02 November 2015

Enzyme potential target for fight against obesity and diabetes

Removing an enzyme that controls bile acid and hormone levels significantly protects female mice from weight gain, according to a new study presented today at the Society for Endocrinology annual conference in Edinburgh. The finding offers a new a therapeutic target in the fight against obesity.
Steroid hormones and bile acids have multiple functions that affect appetite, physical activity and how energy is used and stored in the body. For example, the sex hormone oestrogen (a steroid) has previously shown to decrease women’s appetite while firing up their metabolism and levels of physical activity. Bile acids are important to digest fats in diets, without which animals could not make the most out of a fatty food’s calorific content.

The enzyme 5β-Reductase helps generate bile acid and clears excess levels of steroid hormones in the human body.

In this study, researchers from the University of Oxford compared the effects of feeding wild mice a high calorie, fat-rich diet with mice that lacked the ability to make 5β-Reductase over a period of 30 weeks.

Female mice without 5β-Reductase gained 42% less weight than the wild mice (15.8g vs 27.2g respectively), while males in both experimental groups gained the same amount of weight. Female mice without 5β-Reductase also stored less fat around the gonads, vital organs and under their skin compared to wild mice, while also being more sensitive to insulin and better at controlling their blood glucose levels.

“The gender-specific health outcomes of our experiment are interesting but poorly understood”, said lead author of the study Dr Laura Gathercole. “It could be that lacking this key enzyme means female mice are less able to extract energy from their food, spend more energy to power their metabolism, or both at the same time”.

“Tweaking steroid and bile acid levels has significant health implications and so 5β-Reductase could be an important potential therapeutic target in metabolic disease”, she continued.

The researchers next steps are to pinpoint the mechanisms behind the phenomenon, which could provide insights into the different ways males and females regulate their energy and metabolisms.

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