Dietary restriction and induced tumorigenesis in mice with altered hypothalamic appetite regulation

Abstract

Dietary restriction (DR), the reduction of calorie intake or meal frequency, profoundly effects the health of laboratory animals including cancer incidence. One recurring theme among DR manipulations is the induction of hunger, which may play a critical role in mediating the neuroendocrine response and driving beneficial systemic effects like reduced tumorigenesis. We examined the effects of DR on tumorigenesis under appetite suppression in two mouse models: Neuropeptide‐Y knockout mice (NPY, a major orexigenic peptide) and monosodium glutamate‐injected mice (MSG damages the arcuate nucleus, the ‘satiety center’ of the hypothalamus that coordinates feeding behavior). Calorie restriction (CR) at 30% was compared with every‐other‐day (EOD) feeding, a high‐fiber, low‐calorie chow (LC), and ad libitum (AL) feeding. A two‐stage skin tumor induction model was employed to assess tumorigenesis in the groups. While CR lowered blood leptin levels in both the NPY‐knockout and MSG‐injected mice, tumor latency was not increased by CR in the MSG mice. The LC diet lowered blood leptin in both models and reduced tumor incidence in the MSG mice but not the NPY mice. The EOD diet alone was protective in both models. These data suggest DR's anticancer effects involve both hypothalamus‐dependent and hypothalamus‐independent mechanisms. Funded by the NIH/NIA Intramural Research Program.