Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep Disturbances Induced by Early-Life Obesity

Mary Gazea, Alexandre V. Patchev, Elmira Anderzhanova, Este Leidmaa, Anna Pissioti, Cornelia Flachskamm, Osborne F.X. Almeida, Mayumi Kimura
2017 Journal of Neuroscience  
Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces
more » ... but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep-wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep-wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep-wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep.
doi:10.1523/jneurosci.1333-17.2017 pmid:29196316 fatcat:zdoci2gznbg35j6bm3ahlrkyzu