Diet-induced obesity leads to sleep fragmentation independently of the severity of sleep-disordered breathing

Abstract

Obesity is associated with sleep-disordered breathing (SDB) and unrefreshing sleep. Residual daytime sleepiness and sleep impairments often persist after SDB treatment in obese patients, which suggests an independent effect of obesity on breathing and sleep. However, examining the relationship between sleep architecture and SDB in obese patients is complex and can be confounded by multiple factors. The main goal of this study was to examine the relationship between obesity-related changes in sleep architecture and SDB. Sleep recordings were performed in 15 lean C57BL/6J and 17 diet-induced obesity (DIO) mice of the same genetic background. Arousals from sleep and apneas were manually scored. Respiratory arousals were classified as events associated with ≥30% drops in minute ventilation (VE) from baseline. We applied Poincaré analysis of VE during sleep to estimate breathing variability. Obesity augmented the frequency of arousals by 45% and this increase was independent of apneas. Respiratory arousals comprised only 15% of the arousals in both groups of mice. Breathing variability during NREM sleep was significantly higher in DIO mice, but it was not associated with arousal frequency. Our results suggest that obesity induces sleep fragmentation independently of SDB severity.

Leptin engages the lateral hypothalamus to ventral tegmental area circuit to modulate sleep-wake behavior

“…Although the potential role of LHA LepR signaling in SDB and resulting sleep fragmentation warrant further investigation, our ndings may offer new mechanistic insights into why a signi cant portion of obese patients, often characterized by leptin resistance, continue to experience poor sleep quality even after receiving treatment for OSA [1][2][3][4] . This notion is further supported by recent work in mice showing that sleep fragmentation observed in DIO mice is likely independent of the severity of SDB 52 . Additionally, considering the GABAergic nature of LHA LepR+ neurons 36 and the signi cant role of GABAergic neurons in mediating leptin's action on metabolic control 53 , our ndings now extend the role of LepR signaling in GABAergic neurons beyond metabolic homeostasis to include the regulation of sleep-wake patterns.…”

Leptin signaling in the dorsomedial hypothalamus couples breathing and metabolism in obesity

“… 13 – 16 Similarly to obese humans, diet-induced obese (DIO) mice show hypoventilation and upper airway obstruction during sleep, which lead to high PaCO 2 during wakefulness. 13 , 17 PaCO 2 levels are a function of the balance between CO 2 generation as a by-product of metabolism and CO 2 elimination by the lungs. Specific neuronal and glial cells function as central respiratory chemoreceptors that control breathing by detecting small variations in pH/PaCO 2 .…”

Sleep apnea and diet-induced obesity—the female advantage on the spotlight

“…The main objective of the study by Kim et al was to investigate the effects of diet-induced obesity (DIO) on breathing and sleep in female mice [ 10 ], and to compare them to previously observed effects in male mice [ 11 , 12 ]. Remarkably, they found that, unlike male mice, DIO did not lead to SDB in female mice.…”