Affiliation:
1. Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland.
2. Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
Abstract
Obesity, which leads to metabolic dysregulation and body function impairment, emerges as one of the pressing health challenges worldwide. Excessive body fat deposits comprise a dynamic and biologically active organ possessing its own endocrine function. One of the mechanisms underlying the pathophysiology of obesity is low-grade systemic inflammation mediated by pro-inflammatory factors such as free fatty acids, lipopolysaccharides, adipokines (including leptin, resistin and visfatin) and cytokines (TNF-α, IL-1β, Il-6), which are secreted by adipose tissue. Together with obesity-induced insulin resistance and hyperandrogenism, the exacerbated immune response has a negative impact on the hypothalamic–pituitary–gonadal axis at all levels and directly affects reproduction. In women, it results in disrupted ovarian function, irregular menstrual cycles and anovulation, contributing to infertility. This review focuses on the abnormal intracellular communication, altered gene expression and signaling pathways activated in obesity, underscoring its multifactorial character and consequences at a molecular level. Extensive presentation of the complex interplay between adipokines, cytokines, immune cells and neurons may serve as a foundation for future studies in search of potential sites for more targeted treatment of reproductive disorders related to obesity.
Reference198 articles.
1. WHO European Regional (2022). Obesity Report 2022, WHO Regional Office for Europe.
2. The Lancet Gastroenterol Hepatol (2021). Obesity: Another ongoing pandemic. Lancet Gastroenterol. Hepatol., 6, 411.
3. Reyes-Farias, M., Fos-Domenech, J., Serra, D., Herrero, L., and Sánchez-Infantes, D. (2021). White adipose tissue dysfunction in obesity and aging. Biochem. Pharmacol., 192.
4. Mitochondrial regulation and white adipose tissue homeostasis;Zhu;Trends Cell Biol.,2022
5. Venkatesh, S.S., Ferreira, T., Benonisdottir, S., Rahmioglu, N., Becker, C.M., Granne, I., Zondervan, K.T., Holmes, M.V., Lindgren, C.M., and Wittemans, L.B.L. (2022). Obesity and risk of female reproductive conditions: A Mendelian randomisation study. PLoS Med., 19.