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 Between lunch and dinner, blood was withdrawn continuously and collected every 10min for measures of plasma concentrations of glucose, insulin, lactate, TAG, NEFA, β-hydroxybutyrate (BHB), leptin and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

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

Effect of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats

OBJECTIVE: Deficiencies of vitamin A and iodine are common in many developing countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism. The study aim was to investigate the effects of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats. DESIGN: Weanling rats (n = 56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin A and iodine (VAD + ID group), or sufficient in both vitamin A and iodine (control) for 30 days in a pair-fed design. Serum retinol (SR), thyroid hormones (FT(4), TT(4), FT(3), and TT(3)), serum thyrotropin (TSH), pituitary TSHbeta mRNA expression levels, and thyroid weights were determined at the end of the depletion period. MAIN OUTCOME: Compared to the control and ID groups, SR concentrations were about 35% lower in the VAD and VAD + ID groups (p < 0.001), indicating moderate VA deficiency. Comparing the VAD and control groups, there were no significant differences in TSH, TSHbeta mRNA, thyroid weight, or thyroid hormone levels. Compared to the control group, serum TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.05), and FT4 and TT4 were lower (p < 0.001), in the VAD + ID and ID groups. Compared to the ID group, TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.01) and FT(4) and TT(4) were lower (p < 0.001) in the VAD + ID group. There were no significant differences in TT3 or FT3 concentrations among groups. CONCLUSION: Moderate VAD alone has no measurable effect on the pituitary-thyroid axis. Concurrent ID and VAD produce more severe primary hypothyroidism than ID alone

The L cell transcriptome is unaffected by vertical sleeve gastrectomy but highly dependent upon position within the gastrointestinal tract

Altered GLP-1 secretion from L cells has been implicated in the development of type 2 diabetes mellitus and its resolution following bariatric surgery. However, changes in L cell gene expression, which may form the basis for altered functionality after high fat diet (HFD) or bariatric surgery, have either not been investigated or have given conflicting results. We developed a gcg-DTR-eGFP reporter mouse to isolate ileal and colonic L cells from HFD fed insulin resistant mice and mice showing improved glucose tolerance following vertical sleeve gastrectomy (VSG). Transcriptomic sequencing and identification of genes differentially expressed in response to HFD or VSG revealed small changes with HFD, primarily in immune related genes, but no regulation following VSG. In contrast, large differences were observed between ileal and colonic L cells due to the differential expression of genes involved in nutrient transport and metabolism, reflecting to some extent the differences in the surrounding epithelium. We showed that, in line with the gene expression data, colonic and ileal L cells exhibit differing GLP-1 responses to nutrients (glucose and the gly-sar dipeptide) and hormones (vasopressin). Thus, we hypothesise that colonic and ileal L cells have different physiological roles, with ileal L cells contributing more to postprandial glucose homeostasis by responding to dietary nutrients and colonic cells responding more to non-dietary stimulants

Cognitive effects of subdiaphragmatic vagal deafferentation in rats

Vagal afferents are a crucial neuronal component of the gut-brain axis and mediate the information flow from the viscera to the central nervous system. Based on the findings provided by experiments involving vagus nerve stimulation, it has been suggested that vagal afferent signaling may influence various cognitive functions such as recognition memory and cognitive flexibility. Here, we examined this hypothesis using a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective abdominal vagal deafferentation method existing to date. We found that SDA did not affect working memory in a nonspatial alternation task, nor did it influence short-, intermediate-, and long-term object recognition memory. SDA did also not affect the acquisition of positively reinforced left-right discrimination learning, but it facilitated the subsequent reversal left-right discrimination learning. The SDA-induced effects on reversal learning emerged in the absence of concomitant changes in motivation towards the positive reinforcer, indicating selective effects on cognitive flexibility. Taken together, these findings suggest that the relative contribution of vagal afferent signaling to cognitive functions is limited. At the same time, our study demonstrates that cognitive flexibility, at least in the domains of positively reinforced learning, is subjected to visceral modulation through abdominal vagal afferents

Menopause is associated with decreased postprandial ghrelin, while a history of anorexia nervosa is associated with increased total ghrelin

INTRODUCTION: Middle age has been linked with various dysfunctional eating patterns in women. The hormone ghrelin is related to food intake, with plasma levels rising before eating and decreasing immediately afterwards. Animal research has shown that estradiol is an antagonist of ghrelin. Given that both menopause and anorexia nervosa (AN) are states characterised by reduced estradiol, the goal of the present study was to investigate for the first time whether menopausal status and a history of AN are linked with altered ghrelin levels in middle-aged women. Based on previous research, we hypothesised that a) post-menopausal women would demonstrate comparably increased ghrelin after food intake and b) women with a history of AN would exhibit increased total ghrelin levels. METHODS: Healthy, middle-aged women (N=57) were recruited. N=31 were post-menopausal and n=27 had a history of AN. Plasma was repeatedly collected before and after a meal standardised in terms of caloric content. Areas under the curves were calculated to indicate total (AUCg) and postprandial ghrelin (AUCi). RESULTS: Menopausal status was linked with postprandial ghrelin (AUCi -1.6±2.2 vs. -2.9±2.6; p=.058), while a history of AN was linked with total ghrelin (AUCg 36.2±5.6 vs. 39.0±3.7; p=.050). There were no interaction effects (both p>.466). A closer examination of the effects revealed that post-menopausal women showed marginally greater decreases in ghrelin immediately after food intake (p=.064) and marginally greater re-increases after 60 min (p=.084) when compared to pre-menopausal women. Women with a history of AN had significantly higher total ghrelin when compared to women without a history of AN (p=.042). DISCUSSION: Post-menopause was linked with higher sensitivity of ghrelin to food intake (trend), while a history of AN was related to greater total ghrelin. Future research should investigate to what extent the observed alterations in ghrelin may affect dysfunctional eating behaviour during middle age

Abdominal vagal deafferentation alters affective behaviors in rats

Background: There is growing evidence for a role of abnormal gut-brain signaling in disorders involving altered mood and affect, including depression. Studies using vagus nerve stimulation (VNS) suggest that the disruption of vagal afferent signaling may contribute to these abnormalities. To test this hypothesis, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on affective behaviors. Methods: SDA- and Sham-operated male rats were subjected to several tests that are commonly used in preclinical rodent models to assess the presence of anhedonic behavior, namely the novel object-induced exploration test, the novelty-suppressed eating test, and the sucrose preference test. In addition, we compared SDA and Sham rats in a social interaction test and the forced swim test to assess sociability and behavioral despair, respectively. Results: Compared to Sham controls, SDA rats consistently displayed signs of anhedonic behavior in all test settings used. SDA rats also showed increased immobility and reduced swimming in the forced swim test, whereas they did not differ from Sham controls with regards to social approach behavior. Limitations: This study was conducted in male rats only. Hence, possible sex-specific effects of SDA on affective behaviors remained unexamined. Conclusions: Our findings demonstrate that hedonic behavior and behavioral despair are subject to visceral modulation through abdominal vagal afferents. These data are compatible with preclinical models and clinical trials showing beneficial effects of VNS on depression-like and affective behaviors

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

ISSN:0007-1145ISSN:1475-266