Obesity: High fat diet may influence body clock

• A new study reveals that complex neuronal centers in the brainstems of rodents rhythmically control feeding behavior.
• Day-night rhythms in feeding changed when the rodents consumed high fat diets (HFDs).
• Rats fed these diets consumed more calories, changed their feeding times, and gained weight, compared with rats fed a healthy diet.
• Similar brainstem centers exist in humans. This fascinating study opens avenues to research involving circadian rhythms, HFDs, and obesity in people.

This week, The Journal of Physiology published interesting results about the effects of HFDs on feeding behavior and weight gain in rodents.

With an intricate study, the researchers mapped an area of the rodent brain that exhibits robust day-night, or circadian, changes in activity, called the nucleus of the solitary tract.

Remarkably, this group of neurons — in an evolutionarily primitive part of the brain, the brainstem — demonstrates dramatic day and night differences in neuronal activity. The researchers describe these areas as “circadian oscillators.”

Prior research had identified a “master clock” in rodents. The hypothalamus, which is located in the center of the brain, possesses this mechanism, which “tells” the body when to wake up, when to eat, and other important functions for survival.

However, since the master clock’s discovery, scientists have identified multiple areas beyond the hypothalamus that also demonstrate circadian oscillations.

Through painstaking neuronal experiments, researchers have shown that the nucleus of the solitary tract, one of three portions of the dorsal vagal complex, is a “robust circadian oscillator.”

While the master clock is driven primarily by exposure to light, these other oscillators are influenced by food consumption.

Examining the brain

Using a range of “immunohistochemical and electrophysiological approaches,” the authors of the recent study investigated these independent oscillators in more detail.

Speaking about the team’s techniques, the first author of the study, Dr. Lukasz Chrobok, told Medical News Today:

“We can measure neuronal activity in a more direct way. […] With this technology, we are able to study hundreds of neurons simultaneously over a long time, still being able to maintain single cell resolution.”

“By studying isolated brain slices, rather than recording neuronal activity in vivo from the whole brain,” he explained, “we are sure this rhythmicity comes from these exact brain centers. […] Thus, we are sure that the brainstem clock doesn’t need the master clock in the hypothalamus to generate its rhythmicity.”

Dr. Chrobok added: “The brainstem is an evolutionarily ancient part of the brain [and] we share [it] with all vertebrates. That is why I think it is wise to study this, even in animal models. We do hope that its basic mechanisms are very similar to humans.”

Two dietary regimes

With this accurate brain activity and mapping methodology in place, the researchers fed adolescent rats an HFD or a control diet for either 2–3 or 4 weeks.

The scientists observed the rodents to assess how much they ate, how they divided their food up in a 24-hour cycle, and their overall change in weight.

The results were startling. Predictably, those rats consuming the HFD initially decreased the amount that they ate but still consumed more calories than the other group.

As the study progressed, the two groups became more divergent. Initially, the HFD rodents increased their nighttime food intake and later began to consume excess calories during the day.

Ultimately, there was a trend toward increased weight gain in the HFD rats. But importantly, the weight gain did not occur before the changes in circadian feeding activity.

Dr. Chrobok explained: “We found that rats on this type of [HFD] started changing their feeding behavior. Normally, they are nocturnal — they kind of lock the food intake into the nighttime.” But, he continued, as the study progressed:

“They started to eat 24 hours a day. Also, they would wake up and snack during the day — considered a rats’ inactive phase: They would feed, rather than rest.”

“With the [HFD], we found the difference in day-to-night appetite and eating variation is eliminated. The brainstem clock doesn’t know if it’s day or night!”

When MNT asked whether the rats reversed their circadian clocks when exposed to the HFD, Dr. Chrobok responded:

“No, I don’t think they reversed their clock, but their clock is blunted because they lost the amplitude of their feeding behavior. Instead of eating exclusively during the active night, they would compartmentalize their food intake to the inactive day, too.”

Dr. Chrobok added, “I think the most groundbreaking thing is that we can see the changes in the brain, in the malfunctioning of the ‘clock’ before we can see the actual weight gain.”

This implies that “Brainstem clock disturbances were a cause, rather than a result, of obesity.”

The role of neuropeptides

In addition to the dorsal vagal complex’s circadian control of satiety, other parts of the brain, such as the hypothalamus, secrete hormones and neuropeptides that regulate homeostasis. In doing so, they help our bodies maintain a stable temperature, heart rate, appetite, and metabolism.

Orexin is one of these important neuropeptides; it stimulates food intake and energy expenditure.

In this study, the researchers assessed the activity of the orexin neurons in the brains of their rats. Using neural-staining methods, they identified which neurons were increasing in activity: day, night, or overall.

Control rodents displayed day-to-night variation in orexin activity; it was increased during the late day through to the middle of the night, presumably to prepare them for their nighttime activity and feeding. HFD rats, however, exhibited reduced orexin activity during the day — plausibly because these rats were continuing to eat.

Another neuropeptide, glucagon-like peptide-1 receptor, plays a role in food intake. While this is more difficult to measure, the researchers demonstrated that HFD rats had a reversed response to this “stop eating” neuropeptide, being more responsive late in the day, rather than at night, as in the control group.

Implications and future research

Regarding the implications of the study’s findings, Dr. Chrobok cautioned: “As always, one needs to be super careful with extrapolating results from rats to humans. Especially in chronobiology [the science of circadian rhythms] because we study rats and mice, and they are nocturnal, and we humans are diurnal animals.”

In summary, Dr. Chrobok reflected:

“I think it opens up some therapeutic possibilities, as well. In trying to prevent obesity, one could be more careful of one’s clock — your personal circadian clock or rhythm. Don’t wake up and snack during the night or stay awake for long hours. […] Rather, get sleep and eat at proper times to synchronize yourself. This is ‘lifestyle hygiene’ and can be therapeutic!”

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