@article{
author = "Mićić, Bojana and Đorđević, Ana and Veličković, Nataša and Kovačević, Sanja and Martić, Teodora and Macut, Đuro and Vojnović-Milutinović, Danijela",
year = "2023",
abstract = "Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive
age, often associated with obesity and insulin resistance. Childhood obesity is an important
predisposing factor for the development of PCOS later in life. Being particularly interested in the
interplay between prepubertal obesity and hyperandrogenemia, we investigated the effects of early
postnatal overfeeding, accomplished by reducing litter size during the period of suckling, on energy
sensing and insulin signaling pathways in the gastrocnemius muscle of a rat model of PCOS-induced
by 5 -dihydrotestosterone (DHT). The combination of overfeeding and DHT treatment caused hyperinsulinemia
and decreased systemic insulin sensitivity. Early postnatal overfeeding induced defects
at critical nodes of the insulin signaling pathway in skeletal muscle, which was associated with
reduced glucose uptake in the presence of hyperandrogenemia. In this setting, under a combination
of overfeeding and DHT treatment, skeletal muscle switched to mitochondrial -oxidation of fatty
acids, resulting in oxidative stress and inflammation that stimulated AMP-activated protein kinase
(AMPK) activity and its downstream targets involved in mitochondrial biogenesis and antioxidant
protection. Overall, a combination of overfeeding and hyperandrogenemia resulted in a prooxidative
and insulin-resistant state in skeletal muscle. This was accompanied by the activation of AMPK,
which could represent a potential therapeutic target in insulin-resistant PCOS patients.",
publisher = "Basel: MDPI",
journal = "Biomedicines",
title = "AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding",
number = "6",
volume = "11",
doi = "10.3390/biomedicines11061586",
pages = "1586"
}