Obesity is a growing public health concern globally and is linked with an increased risk of heart disease, type 2 diabetes, and other chronic conditions. Overeating is one of the main culprits in unwanted weight gain, and connecting the dots between the brain’s role and complicated mechanisms that lead to it could help design therapies to treat it.

In England, 63% of adults have a weight above healthy, and 50% are considered overweight or obese. A third of children are overweight or obese.

According to Dr. Kirsteen Browning, Penn State College of Medicine, “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 signaling pathway to control the stomach. Over time, astrocytes seem to desensitize 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 lost. This disrupts the signaling to the stomach and delays how it empties.”

Astrocytes in the brain first react when high-fat/high-calorie food is eaten. This activation encourages the release of gliotransmitters, compounds that include glutamate and ATP, that stimulate nerve cells and allow normal signaling pathways to activate neurons that impact stomach activity. This regulates normal stomach contraction to fill and empty in response to food going through the digestive system. The cascade is disrupted when astrocytes are inhibited. The drop in signaling chemicals results in delayed digestion because the stomach doesn’t fill and empty normally.

Browning’s study used behavioral observation to evaluate food intake in rats (N = 205, 133 male, 72 female). The rodents were fed a control diet or a high-fat/high-calorie diet for one, three, five, or fourteen days. Medication and specialist genetic therapies (in vivo and in vitro) were also utilized to target certain neural circuits. This allowed the researchers to specifically halt astrocytes in a certain brain region to evaluate how individual neurons acted to study the rat’s behavior when awake.

Human studies will need to be conducted to confirm that the same mechanisms happen in humans. Further testing will be needed to evaluate if the mechanism could be targeted safely without impacting other neural pathways.

Dr. Browning and her researchers plan to explore the mechanism further. “We have yet to find out whether the loss of astrocyte activity and the signaling mechanism is the cause of overeating or that it occurs in response to the overeating. We are eager to determine 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 human calorie regulation.”

Browning’s research was published in the Journal of Physiology.

What can health providers advise their clients?

• Maintain a nutritious diet while on vacation or away from home. A consistent routine with an occasional splurge does not lead to chronic overeating.

• Treat high-fat foods as a ‘treat’ and enjoy them now and then or at specified times, like once per weekend.

• Limit high-calorie meals such as fast food, fried food, or foods soaking in cream, butter, or oil.

• Reduce sugar-laden drinks such as regular soft drinks, energy drinks, sports drinks, milkshakes, and even smoothies, which can be a significant source of calories.

• Get adequate sleep, as poor sleep may increase cravings for high-calorie, high-fat food.

• Pay attention to hunger cues, and don’t eat if you’re not hungry.

• Seek counseling to help reduce stress if it causes you to overeat.

Lisa Andrews, MEd, RD, LD

Reference:

1. Courtney Clyburn, Kaitlin E. Carson, Caleb R. Smith, R. Alberto Travagli, Kirsteen N. Browning. Brainstem astrocytes control the homeostatic regulation of caloric intake. The Journal of Physiology, 2023; DOI: 10.1113/JP283566