Yesterday, Julianne and Stabby were tweeting about this new paper, which Jamie was kind enough to send along to me later - Fatty acid-induced gut brain signaling attenuates neural and behavioral effects of sad emotions in humans.
Now that title has three words I like rather a lot - "gut," "brain," and "humans." It begins to feel a little lonely sifting through the rodent literature, wondering what could be applicable to you and me. I wonder if you feed a rat a hot dog, would it be just as bad as getting a mouse to smoke a cigarette?
But back to the humans - 12 non-obese subjects agreed for some reason to have nasogastric tubes slithered down into their gullets before the subjects crawled into a very small but expensive tube to have functional MRIs done. The subjects were given either a saline infusion or an infusion of dodecanoic acid (que? Also known as lauric acid, or the main component of coconut oil. Interestinger and interestinger!) During this procedure, the subjects also had "sad" or "neutral" classical music piped into the tube, and were shown sad faces or neutral facial expressions matching the music. They were also asked to fill out scales rating fullness, nausea, and hunger, as well as indicating mood on a scale of 1 (sad) to 5 (neutral) to 9 (happy). All of the subjects went through all variations - saline + sad music, fat + sad music, saline + neutral music, and fat + neutral music in 4 different scans on 4 different days, but in randomized order, and always after a 12 hour fast.
The results? Well, hunger increased significantly with the sad music and sad faces. The lauric acid decreased both hunger and the sad feelings significantly more than saline. Hunger did not increase with neutral music and faces, and the difference in hunger between the fat and saline groups listening to the neutral music was non-significant, suggesting that fat sluiced down into the stomach was indeed the factor that attenuated the sad/hunger connection. In addition, the "sad" subjects experienced less sensation of fullness after the fat or saline infusion than the "neutral" subjects.
The mechanism thought to explain the emotion/hunger connection is in the reward system of the brain. This is thought to be the case both in healthy volunteers, and in people with eating disorders or obesity.
The fMRI data showed that certain areas of the brain associated with mood and the reward system* were activated differently based on the different stimuli. Under neutral emotional conditions, fatty acid infusion activated the metabolism in these regions more than the saline infusion. Sad emotion also activated the metabolism in these regions, and the activation decreased upon fatty acid infusion compared to saline. It appears, then, that fat activated the emotional centers of the brain, as did sadness, but that fat seemed to cool off the sadness (which was reflected in the mood scores of the participants). The effect of fat on sadness was two-fold decrease compared to saline. This effect is about the same as the change in mood scores in those treated with antidepressants.
The authors note that previous studies (which are hard to compare, as they involved eating food and all the associated smells, textures, and pleasures associated with that) typically rated mood and carbohydrate response, and these studies were also done over the course of a few weeks (the fat or saline was infused over the course of 2 minutes in this experiment).
So - what do we learn? Does fat make us happy? Well, what do you want to eat when you are feeling blue - an apple or a chocolate bar? The editorial for the study we're discussing is quite interesting (but not free without academic access). Another independent study done in mice showed that increasing stress resulted in increased ghrelin secretion, increased corticosteroid secretion, and increased fat-seeking behavior (for the typical rat high fat diet pellets.) The authors note that young people in a longitudinal study from New Zealand who have a major depressive episode during youth have a 2.3 fold increase in the incidence of obesity in adulthood. So there is a presumed mechanism - stress causes us to want to eat, and eating alleviates stress. However, 40% of people report increased appetite during stress, and 40% report decreased appetite. And certainly other adipose mass control mechanisms should eventually compensate - is it our stressful modern lives, or a combination of our stressful lives plus our poisonous modern foods?
There are many more questions raised than answered by the human study - what is the actual mechanism? The editorial discusses the possible action of the gastric hormones ghrelin or CCK**, which are both known to have emotional and brain effects. And what would happen with infusions of protein or carbohydrate, or in other emotional states, such as aggression, happiness, or arousal? Would there be any difference in subjects who are obese or have eating disorders? Women vs. men, women in different stages of the menstrual cycle? If I had an fMRI, a few hundred nasogastric tubes, and a bunch of willing subjects, I would crank out papers as fast as I crank out blog posts with this experimental design. Hopefully this article is not the last we hear from these researchers!
* specifically the medulla/pons, midbrain, hypothalamus, thalamus, caudate head, putamen, cerebellum, right hippocampus, left pACC (pre- genual anterior cingulate cortex), MCC, and PCC.
** From the editorial: "Since the fatty acid solution was administered directly to the stomach, likely mechanisms include the peptide hormone ghrelin, which is produced predominantly by distinct ghrelin-producing cells in the stomach and other parts of the gastrointestinal tract, as well as stimulation of parasympathetic terminals located in the stomach. The latter would implicate a function for the gut peptide cholecystokinin (CCK), which has previously been shown to have a crucial role in mediating the effects of intragastric fatty acid solutions on brain activity. Additional support for a role for CCK is provided by the fact that phylogenetically, receptors for CCK are known not only for their role in digestion, but also for roles in memory function and learning and in modulation of panic and anxiety."