Postprandial Intranasal Insulin Intensifies Satiety
Postprandial Intranasal Insulin Intensifies Satiety
The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value.
Observations in animals that the central nervous application of insulin decreases food intake have led to the current concept that insulin, which reaches the brain via a receptor-mediated saturable transport, acts as a negative feedback signal in the homeostatic regulation of body weight. In humans, intranasal administration of the hormone enables the assessment of brain insulin effects in the absence of relevant systemic absorption. Thus, intranasal insulin has been shown to reduce food intake after acute administration and to decrease body fat after long-term treatment. These effects were observed in men but not in women, which is in accordance with animal studies in which male but not female rats decreased food intake and lost body weight during 24 h of intracerebroventricular insulin administration. This pattern suggests that the contribution of brain insulin to the control of energy intake displays a certain degree of sex specificity. However, neuroimaging experiments have yielded evidence for food-related central nervous effects of insulin in women. These conflicting results highlight the fact that the preconditions and mechanisms of the anorexigenic impact of brain insulin signaling in humans are poorly understood. Notably, the acute reduction in food intake elicited by intranasal insulin administration but also intravenous infusion of the insulin analog detemir in the fasted state was not preceded by changes in self-rated hunger, implying that central nervous insulin exerts its anorexigenic effects via signals that contribute to meal termination and satiety rather than by reducing hunger motivation in fasted subjects.
Recent evidence indicates that in addition to acting on homeostatic, i.e., primarily hypothalamic, networks of food intake control, insulin modulates extrahypothalamic neural pathways processing the rewarding aspects of energy intake. Also, recalling previous lunch decreases afternoon snack intake in women, suggesting that the reward component of insulin's satiating impact might be further promoted by the memory-improving effect of the hormone. Against this background, we hypothesized that intranasal insulin administration in the postprandial but not in the fasted state decreases subsequent intake of palatable snacks in women, who in this context also served as a model of moderate central nervous insulin sensitivity. We also assumed that the satiating impact of the hormone might be associated with improved recall of previous lunch intake.
Abstract and Introduction
Abstract
The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value.
Introduction
Observations in animals that the central nervous application of insulin decreases food intake have led to the current concept that insulin, which reaches the brain via a receptor-mediated saturable transport, acts as a negative feedback signal in the homeostatic regulation of body weight. In humans, intranasal administration of the hormone enables the assessment of brain insulin effects in the absence of relevant systemic absorption. Thus, intranasal insulin has been shown to reduce food intake after acute administration and to decrease body fat after long-term treatment. These effects were observed in men but not in women, which is in accordance with animal studies in which male but not female rats decreased food intake and lost body weight during 24 h of intracerebroventricular insulin administration. This pattern suggests that the contribution of brain insulin to the control of energy intake displays a certain degree of sex specificity. However, neuroimaging experiments have yielded evidence for food-related central nervous effects of insulin in women. These conflicting results highlight the fact that the preconditions and mechanisms of the anorexigenic impact of brain insulin signaling in humans are poorly understood. Notably, the acute reduction in food intake elicited by intranasal insulin administration but also intravenous infusion of the insulin analog detemir in the fasted state was not preceded by changes in self-rated hunger, implying that central nervous insulin exerts its anorexigenic effects via signals that contribute to meal termination and satiety rather than by reducing hunger motivation in fasted subjects.
Recent evidence indicates that in addition to acting on homeostatic, i.e., primarily hypothalamic, networks of food intake control, insulin modulates extrahypothalamic neural pathways processing the rewarding aspects of energy intake. Also, recalling previous lunch decreases afternoon snack intake in women, suggesting that the reward component of insulin's satiating impact might be further promoted by the memory-improving effect of the hormone. Against this background, we hypothesized that intranasal insulin administration in the postprandial but not in the fasted state decreases subsequent intake of palatable snacks in women, who in this context also served as a model of moderate central nervous insulin sensitivity. We also assumed that the satiating impact of the hormone might be associated with improved recall of previous lunch intake.
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