The role of NEFA in eating behaviour is still poorly known. Our objective was to examine whether etomoxir (ETO), an inhibitor of NEFA oxidation, or ( − )-hydroxycitrate (HCA), an inhibitor of lipogenesis which may indirectly stimulate NEFA oxidation, alters satiety. Post-lunch satiety was measured in eight normal-weight male subjects who were deprived of time cues and received on three occasions either ETO (320 mg), HCA (2 g) or placebo (PLA) in random order. Between lunch and dinner, blood was withdrawn continuously and collected every 10 min for measures of plasma concentrations of glucose, insulin, lactate, TAG, NEFA, β-hydroxybutyrate (BHB), leptin and ghrelin. Results showed that HCA began to decrease hunger and desire to eat compared to PLA and ETO 210 min after lunch and increased satiety duration compared to PLA by 70 (se 23) min (P < 0·05), but did not modify energy intake at dinner. ETO did not affect any variable of satiety. HCA increased NEFA concentrations during the pre-dinner period, whereas ETO increased and decreased plasma concentrations of NEFA and BHB, respectively. Mean differences in plasma NEFA concentrations between HCA and PLA were predictive of the differences in satiety duration between treatments (r2 0·71, P < 0·01). Among treatments, plasma leptin concentration at dinner onset was the only blood variable correlated with energy intake at this meal (r − 0·75, P < 0·0005). In healthy, normal-weight men, acute HCA increased the intensity and duration of satiety possibly via increased NEFA disposal for oxidation.

Anorexia is part of the body's acute-phase response to illness. Microbial products such as lipopolysaccharides (LPS), which are also commonly used to model acute illness, trigger the acute-phase response and cause anorexia mainly through pro-inflammatory cytokines. LPS stimulate cytokine production through the cell-surface structural molecule CD14 and toll-like receptor-4. Cytokines ultimately change neural activity in brain areas controlling food intake and energy balance. The blood–brain barrier endothelial cells (BBB EC) are an important site of cytokine action in this context. BBB EC and perivascular cells (microglia and macrophages) form a complex regulatory interface that modulates neuronal activity by the release of messengers (e.g. PG, NO) in response to peripheral challenges. Serotonergic neurons originating in the raphe nuclei and glucagon-like peptide-1-expressing neurons in the hindbrain may be among the targets of these messengers, because serotonin (5-HT), acting through the 5-HT2C receptor, and glucagon-like peptide-1 have recently emerged as neurochemical mediators of LPS anorexia. The central melanocortin system, which is a downstream target of serotonergic neurons, also appears to be involved in mediation of LPS anorexia. Interestingly, LPS also reduce orexin expression and the activity of orexin neurons in the lateral hypothalamic area of fasted mice. As the eating-stimulatory properties of orexin are apparently related to arousal, the inhibitory effect of LPS on orexin neurons might be involved in LPS-induced inactivity and anorexia. In summary, the immune signalling pathways of LPS-induced, and presumably acute illness-induced, anorexia converge on central neural signalling systems that control food intake and energy balance in healthy individuals.

The effect of carbohydrate, protein and fat ingestion on simple as well as complex cognitive functions and the relationship between the respective postprandial metabolic changes and changes in cognitive performance were studied in fifteen healthy male students. Subjects were tested in three sessions, separated by 1 week, for short-term changes in blood variables, indirect calorimetry, subjective performance and different objective performance tasks using a repeated-measures counterbalanced cross-over design. Measurements were made after an overnight fast before and hourly during 3 h after test meal ingestion. Test meals consisted of either pure carbohydrates, protein or fat and were served as isoenergetic (1670 kJ) spoonable creams with similar sensory properties. Most aspects of subjective performance did not differ between test meals. For all objective tasks, however, postprandial cognitive performance was best after fat ingestion concomitant with an almost constant glucose metabolism and constant metabolic activation state measured by glucagon:insulin (G:I). In contrast, carbohydrate as well as protein ingestion resulted in lower overall cognitive performance, both together with partly marked changes (P<0.001) in glucose metabolism and metabolic activation. They also differently affected specific cognitive functions (P<0.05) in relation to their specific effect on metabolism. Carbohydrate ingestion resulted in relatively better short-term memory and accuracy of tasks concomitant with low metabolic activation, whereas protein ingestion resulted in better attention and efficiency of tasks concomitant with higher metabolic activation. Our findings support the concept that good and stable cognitive performance is related to a balanced glucose metabolism and metabolic activation state.