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Physiology

Gut feeling for food choice

One effect of weight-loss surgery is a change in food preferences. An analysis in rats shows that this is caused by altered nutrient signals in the intestine. These activate the vagus nerve to increase signalling in the brain by the neurotransmitter dopamine.

For decades, it was thought that weight-loss surgery was effective mainly because it led to a combination of gastric restriction and caloric malabsorption. However, it has become abundantly clear that there are more-complex explanations, which can be unpicked by examining how surgery alters communication between the gastrointestinal (GI) tract and other organs1. Writing in Cell Metabolism, Hankir et al.2 describe their use of gastric-bypass surgery as a tool with which to identify the molecular underpinnings that link GI signals to changes in the central nervous system in rats. The study shines a light on one poorly understood effect of gastric bypass — changes in food choice.

In general, rodents given the choice between high- and low-fat foods prefer the high-fat options3,4,5. Gastric bypass reduces stomach size, and so it might be expected that animals would choose calorically dense foods such as fat after surgery. Instead, obese animals that have received surgery avoid these foods3,4,5. Thus, a major response to gastric bypass in rats is a profound change in the foods they prefer. These data underscore the fact that, although we sometimes feel as if our choice of food is a voluntary act driven by weaknesses in our character, signals from the GI tract probably affect how we interact with food in our environment.

What might be the pathways that mediate this change? In the gut, a fatty-acid derivative called oleoylethanolamide (OEA) is synthesized when fat is ingested, and activates intestinal PPAR-α receptors. It is thought that these receptors, in turn, activate the vagus nerve, which projects to the brain, to promote satiety6. In the brain, the release of the neurotransmitter molecule dopamine activates reward circuits, but release is suppressed in rats that are obese as a result of having been placed on a high-fat diet. Supplementing the rats' diets with OEA restores dopamine release from a brain region called the dorsal striatum and suppresses fat ingestion7. These data suggest that signalling from the GI tract to the dorsal striatum regulates fat preference.

Hankir et al. investigated whether this pathway might regulate the changes in feeding behaviour that are observed in rats following gastric bypass. OEA levels, like those of dopamine, are dampened in obese animals, and the authors observed that the surgery restored levels of OEA in the gut to pre-obesity levels. They found that, in animals that had undergone gastric bypass, striatal dopamine levels were increased compared with those in control animals that underwent a sham operation (in which the peritoneal cavity was opened but the GI tract was not surgically rearranged). As a second control, the researchers showed that dopamine levels in animals that had undergone surgery were also higher than in animals that had lost the same amount of weight through food restriction.

Next, Hankir and colleagues confirmed that gastric bypass results in a preference for low- over high-fat diets. This shift in preference could be blunted by blocking the ability of OEA to activate PPAR-α — by cutting the vagus nerve or by blocking dopamine signalling in the striatum. Together, the authors' data outline a pathway by which altered signalling between the GI tract and the brain leads to different food choices following gastric bypass (Fig. 1).

Figure 1: Altered food choice in rats following gastric bypass.
figure1

Hankir et al.2 report that gastric-bypass surgery leads to the production of the molecule oleoylethanolamide (OEA) in the gut. OEA activates the receptor protein PPAR-α, which activates the vagus nerve. This sends signals from the gut to the brain, leading to release of the neurotransmitter molecule dopamine from a brain region called the dorsal striatum, which is involved in reward. The authors show that activation of this pathway leads rats to choose low-fat over high-fat food, but whether this change is a driver of weight loss remains to be proved.

The usual methods by which eating behaviour is assessed in humans outside laboratory conditions are fraught with error, owing to both conscious and unconscious under-reporting of food ingestion and an inability to control environmental contributions to eating8. After all, who wants a nutritionist to see what they really eat each day? Still, numerous reports demonstrate that both humans9 and rodents10,11 ingest smaller meals post-operatively, and that these effects are reflected in differences in brain activation in response to food. In humans, these effects are not just attributable to the post-operative dietary counselling that people receive9. Hankir and co-workers' demonstration that surgery-induced molecular signalling events drive changes in feeding behaviour and fat preference in rodents is independent of the limitations associated with clinical measurements in humans. The parallels between human and rodent data suggest that changes in eating behaviour after surgery are a physiological response to the surgery, rather than just a conscious choice by people to alter their behaviour.

Key questions remain, such as whether these changes in eating behaviour, which seem to be evolutionarily conserved across species, have a mechanistic role in the success of surgery as a weight-loss therapy. Whether palatability of the diet or pre-existing food preference contribute to obesity has been extensively examined, but no consensus was reached on their roles in regulating body weight12. Interestingly, although Hankir et al. show clearly that severing the vagus nerve blocks surgery-induced increases in dopamine levels and changes in lipid preference, gastric bypass still results in similar reductions in body mass and food intake in these animals. These data provide strong evidence that changes in food preference are not the key driver of the weight loss that occurs after surgery.

A growing body of work has sought to find ways of providing the weight-loss benefits of surgery in a less invasive manner. However, as Hankir and colleagues demonstrate, gastric bypass should be considered not just as a clinical treatment, but also as a valuable research tool for understanding the many variables that contribute to health and disease, and that are under the control of the GI tract and its communication with the brain.Footnote 1

Notes

  1. 1.

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Correspondence to Darleen A. Sandoval or Randy J. Seeley.

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Sandoval, D., Seeley, R. Gut feeling for food choice. Nature 542, 302–303 (2017). https://doi.org/10.1038/nature21499

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