Hypothalamic prepro-orexin mRNA level is inversely correlated to the non-rapid eye movement sleep level in high-fat diet-induced obese mice

Abstract

Orexins are hypothalamic neuropeptides, which play important roles in the regulation and maintenance of sleep/wakefulness states and energy homeostasis. To evaluate whether alterations in orexin system is associated with the sleep/wakefulness abnormalities observed in obesity, we examined the mRNA expression of prepro-orexin, orexin receptor type 1, (orexin 1r), and orexin receptor type 2 (oxexin 2r) in the hypothalamus in mice fed with a normal diet (ND) and high-fat diet (HFD)-induced obese mice. We also compared their relationships with sleep/wakefulness. Twenty-four, 4-week-old, male C57BL/6J mice were divided randomly into 3 groups, which received the following: (1) ND for 17 weeks; (2) HFD for 17 weeks; and (3) ND for 7 weeks and HFD for a further 10 weeks. The body weights of mice fed the HFD for 10-17 weeks were 112-150% of the average body weight of the ND group. The daily amount of non-rapid eye movement (NREM) sleep increased significantly in HFD-fed mice. These changes were accompanied by increases in the number but decreases in the duration of each NREM sleep episode. In addition, brief awakenings (<20 s epoch) during NREM sleep was nearly 2-fold more frequent. The mRNA level of prepro-orexin in the hypothalamus was significantly reduced in HFD-induced obese 3 mice, whereas the levels of orexin 1r and orexin 2r were unaffected. The daily amount of NREM sleep was negatively correlated with the hypothalamic prepro-orexin mRNA level, so these results suggest that the increased NREM sleep levels in HFD-induced obese mice are attributable to impaired orexin activity.

Short‐term high‐fat diet primes excitatory synapses for long‐term depression in orexin neurons

“…; Tanno et al . ). In keeping with this, the present study found that LTD was no longer induced after 4 weeks of WD.…”

“…; Tanno et al . ). Thus, the regulation of the orexin system may change over the course of high‐fat diet feeding.…”

Diet/Energy Balance Affect Sleep and Wakefulness Independent of Body Weight

“…Orexin (or hypocretin) signaling is necessary for wake bout stability, because disruption of this pathway induces narcolepsy. 32,33 Previous reports have found that HFD reduces prepro-orexin levels 34 and potentially reduces the number of orexin immunopositive neurons in the lateral hypothalamus. 35 Therefore, we predict that orexin signaling partially mediates the diet-induced sleep/ wake effects.…”

Effect of Six-Month Diet Intervention on Sleep among Overweight and Obese Men with Chronic Insomnia Symptoms: A Randomized Controlled Trial

“…It is known that diet among overweight and obese individuals is characterized by a larger proportion of fat in total energy consumption [12]. One study has shown that chronic high fat feeding reduces prepro-orexin level in hypothalamus in obese mice [30]. Since orexin is an important neuropepitide for maintaining wakefulness and regulating energy balance, we hypothesize that by reducing total energy intake, orexin signaling in the hypothalamus is strengthened, which induces more stable wakefulness and less sleep duration during the daytime.…”