Overview

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.

Eligibility

Inclusion criteria

• Adults (aged over 18years) who are healthy but overweight/obese (BMI 27-45kg/m2) males and females as:
• 15 women (age 40 or less years)
• 15 men (age 40 or less years)
• 15 women (age 55-65 years) in menopause*; not taking Hormone Replacement Therapy (HRT)
• 15 men (age 55-65 years)
• 15 women (age 55-65 years) in menopause; taking HRT**
  • menopause definition is no menstrual period for 12 months **HRT inclusion criteria - women will have continuously taken oestrogen HRT for 24 months

Exclusion criteria:

Potential volunteers will be asked to fill in a health questionnaire at the screening visit to assess their suitability for the study. This information will allow us to exclude participants.

Medication exclusion criteria, current use :-

• weight loss medication (e.g. GLP agonists), β-blockers, antihistamines, antipsychotics, benzodiazepines, barbiturates, melatonin, Ritalin, modafinil, soporifics, hypnotics, antiepileptic drugs, diabetes medication (e.g. metformin or insulin).

Self-reported medical exclusion criteria:

• Females who are planning to be pregnant, are pregnant or are breastfeeding
• Anyone with coeliac disease or gluten intolerance or food allergy
• Anyone with diagnosed T1 or T2 diabetes
• Anyone suffering from a psychiatric disorder or any type of substance abuse

Other exclusion criteria

• Anyone following a vegetarian or vegan diet
• Anyone currently following a weight loss programme (that may be affecting lifestyle, physical activity & diet) or undergone gastric band/reduction surgery; including GLP agonist (e.g. Semaglutide injection, Ozempic®).
• Anyone currently participating in another research study
• Anyone with unsuitable veins for blood sampling
• Anyone who is unable to fluently speak, read and understand English
• Anyone who is unable to comply to an alcohol-free diet for 6 weeks
• Anyone unable to give fully informed consent