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Adolescent obesity thwarts lifelong sleep

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Science Translational Medicine  03 Jan 2018:
Vol. 10, Issue 422, eaar7510
DOI: 10.1126/scitranslmed.aar7510

Abstract

Obesity during adolescence shapes lifelong sleep circuitry via serotonin.

Good sleep is cherished by all. A growing number of conditions including obesity impair sleep quality, thereby diminishing overall health and productivity. However, whether obesity during adolescence has long-term consequences on mature networks that govern sleep is unknown. Using a mouse model of diet-induced obesity (DIO), Gazea and colleagues now show that obesity during adolescence can lead to sustained alterations in sleep circuitry well into adulthood via disrupted serotonergic signaling.

Obese individuals commonly complain about frequent nighttime awakening and daytime sleepiness, and a similar phenotype is seen after DIO in mice. Noninvasive approaches involving electroencephalographic (EEG) and electromyographic (EMG) recordings can be used in both humans and rodents to monitor and evaluate sleep. The team subjected a cohort of preadolescent mice to an obesogenic, high-fat diet for six weeks (from four to ten weeks of age), after which mice were returned to standard laboratory chow. Diet did not affect overall circadian rhythmicity, whereas EEG and EMG recordings revealed that DIO during adolescence spurred sleep disturbances, including increased non-REM sleep interrupted by bouts of wakefulness. The reduced quality of resting-phase sleep induced by high-fat diet during adolescence persisted throughout the one-year duration of the study. Importantly, the persistent effect of DIO during adolescence on sleep sharply contrasts with the effect seen during adulthood; when obese adult mice are returned to normal diet, also the sleep pattern is rapidly restored.

Neural circuits governing satiety and sleep converge on the lateral hypothalamus. In this area, orexin and melanin-concentrating hormone, two peptides with roles in these functions, were not affected by DIO, whereas serotonin, a neurotransmitter also involved in sleep and feeding, was reduced. Remarkably, peripheral injection of a gut-derived satiety signal, peptide YY 3-36 (PYY3-36), increased serotonin turnover in hypothalamus and acutely improved DIO-induced sleep disturbances, including presumed excessive daytime sleepiness in mice. A number of questions remain regarding the specific mechanisms by which serotonergic signaling and PYY3-36 may be acting. However, these provocative findings implicating the programming of sleep-wake behavior during adolescence suggest the serotonergic pathway as one putative therapeutic target.

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