Sex Hormones as Regulators of the Age- and Sex-dependent Benefits of Caloric Restriction

Obesity increases the risk of type 2 diabetes, cardiovascular disease, and certain cancers, primarily due to elevated abdominal fat storage. With nearly two-thirds of the UK population living with overweight or obesity, there is an urgent necessity for evidence-based public health guidance to promote healthy weight. Calorie deficit can facilitate weight loss and body fat reduction, leading to health benefits, such as improved blood glucose control. Current weight management advice centres on lifestyle modification, incorporating changes to diet and physical activity to support a calorie deficit. However, existing dieting recommendations fail to consider gender or age. This is a surprising oversight, as it is well established that health outcomes vary significantly between men and women across the lifespan. Further, the menopause may have an impact on fat storage linked to changes in sex hormones. Our recent research, involving both mice and humans, has indicated that females are less responsive to weight loss and fat reduction during dieting. This study aims to understand endocrine and metabolic sex-based differences in obesity and calorie restriction, with a particular focus on women's health. We plan to conduct a diet study with 75 participants, encompassing both younger and older men and women, to monitor changes in energy expenditure and body composition using gold-standard techniques, such as doubly-labelled water. Blood and abdominal fat tissue samples will be collected to investigate how sex hormones might elucidate these differences. The aim of the study is to enhance our understanding of diet and women's health to combat obesity and promote healthy ageing.