Obesity is the current major cause of premature death in the UK, killing almost 1000 people a week. Worldwide its prevalence is accelerating. The administration of the naturally occurring gut hormone may offer a long-term therapeutic approach to weight control.

Currently, the department is divided into several research groupings:

• Regulatory peptides and hypothalamic group
• Cell transformation group
• Thyroid hormone, bone development and heparan sulphate proteoglycans group
• Forensic toxicology group

Regulatory Peptides and Hypothalamic Group

This is the largest group, led by Steve Bloom, with approximately 50 members, consisting of both clinicians and basic scientists at all levels of their training.

The department has a high publication rate in prestigious international journals and these articles are very highly cited. Between 1980 to 1989 the laboratory was the most highly cited in Europe.

The group's recent work on the administration of the gastrointestinal hormones oxyntomodulin and PYY to human subjects as potential obesity therapies has recently received much media attention. Many peptides are synthesised and released from the gastrointestinal tract. Whilst their roles in regulation of gastrointestinal function have been known for some time,it is now evident that they also influence eating behaviour. Peptide YY (PYY) is released post prandially from the gastrointestinal L-cells with glucagon-like peptide 1 (GLP-1) and oxyntomodulin.

Peptide YY

Recent work from the department has shown that following peripheral administration of PYY 3-36, the circulating form of PYY, to mouse, rat or human there is marked inhibition of food intake1. Obese subjects have lower basal fasting PYY levels and have a smaller post prandial rise. However, obesity does not appear to be associated with resistance to PYY (as it is with leptin) and exogenous infusion of PYY 3-36 results in a reduction in food intake by 30% in an obese group and 31% in a lean group2.

Suggesting that replacing PYY in obese people may prove a promising and novel therapeutic anti obesity treatment.

Oxyntomodulin

Like GLP-1, OXM is also secreted by L cells of the small intestine in response to a meal. In both rodents3 and in man4 OXM inhibits energy intake. A recent study investigated the effect of subcutaneously administered oxyntomodulin on body weight in healthy overweight and obese volunteers. Participants self-administered saline or oxyntomodulin subcutaneously in a randomized, double-blind, parallel-group protocol. Injections were self-administered for 4 weeks, three times daily, 30 min before each meal. The volunteers were asked to maintain their regular diet and level of physical exercise during the study period. Subjects' body weight, energy intake, and levels of adipose hormones were assessed at the start and end of the study. Body weight was reduced by 2.3 +/- 0.4 kg in the treatment group over the study period compared with 0.5 +/- 0.5 kg in the control group. On average, the treatment group had an additional 0.45-kg weight loss per week5. Oxyntomodulin treatment resulted in weight loss and a change in the levels of adipose hormones consistent with a loss of adipose tissue. The anorectic effect was maintained over the 4-week period. Oxyntomodulin represents a potential therapy for obesity.