SFEBES2023 Poster Presentations Metabolism, Obesity and Diabetes (70 abstracts)
Female AKR1D1 knockout mice are protected against diet induced obesity and insulin resistance but not hepatic steatosis
Maira Bailey 1 , Tom Potter 1 , Dean Larner 2 , Stuart Morgan 3 , Gareth Lavery 2 , Jeremy Tomlinson 4 & Laura Gathercole 1
1Oxford Brookes University, Oxford, United Kingdom. 2Nottingham Trent University, Nottingham, United Kingdom. 3University of Birmingham, Birmingham, United Kingdom. 4University of Oxford, Oxford, United Kingdom
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 AKR1D1KO mice. Female wildtype and AKR1D1KO mice were challenged with a 60% high-fat diet for 20-weeks. AKR1D1KO mice were protected from diet induced obesity (weight gain: 27.2±0.5 g [WT], 15.8±1.2 g [KO], P<0.01), with reduced adipose tissue mass (gonadal: 4.0±0.2 g [WT], 2.4±0.4 g [KO], P<0.005; subcutaneous: 3.9±0.3 g [WT], 2.4±0.5 g [KO], P<0.05). Female AKR1D1KO mice were also protected against glucose intolerance (ipGTT AUC: 3216 mmol×min [WT], 2601 mmol×min [KO], P<0.05) and insulin resistance (ipITT AUC: 1171 mmol×min [WT], 947 mmol×min [KO], P<0.05). Despite being protected against diet induced obesity, female AKR1D1KO mice had a similar degree of steatosis as the wildtype mice. Suggesting an increase in lipogenesis, the mRNA expression of Acc1 (relative expression: 0.85±0.10 [WT], 0.19±0.11 [KO], P<0.05) was increased. There was no change in the expression of genes involved in b-oxidation (Acc2 and Cpt1), lipid uptake (Lipc) or export (Apoa4). In summary, despite being protected against diet induced obesity female AKR1D1KO mice have a similar degree of steatosis to high fat fed wildtype mice. Gene expression analysis suggests this is, at least partially, driven by an increase in lipogenesis but further studies are needed to confirm the underlying mechanisms.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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