Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women

Irene Pradas,Victor M Victor,Mariona Jové,Alba Naudí,Susana Rovira-Llopis,Milagros Rocha,Antonio Hernandez-Mijares,Reinald Pamplona,Celia Bañuls

doi:10.1038/s41598-019-52263-w

Abstract

Metformin is one of the treatments used for PCOS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Unfortunately, there is little known about metformin’s effects on lipid metabolism, a crucial process in PCOS pathology. We have employed a lipidomic approach to explore alterations in the plasma lipid profile of patients with PCOS following metformin treatment. The aim is to offer new insights about the effect of metformin in PCOS patients. Plasma samples were obtained from 27 subjects prior to and following 12 weeks of metformin treatment. A detailed biochemical characterization and lipidomic profile was performed. Metformin reduces BMI, HOMA-IR, FSH and androstenedione and increases DHEA-S but no changes were found in glucose levels after treatment. Multivariate statistics revealed a specific lipidomic signature due to the effect of 12 weeks of metformin treatment in PCOS patients. This signature includes changes in sphingolipid metabolism suggesting a crosstalk between these lipid species and the androgenic metabolism and a decrease in oxidized lipids reinforcing that metformin treatment improves oxidative stress status. Our study confirms the specific effect of metformin in lipid metabolism on women with PCOS after 12 weeks of treatment.

Highlights

Metformin is one of the treatments used for Polycystic ovary syndrome (PCOS) pathology decreasing body weight, plasma androgen, FSH and glucose levels
Parameters related to lipid metabolism were similar in PCOS patients after metformin treatment
When we evaluated other parameters based on fatty acid composition, such as saturated fatty acids (SFA), unsaturated fatty acids (UFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), PUFAn-3, PUFAn-6, double bond index (DBI), peroxidizability index (PI), and anti-inflammatory index (AI), no differences were found in PCOS patients after the metformin treatment

Summary

Introduction

Metformin is one of the treatments used for PCOS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Our study confirms the specific effect of metformin in lipid metabolism on women with PCOS after 12 weeks of treatment. Polycystic ovary syndrome (PCOS) is a multifactorial disorder that affects 7–9% of women of a reproductive age, and is characterized by clinical/biochemical hyperandrogenism, polycystic ovarian morphology (during ultrasound) and chronic oligo-anovulation It is a multifaceted disease in which uncontrolled ovarian steroidogenesis, excessive oxidative stress, aberrant insulin signaling, and genetic/environmental factors play a role[1]. A recent study performed with PCOS patients without associated pathologies and presenting a non-pathogenic lipid profile (Total cholesterol, LDL-C, HDL-C and TG) describes the presence of a PCOS lipidomic fingerprint, in which glycerolipid, glycerophospholipid and sphingolipid metabolism is affected[21], suggesting that these molecules are related to the physiopathology of PCOS and opening up new scenarios in the search for new drugs. Further lipidomic studies that analyse 325 lipid species in women with or without PCOS show an association of BMI with 12 classes of lipid species including phospholipids, ceramides, gangliosides and acylglycerols, and a free androgen index with 8 classes of lipids, namely ceramides, phospholipids and acylglycerols, supporting prior findings that adiposity is a key driver of dyslipidaemia in PCOS24

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