TY  - JOUR
AU  - Veličković, Nataša
AU  - Mićić, Bojana
AU  - Teofilović, Ana
AU  - Milovanović, Milena
AU  - Jovanović, Mirna
AU  - Đorđević, Ana
AU  - Macut, Djuro
AU  - Vojnović Milutinović, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/7009
AB  - Background: Polycystic ovary syndrome (PCOS) is the most common endocrine
disorder in women of reproductive age and is closely associated with chronic
low-grade inflammation and insulin resistance. To clarify the contribution of
prepubertal weight gain to the development of insulin resistance in PCOS, we
investigated the effects of early postnatal overfeeding on inflammatory and
energy-sensing pathways as well as on markers of insulin signaling in the liver
of the PCOS rat model.
Methods: Obesity induced by overfeeding was achieved by reducing litter size,
while the PCOS-like condition was developed by treatment with 5a-
dihydrotestosterone (DHT). Western blot and qPCR were used to analyze the
expression of pro-inflammatory transcription factors and cytokines, as well as
markers of the energy sensing and insulin signaling pathways.
Results: The results showed that hepatic insulin sensitivity was impaired only in
DHT-treated rats raised in small litters, as evidenced by increased
phosphorylation of IRS1 on Ser307 and decreased expression of total IRS1.
Postnatal overfeeding stimulated JNK1 activation independent of
hyperandrogenemia; nevertheless, the synergistic effect of both factors
triggered NLRP3 activation and increased IL1b expression in the small litter
DHT-treated group. This pro-inflammatory state was accompanied by
decreased activatory phosphorylation of AMPK and reduced levels of its
protein targets.
Conclusions: Overfeeding in the early postnatal period leads to a decrease in
hepatic insulin sensitivity in the rat model of PCOS, which is associated with
decreased activation of AMPK and stimulation of the hepatic NLRP3-IL1b
signaling pathway. Accordingly, the inhibition of NLRP3 activation could
provide a basis for the development of new therapeutic strategies for the
treatment of insulin resistance in women with PCOS.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Endocrinology
T1  - Overfeeding in the early postnatal period aggravates inflammation and hepatic insulin sensitivity in the 5a-dihydrotestosterone-induced animal model of PCOS
VL  - 15
DO  - 10.3389/fendo.2024.1402905
SP  - 1402905
ER  - 

@article{
author = "Veličković, Nataša and Mićić, Bojana and Teofilović, Ana and Milovanović, Milena and Jovanović, Mirna and Đorđević, Ana and Macut, Djuro and Vojnović Milutinović, Danijela",
year = "2024",
abstract = "Background: Polycystic ovary syndrome (PCOS) is the most common endocrine
disorder in women of reproductive age and is closely associated with chronic
low-grade inflammation and insulin resistance. To clarify the contribution of
prepubertal weight gain to the development of insulin resistance in PCOS, we
investigated the effects of early postnatal overfeeding on inflammatory and
energy-sensing pathways as well as on markers of insulin signaling in the liver
of the PCOS rat model.
Methods: Obesity induced by overfeeding was achieved by reducing litter size,
while the PCOS-like condition was developed by treatment with 5a-
dihydrotestosterone (DHT). Western blot and qPCR were used to analyze the
expression of pro-inflammatory transcription factors and cytokines, as well as
markers of the energy sensing and insulin signaling pathways.
Results: The results showed that hepatic insulin sensitivity was impaired only in
DHT-treated rats raised in small litters, as evidenced by increased
phosphorylation of IRS1 on Ser307 and decreased expression of total IRS1.
Postnatal overfeeding stimulated JNK1 activation independent of
hyperandrogenemia; nevertheless, the synergistic effect of both factors
triggered NLRP3 activation and increased IL1b expression in the small litter
DHT-treated group. This pro-inflammatory state was accompanied by
decreased activatory phosphorylation of AMPK and reduced levels of its
protein targets.
Conclusions: Overfeeding in the early postnatal period leads to a decrease in
hepatic insulin sensitivity in the rat model of PCOS, which is associated with
decreased activation of AMPK and stimulation of the hepatic NLRP3-IL1b
signaling pathway. Accordingly, the inhibition of NLRP3 activation could
provide a basis for the development of new therapeutic strategies for the
treatment of insulin resistance in women with PCOS.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Endocrinology",
title = "Overfeeding in the early postnatal period aggravates inflammation and hepatic insulin sensitivity in the 5a-dihydrotestosterone-induced animal model of PCOS",
volume = "15",
doi = "10.3389/fendo.2024.1402905",
pages = "1402905"
}

Veličković, N., Mićić, B., Teofilović, A., Milovanović, M., Jovanović, M., Đorđević, A., Macut, D.,& Vojnović Milutinović, D.. (2024). Overfeeding in the early postnatal period aggravates inflammation and hepatic insulin sensitivity in the 5a-dihydrotestosterone-induced animal model of PCOS. in Frontiers in Endocrinology
Lausanne: Frontiers Media SA., 15, 1402905.
https://doi.org/10.3389/fendo.2024.1402905

Veličković N, Mićić B, Teofilović A, Milovanović M, Jovanović M, Đorđević A, Macut D, Vojnović Milutinović D. Overfeeding in the early postnatal period aggravates inflammation and hepatic insulin sensitivity in the 5a-dihydrotestosterone-induced animal model of PCOS. in Frontiers in Endocrinology. 2024;15:1402905.
doi:10.3389/fendo.2024.1402905 .

Veličković, Nataša, Mićić, Bojana, Teofilović, Ana, Milovanović, Milena, Jovanović, Mirna, Đorđević, Ana, Macut, Djuro, Vojnović Milutinović, Danijela, "Overfeeding in the early postnatal period aggravates inflammation and hepatic insulin sensitivity in the 5a-dihydrotestosterone-induced animal model of PCOS" in Frontiers in Endocrinology, 15 (2024):1402905,
https://doi.org/10.3389/fendo.2024.1402905 . .