PYY3-36 as an anti-obesity drug target.

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

A randomised controlled trial evaluating the use of enteral nutritional supplements postoperatively in malnourished surgical patients.

BACKGROUND: Patients who undergo surgery are at risk of malnutrition due to periods of starvation, the stress of surgery, and subsequent increase in metabolic rate. There are limited data on nutritional outcome of surgical patients. AIMS: To investigate changes in nutritional status and the influence of oral supplements on nutritional status, morbidity, and quality of life in postoperative surgical patients. METHODS: Entry was determined by the presence of malnutrition, as defined by a body mass index (BMI) < or =20 kg/m(2), anthropometric measurements < or =15th percentile on admission, or initiation of oral diet postoperatively and/or a weight loss of 5% or more during the operative period. We studied 101 patients: 52 were randomised to the treatment group (TG) and prescribed a 1.5 kcal/ml nutritional supplement; 49 patients were randomised to the control group (CG) and continued with routine nutritional management. Nutritional status was assessed by weight, anthropometry, and grip strength, with measurements taken at two weekly intervals for 10 weeks. Complications, namely wound infection, chest infection, and antibiotic use were documented. Quality of life (QOL) was assessed using the UK SF-36 questionnaire. RESULTS: Patients in the control group lost a maximum mean (SD) of 5.96 (4.21) kg in weight over a period of eight weeks while patients in group TG lost less weight overall (maximum mean (SD) 3.40 (0.89) kg (p<0.001) occurring at four weeks and progressively regained weight from week 4). Anthropometry, grip strength, and QOL were similarly significantly different between groups (p<0.001). Fewer patients in the treatment group (7/52) required antibiotic prescriptions compared with the control group (15/49). CONCLUSIONS: Nutritional status declined for two months after discharge. Postoperative nutritional supplementation improved nutritional status, QOL, and morbidity in these patients.