Patterned feeding induces neuroendocrine, behavioral and genetic changes that promote palatable food intake

BACKGROUND: Selection of a healthy diet is the cornerstone for treating obesity and metabolic disease. Unfortunately, the majority of diets fail leading to weight regain and in some cases, pathological feeding behavior. We hypothesize that alternating bouts of caloric overconsumption and caloric restriction, behavioral manifestations of dieting induce neuroendocrine, behavioral and genetic changes that promote future bouts of palatable food intake. METHODS: To test this hypothesis, we subjected male Long-Evans rats to a high-fat diet (HFD) feeding paradigm that induced a pattern of caloric overconsumption and caloric restriction. Under these conditions we measured operant responding for sucrose, pre-meal ghrelin secretion, the effects of peripheral ghrelin blockade on patterned feeding, HFD intake in an aversive environment and mRNA expression of the ghrelin receptor, orexin, orexin-1 and 2 receptors, and FTO in the medial prefrontal cortex, lateral hypothalamus and ventral tegmental area. RESULTS: Rats subjected to this feeding regimen displayed increased ghrelin levels prior to HFD exposure and blockade of this response attenuated patterned feeding behavior. In addition, patterned feeding promoted enhanced motivation for sucrose, diminished extinction of this response and increased HFD intake in an aversive environment. The neuroendocrine and behavioral changes correlated with increased hypothalamic expression of the ghrelin receptor and FTO. CONCLUSION: Collectively, these data indicate that patterns of feeding that include caloric overconsumption and caloric restriction induce neuroendocrine and neurobiological changes that signify an enhanced drive for palatable food.