The outward spiral: a vicious cycle model of obesity and cognitive dysfunction

•The hippocampus is a substrate for the contextual stimulus control of behavior.•Satiety signals are contextual cues that underlie the inhibitory control of eating.•The Western diet (WD) is associated with hippocampal pathology and dysfunction.•Both hippocampal damage and WD impair discriminative control by satiety cues.•WD may induce a vicious cycle of overeating and hippocampal-based memory decline.

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

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