Long-term androgen excess induces insulin resistance and non-alcoholic fatty liver disease in PCOS-like rats.

• Women with polycystic ovary syndrome (PCOS) are at higher risk for metabolic disorders compared to healthy women, and about 51 % of women with PCOS suffer from non-alcoholic fatty liver disease (NAFLD). Investigation into the pathological mechanism behind this association will provide insights for the prevention and treatment of this complication.Dihydrotestosterone (DHT), a nonaromatic androgen, was used to mimic the pathological conditions of hyperandrogenism and insulin resistance. Hematoxylin and eosin staining, Oil Red O staining, immunofluorescent staining, Western blots, and qRT-PCR were used to verify the hepatic steatosis and inflammation, and the latter two methods were also used for energy and mitochondrion-related assays. ELISA was used to measure the level of reactive oxygen species.Twelve weeks of DHT exposure led to obesity and insulin resistance as well as hepatic steatosis, lipid deposition, and different degrees of inflammation. The expression of molecules involved in respiratory chain and aerobic respiration processes, such as electron transfer complex II, pyruvate dehydrogenase, and succinate dehydrogenase complex subunit A, was inhibited. In addition, molecules associated with apoptosis and autophagy were also abnormally expressed, such as increased Bak mRNA, an increased activated caspase-3 to caspase-3 ratio, and increased Atg12 protein expression. All of these changes are associated with the mitochondria and lead to lipid deposition and inflammation in the liver.Long-term androgen excess contributes to insulin resistance and hepatic steatosis by affecting mitochondrial function and causing an imbalance in apoptosis and autophagy, thus suggesting the pathogenesis of NAFLD in women with PCOS.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

Apoptosis

Autophagy

Insulin resistance

Mitochondria

Non-alcoholic fatty liver disease

Polycystic ovary syndrome

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