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Biomedical subjects

Michael M Meguid

Publications and source records attributed to Michael M Meguid.

At least 37 records · Page 2Linked to original sources
PubMed2004

Nicotine infusion into rat ventromedial nuclei and effects on monoaminergic system.

Nicotine increases satiety and reduces food intake (FI). We hypothesize that nicotine influences FI via alteration of serotonin (5HT) and dopamine (DA) concentration in ventromedial nucleus (VMN) and lateral hypothalamic area (LHA). Microdialysis cannulas were implanted into ipsilateral VMN and contralateral LHA. Nicotine or vehicle was infused for 60 min into VMN of overnight food-deprived rats, followed by ad lib food for 40 min. Hypothalamic changes in 5HT and DA concentrations were measured every 20 min. Intra-VMN nicotine induced a long-lasting increase in 5HT concentration and an increase in DA for a short duration in the VMN, associated with an increase in 5HT in the LHA. Our data suggest that the nicotine-induced hypophagia correlates with VMN and LHA monoaminergic changes.

Animals↗
PubMed2004

Neurobiologic changes in the hypothalamus associated with weight loss after gastric bypass.

BACKGROUND: Effects of Roux-en-Y gastric bypass (RYGB) on hypothalamic food intake regulation have not been investigated. The hypothalamic arcuate nucleus (ARC) and the magnocellular (m) and parvocellular (p) parts of the paraventricular nucleus (PVN) regulate hunger and satiety, and are under control of the orexigenic neuropeptide Y (NPY), and the anorexigenic alpha-melanocyte stimulating hormone (alpha-MSH) and serotonin (5-HT). We hypothesized that after RYGB, weight loss is associated with hypothalamic down regulation of NPY and up regulation of 5-HT and alpha-MSH. STUDY DESIGN: Obesity was induced in 12 Sprague Dawley rats using a high-energy diet for 7 weeks, and then the rats were divided into three groups (n = 4/group): RYGB, sham-operated pair-fed (PF), and sham-operated ad libitum (obese control). Ten days after operation, immunohistochemical quantification of NPY, alpha-MSH, and 5-HT(1B)-receptors in ARC and PVN was performed. Data were analyzed using ANOVA and Tukey's test. RESULTS: Body weight decreased in RYGB (417 +/- 21 g; mean +/- SE) and in PF (436 +/- 14 g) rats 10 days after operation compared with obese control rats (484 +/- 15 g; p < 0.05 for each comparison). NPY in ARC, pPVN, and mPVN decreased by 43%, 43%, and 61%, respectively in RYGB and by 55%, 42%, and 71% in PF, respectively, compared with obese controls (p < 0.05 for each pairwise comparison). RYGB versus PF did not show differences. alpha-MSH in ARC, pPVN and mPVN increased by 35%, 175%, and 67%, respectively in RYGB and by 29%, 162%, and 116% in PF, respectively, compared with obese controls (each p < 0.05). In mPVN, alpha-MSH significantly decreased by 23% in RYGB versus PF (p < 0.05). 5-HT-(1B)-receptor in pPVN increased by 58% in RYGB and by 26% in PF, compared with obese controls (p < 0.05). Compared with obese controls, 5HT-(1B)-receptor in mPVN increased by 39% in RYGB (p < 0.05) and by 9% in PF (p > 0.05). An increase of 5-HT-(1B)-receptor in pPVN and mPVN occurred in RYGB versus PF (p < 0.05). CONCLUSIONS: Obese rats that undergo weight loss after RYGB demonstrate changes in hypothalamic down regulation of NPY and up regulation of alpha-MSH and serotonin.

Anastomosis, Roux-en-Y↗
PubMed2004

Effects of omega-3 fatty acid supplementation on tumor-bearing rats.

BACKGROUND: Dietary fish oil (rich in omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid) suppresses synthesis and activity of proinflammatory cytokines that induce anorexia. We hypothesized that dietary fish oil reverses the feeding pattern of tumor anorexia, increasing food intake and retarding tumor growth. STUDY DESIGN: Thirty-two Fischer rats were placed in Automated Eater Meter cages and randomly divided into four groups: tumor bearing (TB) rats eating normal chow diet (TB-Chow); TB rats eating chow diet supplemented with omega-3 fatty acids (TB-omega-3FA); Controls, non-tumor bearing (NTB) rats eating normal chow (NTB-Chow); and NTB rats with omega-3 fatty acid supplementation (NTB-omega-3FA). Doses of 10(6) methylcholanthrene (MCA) sarcoma cells were subcutaneously injected in TB rats. Daily food intake, meal size (MZ), meal number (MN), body weight, and tumor volume were measured, and rats were euthanized at onset of anorexia. Data were statistically analyzed using analyses of variance (ANOVA) and t-tests. Data are reported as mean +/- SE. RESULTS: Tumor appeared significantly earlier in TB-Chow than in TB-omega-3FA rats (7.5 +/- 0.3 days versus 11.6 +/- 0.8 days, p < 0.05). Daily food intake declined significantly in TB-Chow versus TB-omega-3FA rats 18 days after tumor inoculation and, at onset of anorexia, was 9.41 +/- 1.77 g/day versus 13.32 +/- 0.81 g/day, p < 0.05. Food intake decreased initially by decrease in meal number (at day 15) followed by a decrease in meal size (at day 18). At onset of anorexia, meal size and meal number were significantly decreased in TB-Chow versus TB-omega-3FA rats (0.75 +/- 0.067 g/meal versus 1.05 +/- 0.08 g/meal, p < 0.05) and (9.5 +/- 1.32 versus 12.79 +/- 0.93 meals/day, p < 0.05), respectively. Tumor volume was significantly smaller in TB-omega-3FA versus TB-Chow rats (7.6 +/- 0.6 cm(3) versus 16.5 +/- 1.0 cm(3), p < 0.05), as was tumor weight (7.5 +/- 2.2 g versus 18.1 +/- 1.6 g, p < 0.05). CONCLUSIONS: In TB rats, omega-3FA improved food intake; restored normal eating pattern, delayed onset of anorexia, tumor appearance, and growth; and prevented body weight loss. Supplementation of omega-3 fatty acids has therapeutic potential in cancer anorexia.

Animals↗
PubMed2004

Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus.

Paraventricular (PVN) concentrations of neuropeptide Y (NPY), serotonin (5-HT) and dopamine (DA) in anorectic tumor-bearing (TB) rats were measured before and after tumor resection. At onset of anorexia in TB versus non-tumor bearing (NTB) Controls 5-HT increased from 12.19+/-0.49 pg/microg to 14.89+/-0.81 pg/microg ( P<0.05 ) while DA and NPY decreased from 7.34+/-0.42 pg/microg to 4.97+/-0.56 pg/microg and 23.47+/-4.27 pg/microg to 13.64+/-1.44 pg/microg, respectively ( P<0.05 ). After tumor resection, these neuromediators normalized when compared to sham-operated NTB rats. NTB pair-fed Controls were also studied. We conclude that the increased 5-HT and the decreased DA and NPY concentrations in PVN are associated with cancer anorexia and that the NPY food stimulatory effect is linked to serotoninergic and dopaminergic systems in hypothalamus.

Animals↗
PubMed2004

Changes in hypothalamic neuropeptide Y and monoaminergic system in tumor-bearing rats: pre- and post-tumor resection and at death.

BACKGROUND: Cancer anorexia is influenced by the neuropeptidergic and monoaminergic systems. We hypothesize that serotonin (5-HT), dopamine (DA) and neuropeptide Y (NPY) concentrations in paraventricular (PVN), ventromedial (VMN), and lateral hypothalamus (LHA) areas are abnormal in tumor-bearing rats. METHODS: Fifty-five Fischer rats (240-280 g) were divided into MCA tumor-bearing (TB), nontumor-bearing (NTB), pair-fed (PF), TB sacrificed at the end of experiment (TB-Terminal), TB resection (TB-Resection), NTB sham-operated (NTB-Sham) and pair-fed sham-operated (PF-Sham) groups. Rats were sacrificed at onset of anorexia (TB, NTB, and PF) and 9 days after tumor resection (TB-Resection, NTB-Sham, PF-Sham, and TB-Terminal). Bilateral PVN, VMN, and LHA were harvested for NPY, 5-HT, and DA analyses. RESULTS: Food intake decreased in TB versus NTB (P < .05). In TB versus NTB, an increase of 5-HT in PVN and VMN occurred with a concomitant decrease in DA. NPY in PVN, VMN, and LHA decreased (P < .05). In TB-Resection versus NTB-Sham, 5-HT, DA, NPY, and FI normalized after tumor resection. CONCLUSIONS: Cancer anorexia is associated with abnormal serotonin, dopamine, and NPY concentrations, expressed by an increase in 5-HT and a decrease in DA and NPY. After tumor resection, these alterations normalized, providing evidence that the levels of these substances change with anorexia in tumor-bearing rats.

Animals↗
PubMed2004

Gene expression profiles post Roux-en-Y gastric bypass.

BACKGROUND: The hypothalamus is involved in regulation of food intake (FI) and fat deposition. Molecular mechanisms of weight loss after Roux-en-Y gastric bypass (RYGB) were studied by correlating changes in gene expression profiles in hypothalamic arcuate nucleus (ARC) and subcutaneous abdominal fat (SAF). METHOD: Diet-induced obese rats were divided into RYGB, sham-operated (SO-Obese), and sham-operated pair-fed (PF) groups. A non-obese group on a regular chow diet served as control. Body weight (BW) and FI were measured. Rats were killed 10 days after the operation. Plasma was analyzed for biochemical indices, ARC and SAF were analyzed for gene expression profiles. Body SAF was also weighed. Data were analyzed by ANOVA and factor analysis. RESULTS: BW and FI decreased in RYGB versus SO-Obese, as reflected by decreased SAF (53%). Genes similarly expressed in ARC and SAF after RYGB were limited to several genes that predominantly related to metabolic pathways of carbohydrate, fat, neuropeptide, and cytokines. These expression profiles were similar to those seen in chow control and to those seen in a comparison of PF and SO-Obese. CONCLUSIONS: RYGB-induced weight loss is associated with changes in gene profile expressions that could influence metabolic changes, contributing to weight loss.

Anastomosis, Roux-en-Y↗
PubMed2004

Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ.

Recent progress in the field of energy homeostasis was triggered by the discovery of adipocyte hormone leptin and revealed a complex regulatory neuroendocrine network. A late addition is the novel stomach hormone ghrelin, which is an endogenous agonist at the growth hormone secretagogne receptor and is the motilin-related family of regulatory peptides. In addition to its ability to stimulate GH secretion and gastric motility, ghrelin stimulates appetite and induces a positive energy balance leading to body weight gain. Leptin and ghrelin are complementary, yet antagonistic, signals reflecting acute and chronic changes in energy balance, the effects of which are mediated by hypothalamic neuropeptides such as neuropeptide Y and agouti-related peptide. Endocrine and vagal afferent pathways are involved in these actions of ghrelin and leptin. Ghrelin is a novel neuroendocrine signal possessing a wide spectrum of biological activities that illustrates the importance of the stomach in providing input into the brain. Defective ghrelin signaling from the stomach could contribute to abnormalities in energy balance, growth, and associated gastrointestinal and neuroendocrine functions.

Aged↗
PubMed2004

Cancer anorexia-cachexia syndrome: cytokines and neuropeptides.

PURPOSE OF REVIEW: Cancer anorexia-cachexia syndrome is observed in 80% of patients in the advanced stages of cancer and is a strong independent risk factor for mortality. Numerous cytokines produced by tumor and immune cells, interacting with the neuropeptidergic system, mediate the cachectic effect of cancer. Since there is currently no effective pharmacological treatment and the anorexia-cachexia syndrome continues to be defined biochemically, we review the role of cytokines and neuropeptides in this process. RECENT FINDINGS: Currently data suggest that cancer anorexia-cachexia syndrome results from a multifactorial process involving many mediators, including hormones (e.g. leptin), neuropeptides (e.g. neuropeptide Y, melanocortin, melanin-concentrating hormone and orexin) and cytokines (e.g. interleukin 1, interleukin 6, tumor necrosis factor alpha and interferon gamma). It is likely that close interrelation among these mediators exists in the hypothalamus, decreasing food intake and leading to cachexia. SUMMARY: In the pathogenesis of cancer anorexia, cytokines play a pivotal role influencing the imbalance of orexigenic and anorexigenic circuits that regulate the homeostatic loop of body-weight regulation, leading to cachexia. Interfering pharmacologically with cytokine expression or neural transduction of cytokine signals can be an effective therapeutic strategy in anorectic patients before they develop cancer anorexia-cachexia syndrome.

Animals↗
PubMed2004

Interleukin-1beta system in anorectic catabolic tumor-bearing rats.

PURPOSE OF REVIEW: The onset of cancer anorexia and the accompanying neurological symptoms and signs involve the general influence of cytokines on the brain. Using methylcholanthrene to induce tumors in Fischer 344 rats, we measured various specific components of the cytokine-induced anorectic reaction, including: (1) IL-1beta system components (ligand, signaling receptor, receptor accessory proteins, and receptor antagonist); (2) TNF-alpha; (3) TGF-beta1; and (4) IFN-gamma in the tumor tissue, the liver and the brain. RECENT FINDINGS: The data show that IL-1beta, TNF-alpha and IFN-gamma messenger RNA were detected in the tumor tissue of anorectic tumor-bearing rats. In brain regions, anorexia is associated with the upregulation of IL-1beta and its receptor mRNA. All other mRNA remained unchanged in the brain regions examined. SUMMARY: This suggests that IL-1beta and its receptor may play a significant role in this model of cancer-associated anorexia. In vivo, the characterization of cytokine components in the brain may provide data for potential pharmacological interventions to ameliorate the anorexia of disease.

Animals↗
PubMed2003

Decreased NPY innervation of the hypothalamic nuclei in rats with cancer anorexia.

Whether the decrease in food intake that occurs at the onset of anorexia in tumor bearing (TB) rats is related to a change in the hypothalamic neuropeptide Y (NPY) system was tested by comparing NPY expression in sham operated Fischer Control and anorectic TB rats. Coronal cryocut sections of their fixed brain were processed by the peroxidase-antiperoxidase method with NPY polyclonal antibodies. NPY-immunoreactive fibers were widely distributed throughout the forebrain, but were most prominent in the hypothalamic paraventricular, suprachiasmatic, arcuate and periventricular nuclei. NPY-immunoreactive neurons were visualized in Control and anorectic TB rats in the preoptic region, the arcuate nucleus, and occasionally in the lateral hypothalamus. Semiquantitative image analysis showed a significant decrease in the NPY immunostaining in some hypothalamic nuclei of the anorectic TB rats, most prominently in the supraoptic nucleus, the parvocellular portion of the paraventricular nucleus, and, to a lesser extent, the suprachiasmatic and arcuate nuclei. No changes in NPY innervation were seen in the ventromedial nucleus and the lateral hypothalamus. The data support the hypothesis of an altered hypothalamic NPY system at the onset of anorexia in TB rats and also reveal the hypothalamic nuclei through which NPY influences food intake.

Animals↗
PubMed2003

Plasma leptin, insulin and free tryptophan contribute to cytokine-induced anorexia.

Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.

Animals↗
PubMed2003

Characterization of the effects of pancreatic polypeptide in the regulation of energy balance.

BACKGROUND & AIMS: Pancreatic polypeptide (PP) belongs to a family of peptides including neuropeptide Y and peptide YY. We examined the role of PP in the regulation of body weight as well as the therapeutic potential of PP. METHODS: We measured food intake, gastric emptying, oxygen consumption, and gene expression of hypothalamic neuropeptides, gastric ghrelin, and adipocytokines in mice after administering PP intraperitoneally. Peptide gene expression was also examined in PP-overexpressing mice. Vagal and sympathetic nerve activities were recorded after intravenous administration in rats. Effects of repeated administrations of PP on energy balance and on glucose and lipid metabolism were examined in both ob/ob obese mice and fatty liver Shionogi (FLS)-ob/ob obese mice. RESULTS: Peripherally administered PP induced negative energy balance by decreasing food intake and gastric emptying while increasing energy expenditure. The mechanism involved modification of expression of feeding-regulatory peptides (decrease in orexigenic neuropeptide Y, orexin, and ghrelin along with an increase in anorexigenic urocortin) and activity of the vagovagal or vagosympathetic reflex arc. PP reduced leptin in white adipose tissue and corticotropin-releasing factor gene expression. The expression of gastric ghrelin and hypothalamic orexin was decreased in PP-overexpressing mice. Repeated administrations of PP decreased body weight gain and ameliorated insulin resistance and hyperlipidemia in both ob/ob obese mice and FLS-ob/ob obese mice. Liver enzyme abnormalities in FLS-ob/ob obese mice were also ameliorated by PP. CONCLUSIONS: These observations indicate that PP may influence food intake, energy metabolism, and the expression of hypothalamic peptides and gastric ghrelin.

Animals↗
PubMed2003

Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies.

Anorexia and reduced food intake are important issues in the management of patients with cancer because they contribute to the development of malnutrition, increase morbidity and mortality, and impinge on quality of life. Accumulating evidence indicates that cancer anorexia is multifactorial in its pathogenesis, and most of the hypothalamic neuronal signalling pathways modulating energy intake are likely to be involved. Several factors are considered to be putative mediators of cancer anorexia, including hormones (eg, leptin), neuropeptides (eg, neuropeptide Y), cytokines (eg, interleukin 1 and 6, and tumour necrosis factor), and neurotransmitters (eg, serotonin and dopamine). These pathways are not isolated and distinct pathogenic mechanisms but are closely inter-related. However, convincing evidence suggests that cytokines have a vital role, triggering the complex neurochemical cascade which leads to the onset of cancer anorexia. Increased expression of cytokines during tumour growth prevents the hypothalamus from responding appropriately to peripheral signals, by persistently activating anorexigenic systems and inhibiting prophagic pathways. Hypothalamic monoaminergic neurotransmission may contribute to these effects. Thus, the optimum therapeutic approach to anorectic cancer patients should include changes in dietary habits, achieved via nutritional counselling, and drug therapy, aimed at interfering with cytokine expression or hypothalamic monoaminergic neurotransmission.

Anorexia↗
PubMed2003

Is obesity an inflammatory disease?

BACKGROUND: Most obese individuals have elevated concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), markers of inflammation closely associated with diabetes, hypertension, and stroke. HYPOTHESIS: Obesity is a low-grade inflammatory disease, and Roux-en-Y gastric bypass (RYGB) reduces biochemical markers of inflammation and modifies gene expression in hypothalamic food intake/energy-related nuclei and subcutaneous abdominal fat (SAF). METHODS: Obesity was induced in 24 3-week-old Sprague Dawley pups fed a high-energy diet (HED). Three groups (n = 8/group) were studied: RYGB, sham-operated pair-fed, and sham-operated ad libitum HED. Controls were nonobese rats fed chow (n = 6). Rats were killed 10 days after operation, and blood was collected to measure corticosterone and SAF and mesenteric fat to measure IL-6, TNF-alpha, and corticosterone. Total mRNA from arcuate nucleus and SAF purified for gene expression profiling. Data were analyzed with analysis of variance, Mann-Whitney test, and t test. RESULTS: Before operation, the body weight of the obese groups was 493 +/- 7 g and control = 394 +/- 12g. The 10-day postoperative weight was RYGB = 417 +/- 21 g, pair-fed = 436 +/- 14 g, and ad libitum HED = 484 +/- 15 g. Mesenteric and SAF weight decreased in RYGB. Mesenteric/SAF ratio of IL-6, TNF-alpha, corticosterone, and gene profiling showed decrease of inflammation after RYGB. CONCLUSIONS: Gastric bypass reduces biochemical markers of inflammation, suggesting that obesity is an inflammatory condition.

Adipose Tissue↗
PubMed2003

Metabolic alterations during inflammation and its modulation by central actions of omega-3 fatty acids.

PURPOSE OF REVIEW: To discuss the possible relationship between long-chain polyunsaturated fatty acids, cytokines, anandamides, nitric oxide, leptin, various neurotransmitters in the brain, and their role in anorexia of acute and chronic inflammatory conditions and cancer. RECENT FINDINGS: Recent studies have shown that long-chain polyunsaturated fatty acids, especially the omega-3 series, have antiinflammatory actions, increase the concentrations of anandamides, enhance the levels of acetylcholine and nitric oxide and modulate the concentrations and actions of various neurotransmitters, including leptin, in the brain. Patients suffering from acute and chronic inflammatory conditions have low tissue concentrations of various long-chain polyunsaturated fatty acids, and high levels of proinflammatory cytokines that can cause anorexia and decrease food intake. SUMMARY: It is suggested that supplementation of long-chain polyunsaturated fatty acids may have a role in the prevention and treatment of acute and chronic inflammatory conditions, improving anorexia associated with these conditions.

Animals↗