Role In Control Of Food Intake Research Articles

Effects of age on feeding response: Focus on the rostral C1 neuron and its glucoregulatory proteins.

Older people are likely to develop anorexia of aging. Rostral C1 (rC1) catecholaminergic neurons in rostral ventrolateral medulla (RVLM) are recently discovered its role in food intake control. It is well established that these neurons regulate cardiovascular function. This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response. Male Sprague Dawley rats at 3-months (n = 22) and 24-months (n = 22) old were used and further divided into two subgroups; 1) treatment group with 2-deoxy-d-glucose (2DG) and 2) vehicle group. Feeding hormones such as cholecystokinin (CCK), ghrelin and leptin were analysed using enzyme-linked immunosorbent assay (ELISA). Rat brain was carefully dissected to obtain the brainstem RVLM region. Further analysis was carried out to determine the level of proteins and genes in RVLM that were associated with feeding pathway. Protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK) and neuropeptide Y Y5 receptor (NPY5R) were determined by western blot. Expression of TH, AMPK and NPY genes were determined by real-time PCR. This study showed that blood glucose level was elevated in young and old rats following 2DG administration. Plasma CCK-8 concentration was higher in the aged rats at basal and increased with 2DG administration in young rats, but the leptin and ghrelin showed no changes. Old rats showed higher TH and lower AMPK mRNA levels. Glucoprivation decreased AMPK mRNA level in young rats and decreased TH mRNA in old rats. Aged rC1 neurons showed higher NPY5R protein level. Following glucoprivation, rC1 neurons produced distinct molecular changes across age in which, in young rats, AMPK phosphorylation level was increased and in old rats, TH phosphorylation level was increased. These findings suggest that glucose-counterregulatory responses by rC1 neurons at least, contribute to the ability of young and old rats in coping glucoprivation. Age-induced molecular changes within rC1 neurons may attenuate the glucoprivic responses. This situation may explain the impairment of feeding response in the elderly.

Cafeteria diet induces progressive changes in hypothalamic mechanisms involved in food intake control at different feeding periods in female rats

We studied the effects of cafeteria diet (CAF) intake from weaning on mRNA levels and DNA methylation state of feeding-related neuropeptides and hormone receptors in individual hypothalamic nuclei at different feeding periods. Four weeks of CAF (short-term) increased energy intake and adiposity, without affecting neuropeptides’ expression. Eleven weeks of CAF (medium-term) increased energy intake, adiposity, leptinemia, and body weight, with an orexigenic response of the lateral hypothalamus, paraventricular and ventromedial nuclei, given by upregulation of Orexins, AgRP, and NPY opposed by an anorectic signal of the arcuate nucleus, which displayed a higher POMC expression. The changes in neuropeptidic mRNA levels were related to epigenetic modifications in their promoter regions. Metabolic and molecular changes were intensified after 20 weeks of diet (long-term). The alterations in these hypothalamic brain nuclei could add information about their differential role in food intake control, and how their action is disrupted during the development of obesity.

A short-term dynamical model for ghrelin

Ghrelin, a peptide hormone, occupies a crucial role in food intake control. Differently from other hormones contributing to energy homeostasis, usually exerting their regulating action by signaling satiety (e.g. leptin), ghrelin is known to stimulate appetite and, in general, to upsurge the propensity of animals to seek out food and start eating. Medical and experimental literature has shown that approximately 70-80% of ghrelin production occurs in the stomach, whilst the great part of ghrelin control, leading to ghrelin suppression soon after a meal administration, is exerted by signals originated in the small intestine. This note proposes a mathematical model for ghrelin dynamics, focusing the attention on its short-term 24 hours dynamics. The proposed model conforms to the established physiology by introducing a minimal multi-compartmental structure of the gastrointestinal tract. Model parameters are set in order to fit plasma ghrelin concentration data taken from the literature, related to an experiment in humans: simulation-based ghrelin predictions provide promising results if compared to real data. Besides to offer a proper description of the short-term ghrelin dynamics, the model can be thought of as a module of a bigger multi-compartmental structure, aiming to account for the “web of hormones” (including, e.g., leptin and insulin) related to food intake and energy homeostasis.

Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei

We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity.

Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake.

Central glucagon-like peptide 1 receptor (GLP-1R) stimulation suppresses food intake, and hindbrain GLP-1 neurons project to numerous feeding-relevant brain regions. One such region is the nucleus accumbens (NAc), which plays a role in reward and motivated behavior. Using immunohistochemical and retrograde tracing techniques in rats, we identified a robust projection from GLP-1 neurons in the nucleus of the solitary tract to the NAc. We hypothesized that activation of NAc GLP-1Rs suppresses feeding. When injected into the NAc core of rats at doses subthreshold for effect when administered to the lateral ventricle, GLP-1 significantly reduced food intake relative to vehicle at 1, 2, and 24 h posttreatment. The same doses had no effect when injected into the NAc shell. NAc core treatment with ventricle-subthreshold doses of the GLP-1R antagonist exendin (9-39) caused significant hyperphagia at 2 h posttreatment, suggesting that endogenous stimulation of NAc core GLP-1Rs plays a role in limiting food intake. It has been suggested that GLP-1 can cause nausea, but we found that NAc core administration of GLP-1 did not cause a conditioned taste aversion to saccharin, suggesting that the anorexic effect of NAc core GLP-1 is not caused by malaise. Finally, we observed that NAc core injection of GLP-1 significantly increased c-Fos expression in the NAc core. We conclude that that GLP-1Rs in the NAc play a physiologic role in food intake control, and suggest that the GLP-1 projection to NAc core may link satiation signal processing in the hindbrain with forebrain processing of food reward.

Ghrelin effects on central glucosensing and energy homeostasis-related peptides in rainbow trout

Although the role of ghrelin (GHRL) on fish appetite regulation had been widely studied in past years, its involvement in the regulation of glucose metabolism had been little explored. In the present study we hypothesize that GHRL may have a role in the regulation of glucose homeostasis in fish. Therefore, we carried out different experimental approaches in rainbow trout to assess brain glucosensing potential and glucose metabolism in response to GHRL treatment. We found that after either systemic or central GHRL administration to trout deprived of food, glycemia remained unaffected, whereas (in clear contrast with the mammalian model) a consistent activation of the main glucosensing markers (glucose transporter 2, glucokinase, and ATP-sensitive inward rectified K + channel) was noticed in both hypothalamus and hindbrain. Some of these results were further confirmed by in vitro incubations of hypothalamus and hindbrain in the presence of GHRL. Despite the lack of changes in glycemia, we suggest that the changes elicited by GHRL on the glucosensing system are direct and could be related to a helper action of this hormone when glucose arrived in the postprandial phase. Moreover, we also studied the effect of GHRL treatment on the expression of several food intake-related neuropeptides, such as neuropeptide Y, cocaine- and amphetamine-regulated transcript, pro-opiomelanocortin, and corticotropin-releasing factor. We observed an important variability in the effects of GHRL attributable either to the route of GHRL administration or to the brain regions assessed, which could help explain the contradictory results described in fish literature about GHRL role in food intake control.

Leptin inhibits norepinephrine and dopamine release from rat hypothalamic neuronal endings

Noradrenergic and dopaminergic afferents arising from the brain stem to the hypothalamus still play a poorly characterised role in food intake control. We have studied the effect of leptin, an adipocyte-derived hormone which has been implicated in the regulation of feeding behaviour, on [ 3 H ]norepinephrine and [ 3 H ]dopamine release from perfused hypothalamic neuronal endings (synaptosomes) in vitro. We have found that leptin (0.01–10 nM) does not modify basal, while it inhibits depolarization-induced norepinephrine and dopamine release. We can hypothesize that at least part of the anorectic activity of leptin in the hypothalamus is effected through an inhibition of noradrenergic and dopaminergic firing.

Peripheral Regulation of Food Intake in Poultry

This review focuses on food intake regulation in avian species with the emphasis on sites of action outside of the central nervous system using data obtained mainly with studies involving poultry. Avian species do appear to regulate food intake, and there is good evidence that both the gastrointestinal tract and the liver are primary sites for regulation. Although young meat-type chickens may be eating near gut capacity, this does not appear to be the case in older birds. Furthermore, although the crop probably has a role in food intake control when meal feeding, its role during free access feeding is marginal. Food intake can be altered in chickens by infusion of glucose, lipids, epinephrine and possibly amino acids into the liver. The response to such infusions is altered by genotype and feeding state (fed or unfed). In addition, injection of peptides including cholecystokinin, bombesin, and gastrin outside the central nervous system decrease food intake. It is uncertain whether the anorexigenic effect of these peptides is a specific response, or if it is a general response caused by abdominal discomfort. Opioids appear to stimulate food intake with at least part of their effect being from outside of the central nervous system. Therefore, although the central nervous system is involved in food intake control in avian species, there are other sites involved. Furthermore, genetic selection for growth in meat-type chickens has altered the responsiveness of these control mechanisms suggesting that there is genetic variation for these physiological systems.

Cerebral and hepatic glucoreceptors: Assessment of their role in food intake control by the uptake of 3H-2deoxy-D-glucose

The relative contributions of cerebral and hepatic glucoreceptors in the regulation of food intake is estimated on the basis of the distribution of the labelled glucose antimetabolite — 3H-2DG — in selected glucosensitive tissues under conditions in which the non-radioactive 2DG was previously shown to be a highly effective stimulus for the initiation of food intake.