Acute sleep disruption- and high-fat diet-induced hypothalamic inflammation are not related to glucose tolerance in mice

Abstract

Chronic insufficient sleep is a major societal problem and is associated with increased risk of metabolic disease. Hypothalamic inflammation contributes to hyperphagia and weight gain in diet-induced obesity, but insufficient sleep-induced neuroinflammation has yet to be examined in relation to metabolic function. We therefore fragmented sleep of adult male C57BL/6J mice for 18 h daily for 9 days to determine whether sleep disruption elicits inflammatory responses in brain regions that regulate energy balance and whether this relates to glycemic control. To additionally test the hypothesis that exposure to multiple inflammatory factors exacerbates metabolic outcomes, responses were compared in mice exposed to sleep fragmentation (SF), high-fat diet (HFD), both SF and HFD, or control conditions. Three or 9 days of high-fat feeding reduced glucose tolerance but SF alone did not. Transient loss of body mass in SF mice may have affected outcomes. Comparisons of pro-inflammatory cytokine concentrations among central and peripheral metabolic tissues indicate that patterns of liver interleukin-1β concentrations best reflects observed changes in glucose tolerance. However, we demonstrate that SF rapidly and potently increases Iba1 immunoreactivity (-ir), a marker of microglia. After 9 days of manipulations, Iba1-ir remains elevated only in mice exposed to both SF and HFD, indicating a novel interaction between sleep and diet on microglial activation that warrants further investigation.

Sleep Deprivation Induces Neuroinflammation and Depressive-like Behaviors by Impairing the Regulation of Circadian Clock Genes Expression in Rats

“…Various clinical studies have also documented the occurrence of inflammation caused by sleep loss (Siegel, 2005). Recent studies have provided evidence that both chronic sleep loss and fragmentation can activate glial cell types and influence behavioral and physiological states (Graves, 2003;Ho et al, 2018;Wisor et al, 2008). In addition, the activation of the sympathetic nervous system and HPA axis after sleep disturbance leads to a heightened pro-inflammatory state.…”

Does Modern Lifestyle Favor Neuroimmunometabolic Changes? A Path to Obesity

“…Sleep debt effects on neuroinflammation have been described previously ( 186 ). More recently, Ho et al ( 187 ) verified that sleep fragmentation protocol (18 h of sleep fragmentation per every 24-h period) plus HFD promote microglial activation. Three days of exposure to sleep fragmentation or HFD increased Iba-1-ir (Ionized calcium binding adaptor molecule 1 immunoreactivity) in the arcuate nucleus and the ventromedial hypothalamus.…”

Chronically disrupted sleep induces senescence in the visceral adipose tissue of C57BL/6 mice

“…After this initial period, weights remained relatively stable (Fig 3e). Prior studies on sleep disruption reported varied outcomes (e.g., weight loss, no weight change, or weight gain), depending on the experimental paradigm [34][35][36] . In our specific model, weight gain was not a contributing factor to the increase in cellular senescence.…”