Experimental approaches

Physical activity

While it is apparent that physical activity has beneficial effects on health and reduces the negative consequences of excess weight, our understanding of its relationship to obesity - and of its mechanisms, effect size, optimal level and effective implementation for prevention or treatment - is limited. Developments in methodology and the use of cohorts are required to increase progress. Like bariatric surgery, physical activity may be a useful experimental tool with which to examine pathways linking obesity and disease.

  • Mechanistic research - physical activity appears to have a disproportionate effect on health outcomes (particularly insulin resistance and blood pressure) compared to its effect on weight, breaking the link between obesity and disease. As with bariatric surgery, increased understanding of the mechanistic basis of these effects will likely yield significant insights and novel therapeutic targets.
  • Investigation of the determinants and effects of exercise and sedentary behaviour; physiology, genetics and social/environmental factors in regulation of exercise levels and sedentary behaviour.
  • Incorporation of valid and relevant physical activity and sedentary behaviour measurements into large cohorts.
  • Development of effective and efficient interventions to increase physical activity in contemporary populations.

Ethnicity and obesity

Different ethnic groups vary in susceptibility to obesogenic environments and to the adverse consequences of obesity, for both genetic/physiological and cultural/behavioural reasons. Effective interventions may also depend on the social and cultural context in which they are applied. The study of ethnic differences, and of the impacts of migration on specific population groups, may provide important mechanistic insights into pathways to obesity risk and its adverse consequences. Additionally, information on the propensities of different ethnic groups to obesity and its adverse consequences will be valuable for clinical decision-making.

  • Ethnic differences and migration patterns provide useful experimental tools for gene-environment interaction studies and for research into cultural influences on obesity.
  • Research should aim to understand the genetic and environmental factors that cause variations in the prevalence and incidence of metabolic disorders and their antecedents in specific populations.

Bariatric surgery as an experimental model

Bariatric surgery is an effective intervention for obesity and its metabolic consequences but its mechanism of action is poorly understood, particularly why positive metabolic effects are observed before (or independently of) weight loss. This may be a result of the surgery itself, or a consequence of the marked caloric restriction that follows. The clinical use of bariatric surgery provides an excellent opportunity to use it as a model to understand the mechanisms of the adverse physiological effects of obesity. The use of bariatric surgery as an experimental tool will provide important insights into gut-brain interactions, linking priorities in mechanistic and neuroendocrine research. Suggested developments include:

  • Using bariatric surgery as an experimental tool to understand actions of and synergies between appetite regulation hormones, providing a basis for pharmacological simulation of surgery.
  • Application of human and mouse genetics to bariatric surgery (including identification of responders/non-responders). Related studies, such as caloric restriction in the Ob/Ob mouse, have already generated insights.
  • Establishment of an intensively phenotyped, UK-wide bariatric surgery cohort, integrating clinical and basic science.

Global health

Obesity is a global problem, including low-income countries and sub-Saharan Africa, but its causes (aside from at the most fundamental level) and consequences vary across countries and regions. There are special challenges driven by the burden of disease in low-income countries and metabolic diseases represent one category of emerging non-communicable diseases.

  • Importance of ‘global health’ view in obesity research – interventions suitable for developing-world settings need to be developed and tested locally, as context may be important. This provides opportunities for collaborative endeavours between researchers in developed and developing nations.

Method development (including dietary behaviour)

In many areas, obesity research is limited by a need for improved methodology. In particular, accurate, informative but scalable measurement techniques applicable to large studies are required. For example, the assessment of energy expenditure by doubly-labelled water is accurate but too expensive and time-consuming to be applied to large cohorts. Developments in the following areas would be especially useful:

  • Measurement of dietary habits (including food intake and eating behaviour).
  • Measurement of physical activity and sedentary behaviour.
  • Better (statistical) methods for evaluating natural experiments and for designing experiments in natural settings.
  • Models for feeding behaviour.

Given that many of these areas are technically complicated, the best results are likely to come from collaborations between health researchers and researchers in other technical and mathematical sciences such as engineering and statistics.