Open AccessMetabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3‐iodothyronamine
Author(s) -
Selen Alpergin Ebru S.,
Bolandnazar Zeinab,
Sabatini Martina,
Rogowski Michael,
Chiellini Grazia,
Zucchi Riccardo,
AssadiPorter Fariba M.
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13097
Subject(s) - polycystic ovary , cyp17a1 , biology , hormone , endocrinology , metabolic syndrome , lipid metabolism , medicine , insulin resistance , obesity , biochemistry , enzyme
Complex diseases such as polycystic ovary syndrome ( PCOS ) are associated with intricate pathophysiological, hormonal, and metabolic feedbacks that make their early diagnosis challenging, thus increasing the prevalence risks for obesity, cardiovascular, and fatty liver diseases. To explore the crosstalk between endocrine and lipid metabolic pathways, we administered 3‐iodothyronamine (T1 AM ), a natural analog of thyroid hormone, in a mouse model of PCOS and analyzed plasma and tissue extracts using multidisciplinary omics and biochemical approaches. T1 AM administration induces a profound tissue‐specific antilipogenic effect in liver and muscle by lowering gene expression of key regulators of lipid metabolism, PTP 1B and PLIN 2, significantly increasing metabolites (glucogenic, amino acids, carnitine, and citrate) levels, while enhancing protection against oxidative stress. In contrast, T1 AM has an opposing effect on the regulation of estrogenic pathways in the ovary by upregulating STAR , CYP 11A1, and CYP 17A1. Biochemical measurements provide further evidence of significant reduction in liver cholesterol and triglycerides in post‐T1 AM treatment. Our results shed light onto tissue‐specific metabolic vs. hormonal pathway interactions, thus illuminating the intricacies within the pathophysiology of PCOS . This study opens up new avenues to design drugs for targeted therapeutics to improve quality of life in complex metabolic diseases.