Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

ABRUZZESE, G.A.; HEBER, M.F.; FERREIRA, S.R.; VELEZ, L.M.; REYNOSO, R.B.; PIGNATARO, O.P.; MOTTA, A.B.

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2016

0022-0795

Prenatal hyperandrogenism is hypothesized as one of the main factors contributingto the development of polycystic ovary syndrome (PCOS). PCOS patients have highrisk of developing fatty liver and steatosis. This study aimed to evaluate the role ofprenatal hyperandrogenism in liver lipid metabolism and fatty liver development.Pregnant rats were hyperandrogenized with testosterone. At pubertal age, theprenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov)and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluatedhepatic transferases, liver lipid content, the balance between lipogenesis and fatty acidoxidation pathway, oxidant/antioxidant balance and proinflammatory status. We alsoevaluated the general metabolic status through growth rate curve, basal glucose andinsulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Althoughneither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidationpathways were altered. The PH groups also showed impaired oxidant/antioxidantbalance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 andcyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipidsand increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenismgenerates both PHov and PHanov phenotypes with signs of liver alterations, imbalancein lipid metabolism and increased risk of developing metabolic syndrome. Theanovulatory phenotype showed more alterations in liver lipogenesis and a moreimpaired balance of insulin and glucose metabolism, being more susceptible to thedevelopment of steatosis.