Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine

Autor: Martina Sabatini, Michael Rogowski, Grazia Chiellini, Riccardo Zucchi, Ebru S. Selen Alpergin, Fariba M. Assadi-Porter, Zeinab Bolandnazar
Rok vydání: 2016
Předmět:
0301 basic medicine
medicine.medical_specialty
steroidogenesis
Magnetic Resonance Spectroscopy
endocrine
Physiology
3‐iodothyronamine (T1AM)
Gene Expression
030209 endocrinology & metabolism
Biology
03 medical and health sciences
Mice
0302 clinical medicine
3-iodothyronamine (T1AM)
lipid metabolism
metabolomics
Nuclear magnetic resonance (NMR) spectroscopy
polycystic ovary syndrome (PCOS)
Physiology (medical)
Internal medicine
medicine
Thyronines
Animals
Metabolomics
Carnitine
Obesity
Triglycerides
Original Research
Polycystic ovary syndrome (PCOS)
Muscles
Fatty liver
Ovary
Lipid metabolism
medicine.disease
Polycystic ovary
3. Good health
Metabolic pathway
Oxidative Stress
030104 developmental biology
Endocrinology
Cholesterol
Liver
CYP17A1
Quality of Life
Female
Metabolic Networks and Pathways
Hormone
medicine.drug
Polycystic Ovary Syndrome
Zdroj: Physiological Reports
ISSN: 2051-817X
Popis: 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 (T1AM), a natural analog of thyroid hormone, in a mouse model of PCOS and analyzed plasma and tissue extracts using multidisciplinary omics and biochemical approaches. T1AM administration induces a profound tissue‐specific antilipogenic effect in liver and muscle by lowering gene expression of key regulators of lipid metabolism, PTP1B and PLIN2, significantly increasing metabolites (glucogenic, amino acids, carnitine, and citrate) levels, while enhancing protection against oxidative stress. In contrast, T1AM has an opposing effect on the regulation of estrogenic pathways in the ovary by upregulating STAR , CYP11A1, and CYP17A1. Biochemical measurements provide further evidence of significant reduction in liver cholesterol and triglycerides in post‐T1AM 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.
Databáze: OpenAIRE
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