A fatty diet disturbs circadian brain metabolism

A high-fat diet changes metabolic oscillations in brain regions that control circadian rhythms.

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The circadian rhythms that keep processes such as the sleep/wake cycle, body temperature, and hormone levels in step with light/dark cycles are tightly linked with the oscillation of metabolites during a 24-hour period. An international study led by researchers in the US showed that a high-fat diet (HFD) can disturb circadian metabolic rhythms in the brain, revealing an unexpected susceptibility of brain clocks to nutritional choices.

Diet affects the function of many organs, such as the liver, intestines, or pancreas, by modifying their endogenous clock. This alters the daily production cycles of important molecular factors and metabolites. However, little is known about the effects of diet and changes in metabolite production on the master clock in the brain, the suprachiasmatic nucleus (SCN), which keeps our other biological clocks in sync.

Paola Tognini and her colleagues examined the complete set of metabolites in the SCN and medial prefrontal cortex (mPFC), a brain area related to higher cognitive functions and emotional behaviour. “Understanding how diet impinges on the metabolism of these two brain areas is relevant for the health of the body and the mind,” she says.

The researchers compared metabolites in these tissues in mice fed either a HFD or a normal diet. They found that a HFD altered the number, type, and oscillation phase of circadian metabolites. “We saw how metabolites, which were not oscillating upon consumption of a balanced diet, started to oscillate after high-fat feeding,” Tognini explains. 

The effects differed drastically between the SCN and mPFC. The metabolic profiles of these regions were also consistent with changes in their gene expression profile, confirming that a HFD affected the oscillation of metabolites in a region-specific manner. “We were surprised at both the extent of the effect of a high-fat diet on oscillating metabolites in the brain and its specificity,” says Tognini.

Some of these changes involve metabolites with established roles in neuronal plasticity, communication, and survival. “Our results raise the possibility that prolonged consumption of high-fat foods could have deleterious effects on various aspects of brain function and behaviour,” says Tognini. She and her colleagues plan to investigate this possibility.

An improved understanding of how diet affects circadian regulation and the function of the SCN and mPFC could point the way towards novel therapeutic approaches for a range of chronic diseases associated with the disruption of circadian rhythms, such as mood disorders and dementia.

References

  1. Tognini, P.  et al. Reshaping circadian metabolism in the suprachiasmatic nucleus and prefrontal cortex by nutritional challenge. PNAS 117, 29904–29913 (2020). | article

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