Dysregulation of Δ⁴-3-oxosteroid 5β-reductase in diabetic patients: Implications and mechanisms.

ABSTRACT: Aldo-keto reductase family 1 member D1 (AKR1D1) is a Δ⁴-3-oxosteroid 5β-reductase required for bile acid synthesis and steroid hormone metabolism. Both bile acids and steroid hormones, especially glucocorticoids, play important roles in regulating body metabolism and energy expenditure. Currently, our understanding on AKR1D1 regulation and its roles in metabolic diseases is limited. We found that AKR1D1 expression was markedly repressed in diabetic patients. Consistent with repressed AKR1D1 expression, hepatic bile acids were significantly reduced in diabetic patients. Mechanistic studies showed that activation of peroxisome proliferator-activated receptor-α (PPARα) transcriptionally down-regulated AKR1D1 expression in vitro in HepG2 cells and in vivo in mice. Consistently, PPAR

SUBMITTER: Valanejad L 

PROVIDER: S-EPMC5891389 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature