title: Central leptin resistance and hypothalamic inflammation are involved in letrozole-induced polycystic ovary syndrome rats.
abstract: Accumulating evidence indicates that leptin acts as an important mediator in energy homeostasis and reproduction. Since dysfunction of reproduction and metabolism are major characteristics of polycystic ovarian syndrome (PCOS), the role of leptin in pathogenesis of PCOS needs further research. Many studies have shown that central leptin resistance existed in obesity rats through leptin intracerebroventricular (icv) injection; however, central leptin resistance in PCOS rats has not been reported. This study aimed to investigate whether there was a state of central leptin resistance in PCOS rats, as well as explore the possible association of hypothalamic inflammation with central leptin resistance. First, letrozole was used to induce the PCOS model, 24 h food intake, 24 h body weight changes and the expression of p-STAT3 were determined following leptin or artificial cerebrospinal fluid (aCSF) icv injection in rats. Second, we further evaluated the expressions of IL-1β, IL-6, TNF-α, p-IKKβ, NF-κB, p-NF-κB, IκBα, p-IκBα and SOCS3 in hypothalamus. The results showed that 24 h food intake and body weight were decreased, while the expression of p-STAT3 was increased in control group rats following leptin icv injection compared with aCSF icv injection; however, both of them showed no significant difference in PCOS rats. Furthermore, inflammatory markers were upregulated in the hypothalami of PCOS rats. Taken together, our data indicated that there was a state of chronic low-grade inflammation in hypothalamus which might be the possible mechanism for central leptin resistance in PCOS rats.
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, PR China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, PR China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Lian
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, PR China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, PR China.
authors.forename: Fangui
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, PR China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, PR China. Electronic address: wjwwang@aliyun.com.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001835:Body Weight; D004435:Eating; D005260:Female; D007031:Hypothalamus / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D020738:Leptin / Q000276:immunology*; D000077289:Letrozole; D009570:Nitriles; D010053:Ovary / Q000276:immunology / Q000473:pathology*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000276:immunology; D014230:Triazoles
chemical_list: D020738:Leptin; D009570:Nitriles; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D014230:Triazoles; D000077289:Letrozole
keywords: Central leptin resistance; Inflammation; Polycystic ovary syndrome