Signals generating anorexia during acute illness: Symposium on ‘Eating, illness and the gut: is there disorder in the house?'

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 individual

Tanniferous forage plants with anthelmintic properties: the example of sainfoin (Onobrychis viciifolia)

Introduction: Sainfoin is a high-quality condensed tannin containing forage plant. The knowledge about anthelmintic effects against sheep nematodes and about the influence of plant preservation (e.g. ensiling) on the anthelmintic activity is limited. Method: 36 parasite naïve lambs (6 groups of 6 animals each) were infected with H. contortus (7,000 L3) and C. curticei (15,000 L3). From day 28 until day 44 p.i., groups A1, B1 and C1 received fresh, dried or ensiled sainfoin. Groups A2, B2 and C2 served as respective tannin-free controls. Individual faecal egg counts on a dry matter basis (FECDM) were performed every 3-4 days. On day 44, all animals were slaughtered and adult worm populations were determined. Results: The consumption of sainfoin was associated with a reduction of adult H. contortus (35% (P<0.1), 47% (P<0.05) and 49% (P<0.1) for fresh, dried and ensiled sainfoin, respectively) but had little effect on adult C. curticei. Compared to the controls, H. contortus specific FECDM was reduced by 62% (P<0.05), 58% (P<0.01) and 48% (P<0.1) for fresh, dried and ensiled sainfoin. FECDM specific to C. curticei were decreased by sainfoin hay and silage (hay 81% , silage 74%, both tests P<0.001) but were unchanged when fresh sainfoin was administered. Conclusion: For H. contortus the FECDM decrease seemed to be due to a nematocidal effect towards adult H. contortus. In contrast for C. curticei, the reduction in FECDM appeared to be a result of a reduced per capita fecundity. The use of conserved tanniferous fodder offers promising perspectives as a complementary control approach against nematodes in sheep

Effect of sainfoin (Onobrychis viciifolia) silage and hay against gastrointestinal nematodes in lambs

The objective of the study was to examine the effect of dried and ensiled sainfoin (Onobrychis viciifolia) against two species of gastrointestinal nematodes (Haemonchus contortus, Cooperia curticei) in lambs. Twenty-four days post experimental infection, 24 lambs were allocated to 4 equal groups. Group A and B received sainfoin silage and control silage respectively for 16 days. Groups C and D were fed on sainfoin hay or control hay for the same period. Feeds were administered ad libitum and mean refusals and live weight were regularly recorded. Individual faecal egg counts (FEC) were performed twice weekly. After the feeding period all lambs were slaughtered for post mortem investigation. The consumption of sainfoin hay was associated with a significant reduction of the adult H. contortus burden by 47 % (P < 0.05) whereas no significant difference was seen when feeding sainfoin silage (49 %, P = 0.112). The C. curticei worm burden was not significantly reduced by either sainfoin hay or silage. At slaughter FEC were significantly reduced by sainfoin hay by 64 % (P < 0.001) compared to the control feed. After feeding sainfoin silage FEC decreased by 48 % (P = 0.056). There was a tendency of better live weight gain in sainfoin hay fed animals compared to the control fed ones (P=0.07). These results demonstrate a nematocidal effect of a tanniferous forage legume against gastrointestinal nema¬¬todes, which was more pronounced against H. contortus. The antiparasitic effects were largely preserved when feeding sainfoin silage, suggesting this conservation procedure to be a valuable alternative to hay

Differential Circadian Eating Patterns in Two Psychogenetically Selected Strains of Rats Fed Low-, Medium-, and High-Fat Diets

Spontaneous eating patterns in male, inbred Roman high- and low-avoidance rats (RHA/Verh, RLA/Verh) were continuously recorded while animals were successively offered three isocaloric (≍16.5-kJ/g) diets: a low-fat, high-carbohydrate diet (LF; 3.3% fat), a medium-fat diet (MF; 18% fat), and a high-fat diet (HF; 40% fat), the latter being followed once again by the LF diet. Under the conditions of this experiment, overall 24h food intake did not differ significantly between RHA/Verh and RLA/Verh rats, but was significantly higher for both rat strains on the MF and HF diets than on the LF diet. Despite the similar 24h-food intake, RHA/Verh rats ate transiently less than RLA/Verh rats during the third quarter of the dark phase under all dietary conditions. These differences were due to the RHA/Verh rats' longer intermeal intervals (with all diets) and smaller meals (with the MF and HF diets) and were compensated for during the last 3 h of the dark phase. On the LF diet, dark-phase meal frequency was higher and both nocturnal meal size and mean eating rate within meals were lower in RLA/Verh rats than in RHA/Verh rats. With the MF and HF diets, mean nocturnal meal size and meal duration were higher and mean eating rate was lower in RLA/Verh rats than in RHA/Verh rats. For both strains, nocturnal meal size was significantly higher with the MF and HF diets than with the LF diet, and nocturnal meal frequency was lower with the HF diet than with the other two diets. Although body weights were similar at the start of the study, RLA/Verh rats gained significantly more weight than did RHA/Verh rats by the end. As has often been the case with other aspects of behavior studied, differences in neuromodulatory systems (e.g., serotoninergic and dopaminergic) between RHA/Verh and RLA/Verh rats may directly or indirectly contribute to the subtle differences in eating patterns observed her

Cognitive performance and its relationship with postprandial metabolic changes after ingestion of different macronutrients in the morning

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 stat

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats

Both ovariectomy in rats and menopause are associated with increased TAT. After ovariectomy, fat is preferentially deposited as SAT and lean body mass increases, whereas after menopause fat is preferentially deposited as IAAT and lean body mass decreases. These opposite effects of ovariectomy and menopause on regional AT distribution and lean body mass indicate that ovariectomy in rats is not a homologous model of menopause-associated changes in body composition that should be used with great caution in investigations of adiposity-related diseases

Acute effects of pharmacological modifications of fatty acid metabolism on human satiety

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 (320mg), HCA (2g) or placebo (PLA) in random order. Between lunch and dinner, blood was withdrawn continuously and collected every 10min 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 210min 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 oxidatio

Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

To determine whether Toxoplasma gondii infection could modify biological phenomena associated with brain ischemia, we investigated the effect of permanent middle cerebral artery occlusion (MCAO) on neuronal survival, inflammation and redox state in chronically infected mice. Infected animals showed a 40% to 50% decrease of infarct size compared with non-infected littermates 1, 4 and 14 days after MCAO. The resistance of infected mice may be associated with increased basal levels of anti-inflammatory cytokines and/or a marked reduction of the MCAO-related brain induction of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma (IFNγ). In addition, potential anti-inflammatory/neuroprotective factors such as nerve growth factor, suppressor of cytokine signaling-3, superoxide dismutase activity, uncoupling protein-2 and glutathione (GSH) were upregulated in the brain of infected mice. Consistent with a role of GSH in central cytokine regulation, GSH depletion by diethyl maleate inhibited Toxoplasma gondii lesion resistance by increasing the proinflammatory cytokine IFNγ brain levels. Overall, these findings indicate that chronic toxoplasmosis decisively influences both the inflammatory molecular events and outcome of cerebral ischemia

A Rat Model of Human Lipid Emulsion Digestion

A better understanding of how dietary lipids are processed by the human body is necessary to allow for the control of satiation and energy intake by tailored lipid systems. To examine whether rats are a valid model of human dietary lipid processing and therefore useful for further mechanistic studies in this context, we tested in rats three lipid emulsions of different stability, which alter satiety responses in humans. Different sets of 15 adult male Sprague Dawley rats, equipped with gastric catheters alone or combined with hepatic portal vein (HPV) and vena cava (VC) catheters were maintained on a medium-fat diet and adapted to an 8 h deprivation/16 h feeding schedule. Experiments were performed in a randomized cross-over study design. After gastric infusion of the lipid emulsions, we assessed gastric emptying by the paracetamol absorption test and recorded in separate experiments food intake and plasma levels of gastrointestinal hormones and metabolites in the HPV. For an acid stable emulsion, slower gastric emptying and an enhanced release of satiating gastrointestinal (GI) hormones were observed and were associated with lower short-term energy intake in rats and less hunger in humans, respectively. The magnitude of hormonal responses was related to the acid stability and redispersibility of the emulsions and thus seems to depend on the availability of lipids for digestion. Plasma metabolite levels were unaffected by the emulsion induced changes in lipolysis. The results support that structured lipid systems are digested similarly in rats and humans. Thus unstable emulsions undergo the same intragastric destabilization in both species, i.e., increased droplet size and creaming. This work establishes the rat as a viable animal model for in vivo studies on the control of satiation and energy intake by tailored lipid systems