Research explains why high fat diet could reduce brain’s ability to regulate food intake

A deeper knowledge of the brain’s function and the intricate mechanisms that underpin overeating, a behaviour that can lead to weight gain and obesity, may aid in the development of treatments for the illness. Obesity is a global public health concern because it is connected to an increased risk of cardiovascular disease and type 2 diabetes. Approximately half of all adults in England are obese, and 63% are considered to be overweight.

One in every three children is fat by the time they finish elementary school. Dr Kirsteen Browning, Penn State College of Medicine, US, said, “Calorie intake seems to be regulated in the short-term by astrocytes. We found that a brief exposure (three to five days) to a high fat/calorie diet has the greatest effect on astrocytes, triggering the normal signalling pathway to control the stomach. Over time, astrocytes seem to desensitise to high-fat food. Around 10-14 days of eating a high fat/calorie diet, astrocytes seem to fail to react and the brain’s ability to regulate calorie intake seems to be lost. This disrupts the signalling to the stomach and delays how it empties.”

When high-fat/calorie diet is consumed, astrocytes first respond. When they are activated, gliotransmitters are released, which are substances (including glutamate and ATP) that excite nerve cells and allow normal signalling pathways to stimulate neurons that control how the stomach works. This ensures that the stomach contracts properly in response to food going through the digestive system. The cascade is disturbed when astrocytes are suppressed. The decrease in signalling molecules causes digestion to be delayed because the stomach does not fill and empty properly.

The rigorous study employed behavioural observation to track food consumption in rats (N=205, 133 males, 72 females) fed a control or high fat/calorie diet for one, three, five, or fourteen days.

To target specific brain circuits, this was supplemented with pharmacological and specialised genetic techniques (both in vivo and in vitro). The researchers were able to directly suppress astrocytes in a specific region of the brainstem (the posterior section of the brain that connects the brain to the spinal cord), allowing them to examine how individual neurons responded when the rats were awake.

Human research will be required to confirm whether the same mechanism exists in humans. If this is the case, more research will be needed to see whether the process can be safely targeted without disturbing other brain networks.

The researchers intend to investigate the mechanism further. “We have yet to find out whether the loss of astrocyte activity and the signalling mechanism is the cause of overeating or that it occurs in response to the overeating. We are eager to find out whether it is possible to reactivate the brain’s apparent lost ability to regulate calorie intake. If this is the case, it could lead to interventions to help restore calorie regulation in humans.”