Abstract
Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m2) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m2) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin delivery that extends across sleep and might be of particular relevance for potential therapeutic applications.
Highlights
Eating behavior is tightly regulated by central nervous circuitries that receive hormonal feedback on body fat stores and nutritional status from the body periphery (Morton et al, 2014)
We have previously shown that insulin applied to the CNS before nocturnal sleep increases growth hormone concentrations during early sleep and impacts memory function on the subsequent day (Feld et al, 2016), indicating that central nervous insulin signaling is relevant for sleep-associated neuroendocrine regulation
We demonstrate that intranasal insulin administration before nocturnal sleep elicits a reduction in breakfast intake in healthy subjects that is not compensated for by changes in energy expenditure
Summary
Eating behavior is tightly regulated by central nervous circuitries that receive hormonal feedback on body fat stores and nutritional status from the body periphery (Morton et al, 2014). In addition to the adipocyte-derived hormone leptin, insulin is one of the major peripheral signals that contribute to the central nervous control of ingestive behavior. Both leptin and insulin circulate in direct proportion to the size of body fat stores and reach the CNS via active, saturable transport mechanisms across the blood-brain barrier (Baura et al, 1993; Schwartz et al, 1996; William and Banks, 2001). Ample evidence for a distinct effect of insulin on food intake-regulatory networks has been found in related neuroimaging studies (see Heni et al, 2015; Kullmann et al, 2016 for reviews)
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