GendAge Weight Loss Study

Obesity increases the risk of diseases such as type 2 diabetes, cardiovascular disease, and several cancers. Increased body fat, particularly abdominal obesity around the vital organs, contributes to these health risks. With nearly two-thirds of the UK population living with overweight or obesity, there is a desperate need to provide evidence-based public health advice for obesity management. Dieting, involving a sustained calorie deficit, can reduce body weight and specifically, the amount of body fat. This reduction in body fat offers many health benefits, including improved blood sugar control, at least while weight loss is maintained. Therefore, current weight management advice is around lifestyle modification, with diet and physical activity changes to support calorie deficit. However, current dieting advice does not account for gender or age. This is a surprising oversight: it is well established that health outcomes differ substantially between men and women, and our recent research in mice and humans has revealed that females resist weight loss and fat loss in response to dieting. In mice, males lose more weight and fat mass than females, but only at younger ages; older females increase their ability to lose fat, responding similarly to males. To determine if this occurs in humans, we reanalysed data from one of our previous studies of dieting in 45 men and women. This revealed that, as in mice, men lose more weight than women, regardless of age. Strikingly, we found that males' increased fat loss occurred only in the younger participants (<45 years), with a greater loss of muscle tissue in the older age group (>45 years). Muscle loss has negative longer-term health effects, so this should be minimised during dieting. In summary our work demonstrates that age-sex differences do not favour dieting for fat loss in younger females. As females age, the sex hormone, oestrogen, decreases, linked to menopause at around the age of 50 years. Thus, one possibility is that oestrogen directly influences these age-sex differences in the dieting response. Understanding how to maximise fat loss and minimise muscle loss during calorie deficit will positively affect health outcomes, particularly the effects on blood sugar control. However, our previous human studies were not designed to explore these age and sex differences or their underlying basis. Such thorough understanding requires highly controlled diet studies in volunteers, within a controlled environment, to fully measure changes in energy intake, energy expenditure and body composition. This is the goal of our planned research. We propose to conduct a diet study in 60 men and women, with all food provided, and monitor changes in energy expenditure and body composition using gold-standard techniques. We will collect blood samples and fat tissue samples, from under the skin in the leg, to examine if mechanisms associated with sex hormones can explain these sex and age differences in calorie restriction. Considering the potential role of oestrogen, women who replace hormones using hormone replacement therapy (HRT) may have a reduced response to calorie deficit because they have a similar hormone profile to younger women. To test this hypothesis, we will recruit a small cohort of older females (n=15), who take HRT, to participate in the same dieting study, to assess the interaction of sex hormones and age. Together, these studies support translational understanding of diet and womens' health to combat obesity and achieve healthy ageing.