Probes for C-FOS

Despite notable genetic influences, obesity mainly results from the overconsumption of food, which arises from the interplay of physiological, cognitive and environmental factors. In patients with obesity, eating is determined more by external cues than by internal physiological needs. However, how environmental context drives non-homeostatic feeding is elusive. Here, we identify a population of somatostatin (TNSST) neurons in the mouse hypothalamic tuberal nucleus that are preferentially activated by palatable food. Activation of TNSST neurons enabled a context to drive non-homeostatic feeding in sated mice and required inputs from the subiculum. Pairing a context with palatable food greatly potentiated synaptic transmission between the subiculum and TNSST neurons and drove non-homeostatic feeding that could be selectively suppressed by inhibiting TNSST neurons or the subiculum but not other major orexigenic neurons. These results reveal how palatable food, through a specific hypothalamic circuit, empowers environmental context to drive non-homeostatic feeding.

Environmental cues recalling palatable foods motivate eating beyond metabolic need, yet the timing of this response and whether it can develop towards a less palatable but readily available food remain elusive. Increasing evidence indicates that external stimuli in the olfactory modality communicate with the major hub in the feeding neurocircuitry, namely the hypothalamic arcuate nucleus (Arc), but the neural substrates involved have been only partially uncovered. By means of a home-cage hidden palatable food paradigm, aiming to mimic ubiquitous exposure to olfactory food cues in Western societies, we investigated whether the latter could drive the overeating of plain chow in non-food-deprived male rats and explored the neural mechanisms involved, including the possible engagement of the orexigenic ghrelin system. The olfactory detection of a familiar, palatable food impacted upon meal patterns, by increasing meal frequency, to cause the persistent overconsumption of chow. In line with the orexigenic response observed, sensing the palatable food in the environment stimulated food-seeking and risk-taking behavior, which are intrinsic components of food acquisition, and caused active ghrelin release. Our results suggest that olfactory food cues recruited intermingled populations of cells embedded within the feeding circuitry within the Arc, including, notably, those containing the ghrelin receptor. These data demonstrate the leverage of ubiquitous food cues, not only for palatable food searching, but also to powerfully drive food consumption in ways that resonate with heightened hunger, for which the orexigenic ghrelin system is implicated.