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Updated: Sep 29, 2025
Assessment of Sexual Behavior of Male Mice
Published on: March 5, 2020
AKR1D1 knockout mice develop a sex-dependent metabolic phenotype.
Laura L Gathercole1,2, Nikolaos Nikolaou1, Shelley E Harris1
1Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK.
Steroid 5β-reductase (AKR1D1) impacts bile acid metabolism. AKR1D1 deficiency in mice shows sex-specific effects on insulin tolerance and lipid profiles, influencing metabolic health.
Area of Science:
- Metabolic Regulation
- Endocrinology
- Biochemistry
Background:
- Steroid 5β-reductase (AKR1D1) is crucial for bile acid synthesis and glucocorticoid metabolism.
- The in vivo role of AKR1D1 in controlling metabolic phenotypes remains unclear.
Purpose of the Study:
- To investigate the in vivo metabolic effects of AKR1D1 deficiency.
- To determine the impact of AKR1D1 on bile acid and glucocorticoid homeostasis.
- To assess sex-specific metabolic phenotypes in Akr1d1-/- mice.
Main Methods:
- Generation of Akr1d1-/- mice on a C57BL/6 background.
- Utilized liquid chromatography/mass spectrometry, metabolomics, and transcriptomics.
- Evaluated metabolic phenotypes (body weight, composition, glucose/insulin tolerance, lipid homeostasis) and molecular changes (RNA-Seq, Western blotting).
Main Results:
- Akr1d1-/- mice exhibited sex-specific metabolic phenotypes.
- Male Akr1d1-/- mice showed improved insulin tolerance and reduced hepatic/adipose lipid accumulation but had hypertriglyceridemia.
- Phenotype linked to sex-specific bile acid alterations, with no major changes in glucocorticoid levels or liver gene expression.
Conclusions:
- AKR1D1 is essential for maintaining bile acid homeostasis in vivo.
- Altering AKR1D1 activity influences insulin tolerance and lipid metabolism in a sex-dependent manner.
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