serve as defense system against potentially toxic compounds, their modulation might have serious consequences. Here we studied selected antioxidant and drug metabolizing enzymes (DME) in monosodium glutamate (MSG)-mouse model of obesity. Specific activities, protein and mRNA expressions of these enzymes in liver as well as in small intestine were compared in obese male mice and in their lean counterparts. Furthermore, expression of the NF-E2-related factor 2 (Nrf2) and its relation to obesity was tested. Obtained results showed that obesity affects expression and/or activities of some DME and antioxidant enzymes. In obese mice, up-regulation of UDP-glucuronosyltransferases 1A (UGT1A), NAD(P)H: quinone oxidoreductase 1(NQO1), nuclear transcription factor Nrf2 and down regulation of some isoforms of glutathione S-transferases (GST) were observed. Most of these changes were tissue and/or isoform specific. NQO1 seems to be regulated transcriptionally via Nrf2, but other enzymes might be regulated post-transcriptionally and/or post-translationally. Enhanced expression of Nrf2 in livers of obese mice is expected to play a role in protective adaptation. On the other hand, elevated activities of NQO1 and UGT1A may cause alterations in drug pharmacokinetics in obese individuals. Moreover, decreased capacity of GST in obese animals indicates potentially reduced antioxidant defense and weaker chemoprotection.
- animal models
- glutathione conjugates/glutathione transferases/GST
- liver/hepatic
- NAD(P)H-quinone oxidoreductase
- Nrf2
- The American Society for Pharmacology and Experimental Therapeutics