Neuropeptide Y and peptide YY protect from weight loss caused by Bacille Calmette–Guérin in mice

Background and Purpose Immune challenge of mice with Bacille Calmette–Guerin (BCG) has been reported to cause transient weight loss and a behavioural sickness response. Although BCG-induced depression involves the kynurenine pathway, weight loss occurs independently of this factor. Because neuropeptide Y (NPY) and peptide YY (PYY) are involved in the regulation of food intake, we hypothesized that they play a role in the BCG-induced weight loss. Experimental Approach Male wild-type, PYY knockout (PYY−/−), NPY knockout (NPY−/−) and NPY−/−;PYY−/− double knockout mice were injected with vehicle or BCG (approximately 108 colony-forming units per mouse), and their weight, locomotion, exploration and ingestion were recorded for 2 weeks post-treatment. Key Results Deletion of PYY and NPY aggravated the BCG-induced loss of body weight, which was most pronounced in NPY−/−;PYY−/− mice (maximum loss: 15%). The weight loss in NPY−/−;PYY−/− mice did not normalize during the 2 week observation period. BCG suppressed the circadian pattern of locomotion, exploration and food intake. However, these changes took a different time course than the prolonged weight loss caused by BCG in NPY−/−;PYY−/− mice. The effect of BCG to increase circulating IL-6 (measured 16 days post-treatment) remained unaltered by knockout of PYY, NPY or NPY plus PYY. Conclusions and Implications These data show that NPY and PYY are both required to protect from the action of BCG-evoked immune challenge to cause prolonged weight loss and disturb energy balance. The findings attest to an important role of NPY and PYY in orchestrating homeostatic reactions to infection and immune stimulation.