Endocrine Abstracts

Mitochondria-endoplasmic reticulum contact sites (MERCS) play a key role in cholesterol metabolism and steroidogenesis by facilitating the efficient transfer and processing of cholesterol for steroid hormone synthesis. However, whether MERCS play a role in bile acid synthesis is completely unexplored. Here we begin to investigate a role for MERCS in bile acid synthesis using two alternative models of MERCS disruption. First, to reduce the total number of MERCS we performed siR...

Bile acids and steroid hormones are potent regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in the liver where it catalyses a fundamental step in bile acid synthesis and inactivates steroid hormones. We have previously shown that male, but not female, AKR1D1 knockout (KO) mice on a normal chow diet are leaner than wildtype littermates but are not protected against diet induced obesity. Here we investigate the impact of a high fat diet on female...

Bile acid (BA) homeostasis is disrupted in MASLD with characteristic changes in BA pool composition. BAs are signalling molecules that modulate hepatic lipid metabolism, inflammation, and cellular proliferation via the activation of nuclear receptors, notably FXR. Altered FXR activation has profound effects on the transcription of genes involved in hepatoprotection. We have previously shown that the hepatic enzyme 5β-reductase (AKR1D1), which catalyses a key step...