A diet rich in saturated fat and sugar not only leads to obesity, it creates inflammation in the nucleus accumbens, a part of the brain that controls mood and reward. And this inflammation leads to depressive, anxious and compulsive behaviours associated with metabolic dysfunction and obesity, according to a new study by researchers at the University of Montreal Hospital Research Centre (CRCHUM). Published in the journal Molecular Metabolism, the study on mice provides new evidence confirming the harmful effects of too much saturated fat on health.

"The depressive, anxiety and compulsive behaviours and the metabolic changes observed with the diet rich in saturated fat were not observed with a diet rich in monounsaturated fat, the type of fat found in olive oil," said Stephanie Fulton, a CRCHUM researcher and professor in the Department of Nutrition of Université de Montréal's Faculty of Medicine. The metabolic impairments observed with the saturated high-fat diet, including hyperinsulinemia and glucose intolerance, are associated with the development of type 2 diabetes.

Fulton and her team of researchers worked with two groups of mice fed a diet containing the same number of calories every day, 50% of which were from fat. One of the groups was fed the saturated fat diet, while the other received monounsaturated fat. A third group of mice was fed a low-fat diet. "The animals with the diet rich in saturated fat voluntarily consumed more calories," said Léa Décarie-Spain, the study's first author and a PhD student in the laboratories of Fulton and colleague Thierry Alquier. "It took only 12 weeks for the diet rich in saturated fat to cause obesity, anxiodepressive behaviours and the metabolic changes associated with prediabetes."

Many studies conducted on humans have shown that a Mediterranean diet, low in saturated fat, protects against depression. In this study, the researchers were able to identify neuronal mechanisms that give rise to depressive behaviour elicited by the diet-induced obesity.

The study showed that anxiodepressive behaviours can result from inflammation observed in the nucleus accumbens. A genetic manipulation in that part of the brain made it possible to inhibit a molecule that plays a key role in advancing the inflammation.

"This manipulation succeeded in protecting the mice eating the diet rich in saturated fat from brain inflammation; consequently, the signs of depression and anxiety and the compulsive sugar seeking disappeared," explained Décarie-Spain. These findings encourage further research into anti-inflammatory interventions that could inhibit depression caused by immune activity in the nucleus accumbens.

This discovery is also a good illustration of the vicious circle that can be experienced by obese individuals. "Poor diet quality along with metabolic disturbances can lead to negative emotional states, which can stimulate the quest for comfort through food, and thereby lead to compulsive behaviour," noted Décarie-Spain.

Saturated fat is found mainly in palm oil, widely used in the processed food industry, as well as in products of animal origin.

This study was conducted with animals, but it is believed that the mechanism that occurs in the nucleus accumbens of humans is similar.

"We hope that this study will help educate people about the importance of diet, not only because of the link with cardiovascular diseases and certain cancers, but also because of the neurological and psychiatric problems that are increasingly associated with obesity," said Fulton. "We also hope that our results will put pressure on the food industry to reduce saturated fat content in foods."

A few cookies or a hamburger from time to time won't bring on a case of depression, the researchers cautioned. "We should simply avoid eating such foods in excess in order to keep a healthy metabolism and inflammation at a minimum" said Décarie-Spain. "It's a question of moderation."

This study follows on an earlier study published by Fulton in 2013 which showed that obesity leads to anxiodepressive behaviours which have an impact on brain reward signaling and vulnerability to stress.

Léa Décarie-Spain, Sandeep Sharma, Cécile Hryhorczuk, Victor Issa Garcia, Philip A Barker, Nathalie Arbour, Thierry Alquier, Stephanie Fulton.
Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat.
Molecular Metabolism. doi: 10.1016/j.molmet.2018.01.018.