A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats
Samo za registrovane korisnike
2016
Autori
Stanimirović, JulijanaObradović, Milan M.
Jovanović, Aleksandra
Sudar, Emina
Zafirović, Sonja
Pitt, Samantha J.
Stewart, Alan J.
Isenović, Esma R.
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NF kappa B, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA an...d FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NF kappa B-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. (C) 2016 Elsevier Inc. All rights reserved.
Ključne reči:
High fat diet / Sex differences / Insulin resistance / Liver metabolism / Nitrite/nitrateIzvor:
Nitric Oxide: Biology and Chemistry, 2016, 54, 51-59Izdavač:
- Elsevier
Finansiranje / projekti:
- Hormonska regulacija ekspresije i aktivnosti azot oksid sintaze i natrijum-kalijumove pumpe u eksperimentalnim modelima insulinske rezistencije, dijabetesa i kardiovaskularnih poremećaja (RS-MESTD-Basic Research (BR or ON)-173033)
- Integralna studija identifikacije regionalnih genetskih faktora rizika i faktora rizika životne sredine za masovne nezarazne bolesti humane populacije u Srbiji - INGEMA_S (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41028)
DOI: 10.1016/j.niox.2016.02.007
ISSN: 1089-8603; 1089-8611
PubMed: 26924725
WoS: 000373658000006
Scopus: 2-s2.0-84960354313
Kolekcije
Institucija/grupa
VinčaTY - JOUR AU - Stanimirović, Julijana AU - Obradović, Milan M. AU - Jovanović, Aleksandra AU - Sudar, Emina AU - Zafirović, Sonja AU - Pitt, Samantha J. AU - Stewart, Alan J. AU - Isenović, Esma R. PY - 2016 UR - https://vinar.vin.bg.ac.rs/handle/123456789/1004 AB - Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NF kappa B, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NF kappa B-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. (C) 2016 Elsevier Inc. All rights reserved. PB - Elsevier T2 - Nitric Oxide: Biology and Chemistry T1 - A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats VL - 54 SP - 51 EP - 59 DO - 10.1016/j.niox.2016.02.007 ER -
@article{ author = "Stanimirović, Julijana and Obradović, Milan M. and Jovanović, Aleksandra and Sudar, Emina and Zafirović, Sonja and Pitt, Samantha J. and Stewart, Alan J. and Isenović, Esma R.", year = "2016", abstract = "Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NF kappa B, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NF kappa B-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. (C) 2016 Elsevier Inc. All rights reserved.", publisher = "Elsevier", journal = "Nitric Oxide: Biology and Chemistry", title = "A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats", volume = "54", pages = "51-59", doi = "10.1016/j.niox.2016.02.007" }
Stanimirović, J., Obradović, M. M., Jovanović, A., Sudar, E., Zafirović, S., Pitt, S. J., Stewart, A. J.,& Isenović, E. R.. (2016). A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats. in Nitric Oxide: Biology and Chemistry Elsevier., 54, 51-59. https://doi.org/10.1016/j.niox.2016.02.007
Stanimirović J, Obradović MM, Jovanović A, Sudar E, Zafirović S, Pitt SJ, Stewart AJ, Isenović ER. A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats. in Nitric Oxide: Biology and Chemistry. 2016;54:51-59. doi:10.1016/j.niox.2016.02.007 .
Stanimirović, Julijana, Obradović, Milan M., Jovanović, Aleksandra, Sudar, Emina, Zafirović, Sonja, Pitt, Samantha J., Stewart, Alan J., Isenović, Esma R., "A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats" in Nitric Oxide: Biology and Chemistry, 54 (2016):51-59, https://doi.org/10.1016/j.niox.2016.02.007 . .