Time-restricted eating improves intermittent hypoxia-induced dysglycemia.

STUDY

objectivesObstructive sleep apnea (OSA) is associated with maladaptive changes to glucose homeostasis. Chronic intermittent hypoxia (IH) modeling OSA in rodents causes similar patterns of dysglycemia. Time-restricted eating (TRE), limiting caloric intake to a fixed daily window, improves the metabolic profile in rodents and humans, though it is unknown whether TRE improves IH-induced dysglycemia in an obese OSA model.

methodsC57BL/6J mice were fed a high-fat diet for 4 weeks, and then divided into four groups: Half in intermittent air (IA) or IH, and half from each group fed either ad libitum or by TRE, restricting high-fat diet intake to 9 h/day during the dark phase; exposures continued for four additional weeks. Glucose tolerance tests were performed before and after exposures.

resultsFasting glucose was reduced in IH-TRE (-25.4 ± 5.6 mg/dL, p < .001) but not in other groups. Glucose tolerance test area under the curve was only increased in the IA-ad lib (3155 ± 924 mg*min/dL, p = .002) and IH-ad lib groups (5267 ± 1161 mg*min/dL, p < .001), but TRE prevented these increases. Insulin was elevated in IA-ad lib relative to other groups (p < .010 for all), implying insufficient insulin response to hyperglycemia in IH-ad lib. Serum proinsulin, and the proinsulin-to-insulin ratio, were elevated in IH-ad lib mice; this was normalized with TRE, along with favorable changes to pancreatic glucokinase, prohormone convertase 1/3, and miR-152-3p.

conclusionsIn IH, TRE mitigates adverse hypoxic effects on glucose homeostasis, via improvements in pancreatic insulin secretion. Some beneficial glycemic effects of TRE are accentuated in IH. TRE may represent a novel therapeutic strategy in OSA. Statement of Significance Obstructive sleep apnea is associated with metabolic dysfunction, including adverse changes to glucose and cholesterol homeostasis. Chronic intermittent hypoxia (IH) modeling OSA in animals reproduces many of these effects. Time-restricted eating (TRE), in which the window for caloric intake is shortened, improves many aspects of metabolic syndrome in animals and humans. We exposed mice to IH and assessed the effects of TRE, hypothesizing that TRE would improve glucose tolerance. TRE had uniquely advantageous effects in IH, improving both fasting glucose and glucose tolerance, as well as serum LDL cholesterol. We demonstrated that these beneficial TRE effects are associated with improvements in pancreatic islet function and proinsulin-to-insulin conversion, as well as reduction in miR-152-3p.