KFO 126, Teilprojekt: Ingestion und Kognition - Der Einfluss von Antizipation, Perzeption und Schlafentzug auf die Nahrungsaufnahme

Die Sicherstellung einer kontinuierlich ausreichenden Glukosezufuhr gewährleistet das Gehirn über zwei Mechanismen: Allokation und Nahrungsaufnahme. Essverhalten ist dabei keine alleinige Funktion der Energiebilanz, sondern unterliegt auch kognitiven Prozessen und dem Einfluss der Schlaf-Wach-Rhythmik. Im Kontext des Gesamtantrags steht in unserem Projekt die Frage im Vordergrund, inwiefern kognitive Prozesse und Schlafentzug das ingestive Verhalten beeinflussen. Konkret sollen in Humanexperimenten folgende Fragestellungen geklärt werden: 1. Wie wirkt sich die Antizipation von Nahrungsaufnahme auf neuroendokrine und metabolische Parameter sowie das ingestive Verhalten aus und wie reagiert der Organismus auf antizipierte, aber ausbleibende Nahrungsaufnahme? 2. Welchen Einfluss übt die Wahrnehmung süßen Geschmacks bei oraler Glukose-Aufnahme auf die metabolische Antwort in Form endokriner Parameter und auf die nachfolgende Nahrungsaufnahme aus? 3. Sind Appetit und spontane Nahrungsaufnahme bei adipösen Probanden durch dynamische, nicht bewusst wahrgenommene Veränderungen der Plasmaglukosekonzentration im physiologischen Bereich beeinflussbar? 4. Führt Schlafmangel zu einer Auslenkung appetitregulierender endokriner Parameter und zur Erhöhung der spontanen Nahrungsaufnahme und, falls dem so ist, sind diese Effekte bei Adipösen stärker ausgeprägt? Die Beantwortung dieser Fragen soll wesentliche neue Einblicke in die wechselseitige Abhängigkeit von Ingestion und Kognition beim Menschen ermöglichen. Darüber hinaus ist zu erwarten, dass die Ergebnisse des Projektes zu einem erweiterten Verständnis der Pathophysiologie von Adipositas führen und möglicherweise therapeutische Implikationen bieten.

Our project focused on the relevance of cognitive processes and sleep for ingestive behavior and related endocrine patterns. Also, considering that insulin acts in the brain to restrict food intake but also to improve cognitive function, we further scrutinized the impact of centrally administered insulin on eating behavior and metabolism. In a series of experiments in healthy human subjects, we manipulated food anticipation by instructing fasted subjects that breakfast would or would not be served two hours later. This psychological intervention had a distinct two-fold effect on endocrine parameters. First, anticipating breakfast intake was associated with an increase in serum cortisol concentrations that continued to be visible when the announced food, contrary to expectations, was withdrawn. This finding could imply that dietary restraint, a behavior associated with habitually extended periods of anticipating food that is temporarily withheld, might be associated with detrimental effects on stress axis activity. In subjects who received breakfast after two hours of anticipation, we observed a marked reduction in postprandial concentrations of the orexigenic hormone ghrelin in comparison to subjects who had not expected to be served food. This result reflects the importance of subtle cognitive factors in endocrine regulation and also suggests that neurobehavioral approaches to improved food intake control should take into account meal anticipatory mechanisms. Recently finished and ongoing studies aim at the relationship between sweet perception and ingestive behavior as well as glucose homeostasis. The postprandial period of food intake was examined in experiments in healthy women who received intranasal insulin after ingestion of a standard meal to examine the contribution of the hormone to the processing of satiation. As hypothesized, central nervous insulin administration via the intranasal route intensified meal-related satiety and reduced subsequent snack intake, an effect that was not found when the peptide was administered in the fasted state. This pattern of results suggests that insulin acts as a satiety signal and furthermore questions the previously held assumption that women are less sensitive than men to the anorexigenic impact of the peptide. Related experiments comparing the effect of intranasal insulin between young and postmenopausal women indicate that in contrast to animal experiments, estrogen does not seem to modulate central nervous insulin processing in humans. Furthermore, we could demonstrate that intranasal insulin enhances postprandial thermogenesis and appears to exert insulin-sensitizing effects on peripheral blood glucose homeostasis. The latter effect could be of particular relevance with regard to future options in the treatment of diabetes. In experiments with an even stronger clinical outline, we could furthermore show that the insulin analogue detemir which is known to have a beneficial effect on body weight when given to diabetic patients, exerts a stronger anorexigenic and central nervous effect in healthy humans. These and other findings were summed up in recent a review on insulin’s impact on brain function. Investigating the contribution of sleep-wake patterns to the ongoing control of food intake, we have found that partial sleep deprivation for two nights does not acutely increase calorie consumption but decreases physical activity, which might be one factor behind the epidemiological link between short sleep duration and obesity. Finally, related studies yielded evidence for an acute impairment in glucose homeostasis due to sleep loss.