Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.

Menopause, the permanent cessation of the menstrual cycle, marks the end of a woman's reproductive lifespan. In addition to changes in sex hormone levels associated with menopause, its timing is another predictor of future health outcomes such as duration of the presence of vasomotor symptoms (VMS) and the risk of hormone-related cancers. With ageing of the population, it is estimated that worldwide 1·2 billion women will be menopausal by the year 2030. Previously the effects of reproductive factors (e.g. parity, age at menarche, pregnancy) and socio-demographic factors on intermediate and long-term health outcomes of menopause have been widely documented. However, little is known about whether diet could have an impact on these. Therefore, we review current evidence on the associations of diet with menopause, presence of VMS and the risk of hormone-related cancers such as ovarian, endometrial and breast cancer. Dietary factors could influence the lifespan of the ovaries and sex-hormones levels, hence the timing of natural menopause. Few studies reported an association between diet, in particular soya consumption, and a reduced risk of VMS. Sustained oestrogen exposure has been associated with a higher risk of hormone-related cancers and thus high-fat and meat diets have been linked with an increased risk of these cancers. However, to better understand the mechanistic pathways involved and to make stronger conclusions for these relationships, further studies investigating the associations of dietary intakes and dietary patterns with menopause, presence of VMS and the risk of hormone-related cancers are required.

Physiological and behavioural systems are tolerant of excess energy intake and responsive to energy deficits. Weight loss (WL) changes body structure, physiological function and energy balance (EB) behaviours, which resist further WL and promote subsequent weight regain. Measuring and understanding the response of EB systems to energy deficits is important for developing evidence-based behaviour change interventions for longer-term weight management. Currently, behaviour change approaches for longer-term WL show modest effect sizes. Self-regulation of EB behaviours (e.g. goal setting, action plans, self-monitoring, relapse prevention plans) and aspects of motivation are important for WL maintenance. Stress management, emotion regulation and food hedonics may also be important for relapse prevention, but the evidence is less concrete. Although much is known about the effects of WL on physiological and psychological function, little is known about the way these dynamic changes affect human EB behaviours. Key areas of future importance include (i) improved methods for detailed tracking of energy expenditure, balance and by subtraction intake, using digital technologies, (ii) how WL impacts body structure, function and subsequent EB behaviours, (iii) how behaviour change approaches can overcome physiological resistance to WL and (iv) who is likely to maintain WL or relapse. Modelling physiological and psychological moderators and mediators of EB-related behaviours is central to understanding and improving longer-term weight and health outcomes in the general population.