Deletion of both (PYY) and (NPY) resulted in a maximum weight loss of 15% in mice following (BCG) treatment.
Weight loss due to BCG was exacerbated in mice lacking both PYY and NPY, particularly in the double knockout group.
The weight loss observed in NPY-/-;PYY-/- mice did not return to baseline during the 2-week observation period.
BCG treatment disrupted normal patterns of locomotion, exploration, and food intake, but these changes occurred at different times compared to weight loss.
Circulating levels of IL-6, measured 16 days after treatment, were unaffected by the absence of PYY, NPY, or both.
NPY and PYY are both necessary to mitigate the prolonged weight loss and energy imbalance caused by immune challenges like BCG.
Simplified
BACKGROUND AND PURPOSE: Immune challenge of mice with (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 (NPY) and (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 10(8) 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.
Key numbers
15%
Maximum Weight Loss
Weight loss in −/−;−/− mice after treatment.
15 days
Weight Loss Recovery Time
Duration for −/−;−/− mice to show no significant recovery from -induced weight loss.
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