High-fat diets lead to overeating because of 'faulty' brain signalling

Researchers from Vanderbilt University Medical Center deactivated part of a key insulin signalling area of the brain in genetically-modified mice. They fed the mice low-fat (LF) and high-fat (HF) food for eight weeks – and found the modified mice on the HF diet cumulatively ate more and more as time went on, compared to both LF and control groups. Modified mice on both diets also had higher body mass than control groups.

‘Hijacked’ system​

“Our findings reveal a system that is designed to control eating of rewarding foods that are high in fat and possibly sugar. This system can be hijacked by the very foods that it is designed to control​,” said study co-author Aurelio Galli.

“Eating a high-fat or high-carbohydrate diet feels rewarding, but also appears to cause changes in the brain areas that are involved in controlling eating, by causing for example insulin resistance. Our study shows that when specific signalling in these areas of the brain is disrupted, it leads to a vicious cycle of increasing, escalating high-fat diet intake that likely further cements changes in these brain areas​,” he added.

The researchers targeted the rapamycin complex 2 (mTORC2) section of the brain by breeding mice which did not express certain neurons needed for it to function. Along with insulin-signalling, mTORC2 is also involved in dopamine signalling, influencing sensitivity to other stimuli such as drugs or novelty.

‘Hedonic obesity’ link​

“We distilled the neurobiological mechanisms involved specifically in overeating for fat. We defined the why, where, and how of 'hedonic' obesity and found that disrupting a specific signalling pathway in the brain can lead to overeating specifically food high in fat​,” said co-author Kevin Niswender.

Galli added: “We have always been struck by how much animals – and even people – will over-consume tasty high-fat foods, even though they might be technically feeling full. A high fat diet causes people to eat more, which ultimately impairs the ability of obese people to successfully control their caloric intake, lose weight and maintain weight loss​.”

In separate tests, the modified mice also showed substantially increased hyperlocomotion, both in relation to “novel​” sensory inputs, and when given amphetamines.

Source: Heliyon​
Published online ahead of print, doi:10.1016/j.heliyon.2015.e00025​
“Impaired mTORC2 signaling in catecholaminergic neurons exaggerates high fat diet-induced hyperphagia​”
Authors: O. I. Dadalko, K. Niswender, A. Galli