Synthesis, antimicrobial activity and quantum chemical investigation of novel succinimide derivatives
2019
Authors:
Petković Cvetković, JelenaBožić, Bojan Đ.
Banjac, Nebojša R.
Petrović, Jovana
Soković, Marina
Vitnik, Vesna D.
Vitnik, Željko J.
Ušćumlić, Gordana S.
Valentić, Nataša V.
Document Type:
Article (Published version)
,
© 2018 Elsevier B.V.
Metadata
Show full item recordAbstract:
The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in inflammation, regulation of energy metabolism and glucocorticoid action. Chronic low-grade inflammation may be caused by fructose intake, contributing to visceral adipose tissue (VAT) dysfunction. Since MIF is a known antagonist of glucocorticoid signaling, and deregulated glucocorticoid signaling can contribute to lipid metabolism disturbances, we hypothesized that altered MIF signaling might underlie fructose-induced adiposity through glucocorticoid action. We analyzed physiological and biochemical parameters, adipose tissue histology, insulin sensitivity and lipid metabolism in wild type and MIF-/- C57Bl/6J mice consuming 20% fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and glucocorticoid receptor (GR) protein level were examined in VAT, together with the expression of glucocorticoid-target genes involved in lipid metabolism. The expression of adipogenic and lipogenic transcriptional regulators peroxisome proliferator activated receptor gamma (PPARG) and sterol regulatory element-binding protein 1c (SREBP1c) was also assessed. Results showed disturbed insulin sensitivity in all MIF-/- mice, regardless of the diet. Mice on fructose diet had increased energy intake, but increased visceral adiposity and enlarged adipocytes were observed only in fructose-fed MIF-/- mice. Increased VAT corticosterone level and 11 beta-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase and GR protein levels were observed in the same animals, together with induced expression of examined lipogenic genes and accumulation of PPARG and SREBP1c. In conclusion, the results showed that dietary fructose was associated with increased visceral adiposity through activation of GR-regulated lipogenic genes, but only in the absence of MIF, which set the state of hyperinsulinemia and insulin resistance.
Keywords:
Succinimide; Antimicrobial activity; Antifungal activity; DFT calculation; Structure-activity relationshipSource:
Journal of Molecular Structure, 2019, 1181, 148-156Funding / projects:
- Study of the Synthesis, Structure and Activity of Natural and Synthetic Organic Compounds (RS-MESTD-Basic Research (BR or ON)-172013)
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-MESTD-Basic Research (BR or ON)-172035)
- Bioinformatic promoter predictions and theoretical modeling of gene circuits in bacteria (RS-MESTD-Basic Research (BR or ON)-173052)
- Investigating the possibility of using contaminated waters for cultivation of pseudocereals (RS-MESTD-Technological Development (TD or TR)-31006)
- Characterization and application of fungal metabolites and assessment of new biofungicides potential (RS-MESTD-Basic Research (BR or ON)-173032)
- Modeling and Numerical Simulations of Complex Many-Body Systems (RS-MESTD-Basic Research (BR or ON)-171017)
DOI: 10.1016/j.molstruc.2018.12.083
WoS: 000458612300016
Scopus: 2-s2.0-85059576086
URI
https://www.sciencedirect.com/science/article/pii/S0022286018315163?via%3Dihubhttps://radar.ibiss.bg.ac.rs/handle/123456789/3239