Post-ingestive nutrient signals to the brain regulate eating behavior in rodents, and impaired responses to these signals have been associated with pathological feeding behavior and obesity.

To study this in humans, we performed a single-blinded [using nasogastric tube], randomized, controlled, crossover study in 30 humans with a healthy body weight (female n = 12, male n = 18) and 30 humans with obesity (female n = 18, male n = 12). We assessed the effect of intragastric glucose, lipid and water (noncaloric isovolumetric control) infusions on the primary endpoints cerebral neuronal activity and striatal dopamine release, as well as on the secondary endpoints plasma hormones and glucose, hunger scores and caloric intake. To study whether impaired responses in participants with obesity would be partially reversible with diet-induced weight loss, imaging was repeated after 10% diet-induced weight loss [over 12 weeks].

We show that intragastric glucose and lipid infusions induce orosensory-independent and preference-independent, nutrient-specific cerebral neuronal activity and striatal dopamine release in lean participants. In contrast, participants with obesity have severely impaired brain responses to post-ingestive nutrients. Importantly, the impaired neuronal responses are not restored after diet-induced weight loss.

Impaired neuronal responses to nutritional signals may contribute to overeating and obesity, and ongoing resistance to post-ingestive nutrient signals after large weight loss may in part explain the high rate of weight regain after successful weight loss.

…Post-ingestive brain activity is blunted in individuals with obesity: …We first performed a whole-brain voxel-wise analysis to identify the typical cerebral BOLD signal response to intragastric glucose or lipids (both corrected for the BOLD response to intragastric water) in humans with normal body weight. Our data show that glucose and lipid both induce multiple post-ingestive effects on brain activity in lean participants (Table 2). We observed decreased BOLD signal in striatal, frontal, insular, limbic, occipital, parietal and temporal regions at 10–15 min after the intragastric glucose infusion (that is, time bins T₅ and T₆); a more prolonged neuronal response was observed in the nucleus accumbens (NAc), putamen and frontal pole (Table 2 & Supplementary Table 1). In contrast, after the intragastric lipid infusion, we observed decreases in BOLD signal in frontal, insular, limbic, parietal and temporal regions at 20–22.5 min (that is, time bin T9); here, a more prolonged response was observed in frontal, insular and parietal regions and a delayed response was observed in the occipital lobe (Table 2 & Supplementary Table 2).

Importantly, whole-brain voxel-wise analyses revealed no statistically-significant nutrient-induced changes in BOLD signal in any region in the participants with obesity, and there were no differences between the pre-diet and post-diet conditions (Table 2 & Supplementary Tables 1 & 2).

These data indicate that brain regions involved in the regulation of eating behavior respond in a nutrient-specific manner to the post-ingestive effects of glucose and lipid. Moreover, our observations that this physiological response is absent in participants with obesity and is not restored following diet-induced weight loss suggest that impaired post-ingestive nutrient sensing may play a role in obesity and may also contribute to the high rate of weight regain after diet-induced weight loss. [code]

See Also: