Effects of Irregular Feeding on the Daily Fluctuations in mRNA Expression of the Neurosecretory Protein GL and Neurosecretory Protein GM Genes in the Mouse Hypothalamus.

Circadian desynchrony induced by a long period of irregular feeding leads to metabolic diseases, such as obesity and diabetes mellitus. The recently identified neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are hypothalamic small proteins that stimulate food intake and fat accumulation in several animals. To clarify the mechanisms that evoke feeding behavior and induce energy metabolism at the appropriate times in accordance with a circadian rhythm, diurnal fluctuations in Npgl and Npgm mRNA expression were investigated in mice. Quantitative RT-PCR analysis revealed that the mRNAs of these two genes were highly expressed in the mediobasal hypothalamus during the active dark phase under ad libitum feeding. In mice restricted to 3 h of feeding during the inactive light phase, the Npgl mRNA level was augmented in the moment prior to the feeding period and the midnight peak of Npgm mRNA was attenuated. Moreover, the mRNA expression levels of clock genes, feeding regulatory neuropeptides, and lipid metabolic enzymes in the central and peripheral tissues were comparable to those of central Npgl and Npgm. These data suggest that Npgl and Npgm transcription fluctuates daily and likely mediates feeding behavior and/or energy metabolism at an appropriate time according to the meal timing.

Protective Effect of D-Methionine on Body Weight Loss, Anorexia, and Nephrotoxicity in Cisplatin-Induced Chronic Toxicity in Rats.

D-methionine is a sulfur-containing amino acid that can act as a potent antioxidant. Anorexia and nephrotoxicity are side effects of cisplatin. The protective effects of D-methionine on cisplatin-induced anorexia and renal injury were investigated. The model of chronic cisplatin administration (5 mg/kg body weight) involved intraperitoneal injection on days 1, 8, and 15 and oral D-methionine (300 mg/kg body weight) coadministration daily for 20 days. On the 21st day of treatment, food intake and body weight in the cisplatin-treated group significantly decreased by 52% and 31%, respectively, when compared with a control group. D-methionine coadministration with cisplatin decreased food intake and body weight by 29% and 8%, respectively. In cisplatin-treated rats, white blood cell, mean corpuscular volume, and platelet values significantly decreased, while mean corpuscular hemoglobin concentration significantly increased by 8.6% when compared with control rats. Cisplatin administration resulted in significantly decreased feeding efficiency, elevated renal oxidative stress, and reduced antioxidative activity. Leukocyte infiltration, tubule vacuolization, tubular expansion, and swelling were observed in the kidneys of cisplatin-treated rats. Oral D-methionine exhibited an antianorexic effect, with improvement in food intake, feeding efficiency, and hematological toxicities, as well as a protective effect against nephrotoxicity by elevated antioxidative activity. D-methionine may serve as a chemoprotectant in patients receiving cisplatin as part of a chemotherapy regimen.

Hypothalamic pathways regulate the anorectic action of p-chloro-diphenyl diselenide in rats.

Behavioral studies have suggested that (p-ClPhSe)2 elicits an anorectic-like action in rats by inducing multiple effects such as satiety-enhancing effect, malaise and specific flavor; however, the molecular mechanisms underlying its anorexigenic action remain unclarified. Here, male Sprague-Dawley rats received acute and sub-chronic intraperitoneal treatments with (p-ClPhSe)2; thereafter, in vivo and ex vivo analyses were carried out. The present study reveals that the reduction of food intake resulting from a single treatment with (p-ClPhSe)2 (1mg/kg, i.p.) was associated with decreased hypothalamic levels of pro-melanin-concentrating hormone (pro-MCH) and orexin precursor. In addition, repeated administrations of (p-ClPhSe)2 (10mg/kg; i.p.) for 7 days induced sustained food intake suppression, body weight loss and white fat reduction. Measurements of brown adipose tissue content and temperature as well as data obtained from a pair-fed group indicated that the effects of (p-ClPhSe)2 on the body weight are closely related to its anorexigenic actions, ruling out the possibility of increased thermogenesis. Furthermore, (p-ClPhSe)2 reduced the hypothalamic orexin precursor levels when repeatedly administered to rats. Sub-chronic treatment with (p-ClPhSe)2 caused a decrease of serum triglyceride levels and down-regulation of hepatic cholesterol content. Therefore, the current study characterized the anorectic and reducing body weight actions of (p-ClPhSe)2 in Sprague-Dawley rats. Besides, the set of results suggests that food intake suppressant effects triggered after (p-ClPhSe)2 administration to rats are mainly related with the lower orexin levels in hypothalamus after acute and sub-chronic treatments.

Cancer anorexia: hypothalamic activity and its association with inflammation and appetite-regulating peptides in lung cancer.

BACKGROUND: Energy homeostasis is mediated by the hypothalamus, whose inflammation-induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non-anorexic (NA) cancer patients, and in controls (C). METHODS: Lung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used. RESULTS: Thirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all-time points, anorexic patients showed lower hypothalamic activity compared with NA (P < 0.001) (T0: 585.57 ± 55.69 vs. 667.92 ± 33.18, respectively; T1: 536.50 ± 61.70 vs. 624.49 ± 55.51, respectively; T2: 556.44 ± 58.51 vs. 615.43 ± 71.50, respectively). Anorexic patients showed greater BOLD signal reduction during T0-T1 than NA (-8.5% vs. -6.80%, P < 0.001). Independently from the presence of anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL-1 and ghrelin (P < 0.001). CONCLUSIONS: Hypothalamic activity in A cancer patients is reduced respect to NA and responds differently to oral challenges. This suggests a central control of appetite dysregulation during cancer anorexia, before, and after oral intake.

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation.

OBJECTIVE: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. METHODS: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. RESULTS: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. CONCLUSIONS: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained 'perpetual cycle' of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity.

Orally administered δ opioid agonist peptide rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.

SCOPE: It is known that a decline in food intake occurs with aging. In this study, we investigated changes in parameters associated with food intake in response to aging, and whether orexigenic peptides stimulated food intake after peripheral administration even in aged mice. METHODS AND RESULTS: Food intake and body weight of 27-month-old male C57BL/6N mice were lower than those of 15-month-old mice. Epididymal and mesenteric fat mass, blood glucose, triglyceride, and leptin levels were also decreased. Meanwhile, the hypothalamic mRNA expression of endogenous orexigenic peptides such as neuropeptide Y (NPY) and agouti-related protein, also called agouti-related peptide, was increased. Next, we tested responsiveness to exogenously administered orexigenic peptides coupled to NPY in aged as well as young mice. Orally administered rubiscolin-6, a δ opioid agonist hexapeptide derived from a major green leaf protein Rubisco, stimulated food intake in 27-month-old mice. In contrast, ghrelin was ineffective after intraperitoneal administration to aged mice, suggesting that the NPY system downstream of ghrelin but not δ opioid receptors might be impaired in aged mice. CONCLUSION: Orally administered rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats.

PURPOSE: Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits. METHODS: The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet. RESULTS: Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses. CONCLUSION: Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.

[Impacts on the appetite regulating factors of infantile anorexia treated with acupuncture at Sifeng (EX-UE 10)].

OBJECTIVE: To explore the dynamic change and clinical efficacy of acupuncture at Sifeng (EX-UE 10) on appetite regulating factors in the serum of infantile anorexia. METHODS: Eighty cases, in compliance with the diagnostic criteria, aged from 3 to 6 years were randomized into an acupuncture group and a medication group, 40 cases in each one. Additionally, a healthy control group (30 cases) was set up. In the acupuncture group, the pricking method was adopted at Sifeng (EX-UE 10) with the three-edged needle. A few light yellow, transparent viscous liquid or blood was squeezed out after pricking. The treatment was given once a week, for 4 weeks totally. In the medication group, erkangning syrup was administered, 3 times a day, for 4 weeks totally. The ghrelin, leptin and neuropeptide Y (NPY), and the clinical efficacy were observed before and after treatment in each group. RESULTS: The levels of ghrelin and NPY before treatment in acupuncture group and the medication group were lower apparently than those in the healthy control group (all P < 0.01), but the level of leptin was higher appa-rently than that in the healthy control group (P < 0.01). After treatment, the levels of ghrelin and NPY were higher apparently than those before treatment in the acupuncture group (both P < 0.01), and the level of leptin was lower apparently than that before treatment (P < 0.01). All of the above indices in the acupuncture group were improved obviously after treatment as compared with those in the medication group (all P < 0.01). The remarkable and effective rate were 82.5% (33/40) and 32.5% (13/40) and the total effective rate were 95.0% (38/40) and 45.0% (18/40) in the acupuncture group and medication group separately, the results in the acupuncture group were superior to the medication group (both P < 0.01). CONCLUSION: Acupuncture at Sifeng (EX-UE 10) effectively promotes the secretion of ghrelin and NPY and inhibit leptin. It effectively promotes appetite for the children and the efficacy is superior to erkangning syrup.

Timing of antioxidant supplementation is critical in improving anorexia in an experimental model of cancer.

Increased oxidative stress may contribute to cancer anorexia, which could be ameliorated by antioxidant supplementation. methylcholanthrene (MCA) sarcoma-bearing Fisher rats were studied. After tumour inoculation, rats were randomly assigned to standard diet (CTR group, n = 6), or to an antioxidant-enriched diet (AOX group, n = 8). Eight more rats (STD-AOX group) switched from standard to antioxidant diet when anorexia developed. At the end of the study, food intake (FI, g/d), body weight and tumour weight (g) were recorded, and plasma samples were obtained. On day 16, anorexia has appeared only in CTR and STD-AOX animals. At the end of the study, FI in AOX animals was still higher than in the other groups (p = 0.08). No differences in body and tumour weights were observed among groups. However, hydrogen peroxide and interleukin-1ß levels were significantly reduced only in AOX rats. Data obtained suggest that early antioxidant supplementation improves cancer anorexia, ameliorates oxidative stress and reduces inflammation.

Lipid profile and cardiovascular risk in anorexia nervosa; the effect of nutritional treatment.

OBJECTIVE: The aim of this study was to explore the lipid profile in patients with anorexia nervosa (AN), and the changes with refeeding. METHODS: The sample comprised 102 AN outpatients (mean age 22.32 ± 3.17). Blood tests, after 12-hour overnight fast, were performed before refeeding (M(0)) and after weight restoration (M(1)). Total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides (TRG) were determined and the following cardiovascular risk markers were calculated: LDL/HDL and TC/HDL ratios. These cut-off points were considered: TC < 200 mg/dl; HDL > 40 mg/dl; LDL < 100 mg/dl and TRG < 150 mg/dl. RESULTS: The time leading to weight restoration was 8.16 ± 7.35 months. Considering patients with scores higher and lower than the corresponding cut-off points, X²-test revealed a significant difference (M(0)-M(1)) in case of TC (p < 0.05) as well as between LDL/HDL(0) and LDL/HDL(1) (p < 0.05) and between TC/HDL(0) and TC/HDL(1) (p < 0.01). Significant differences were found between HDL(0) and HDL(1) (p < 0.01) and between TRG(0) and TRG(1) (p < 0.01). Significant and negative associations between BMI(0) and TC(0) (r = -0.331; p < 0.05) and between TRG(0) and HDL(0) (r = -0.387; p < 0.05) were found. The association between TRG(1) and LDL(1) was significant and positive. DISCUSSION: Weight restoration tends to decrease the TC/HDL and LDL/HDL ratios despite a considerable percentage of patients maintain scores on the different variables of the lipid profile usually considered at risk.

Preliminary report: vitamin D deficiency in advanced cancer patients with symptoms of fatigue or anorexia.

BACKGROUND: Vitamin D deficiency in noncancer patients is associated with symptoms of fatigue, muscle weakness, and depression. These symptoms are common among advanced cancer patients. We investigated the prevalence of low serum vitamin D levels in cancer patients with fatigue or poor appetite and their association with symptom burden and other correctable endocrine abnormalities. METHODS: This was a retrospective review of 100 consecutive cancer patients with appetite or fatigue scores of ≥4 of 10 referred to a supportive care clinic. We investigated serum levels of 25(OH) vitamin D, cortisol, thyroid-stimulating hormone, and bioavailable testosterone. Symptoms were measured by the Edmonton Symptom Assessment Scale. Serum 25(OH) vitamin D <20 ng/mL was considered deficient; ≥20 ng/mL and <30 ng/mL were considered insufficient. RESULTS: Patients were predominantly male (68%) and white (66%), with a median age of 60 years (range, 27-91 years). Gastrointestinal (30%) and lung (22%) cancers were predominant. Forty-seven patients (47%) were vitamin D deficient and 70 (70%) were insufficient. Thirteen of 70 patients (19%) with vitamin D insufficiency were on supplementation. Vitamin D deficiency was more common among nonwhites (82% versus 36%) and females. No significant association was found between vitamin D and symptoms. Hypogonadic males had a significantly lower mean 25(OH) vitamin D level than eugonadic males. CONCLUSIONS: Low vitamin D levels were highly prevalent among advanced cancer patients with cachexia or fatigue. Vitamin D deficiency was more frequent among nonwhite and female patients. Vitamin D levels were also significantly lower in male patients with hypogonadism.

Decreased plasma ghrelin contributes to anorexia following novelty stress.

We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration via serotonin (5-HT) and melanocortin-4 receptors (MC4R). Each mouse was transferred from group-housed cages to individual cages to establish the novelty stress. We observed the effect of changes in feeding behavior in a novel environment using the method of transferring group-housed mice to individual cages. We investigated the effect of an intracerebroventricular injection of antagonists/agonists of CRF1/2 receptors (CRF1/2Rs), 5-HT(1B)/(2C) receptors (5-HT(1B)/(2C)R), and MC4R to clarify the role of each receptor on the decrease in food intake. Plasma ghrelin levels were also measured. The novelty stress caused a reduction in food intake that was abolished by administering a CRF1R antagonist. Three hours after the novelty stress, appetite reduction was associated with reduced levels of neuropeptide Y/agouti-related peptide mRNA, increased levels of proopiomelanocortin mRNA in the hypothalamus, and a decrease in plasma ghrelin level. Administering a CRF1R antagonist, a 5-HT(1B)/(2C)R antagonist, an MC4R antagonist, exogenous ghrelin, and an enhancer of ghrelin secretion, rikkunshito, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations. We showed that anorexia during a novelty stress is a process in which CRF1R is activated at the early stage of appetite loss and is subsequently activated by a 5-HT(1B)/(2C)R and MC4R stimulus, leading to decreased peripheral ghrelin concentrations.

Glutamine-supplemented total parenteral nutrition improves immunological status in anorectic patients.

OBJECTIVE: Glutamine is an important substrate for critical cells of the immune system, in particular lymphocytes and macrophages, and it is considered a conditionally essential amino acid. Several studies have indicated that glutamine-enriched total parenteral nutrition improves immunologic status and shortens length of stay of critically ill patients. We investigated the effect of total parenteral nutrition supplemented with glutamine on the immune system in anorectic patients. METHODS: Thirty-six anorectic patients were randomized to receive standard parenteral nutrition or parenteral nutrition supplemented with glutamine 0.18 g kg(-1) d(-1) for 20 d. To evaluate the immune system status, we determined serum levels of neopterin and insulin growth factor-1 and lymphocyte count at baseline and after 10 and 20 d from the beginning of the therapy. RESULTS AND CONCLUSIONS: The results showed a significant increase of the serum levels of neopterin after 10 d of treatment with glutamine (26.44 +/- 3.08 versus 6.75 +/- 1.73 nmol/L, P < 0.001), thus proving a probable stimulating action carried out by glutamine on the immune system, as testified by the increase of lymphocytes.

Consequences of protein supplementation for anorexia, expression of immunity and plasma leptin concentrations in parasitized ewes of two breeds.

The periparturient relaxation of immunity (PPRI) against parasites in ewes has a nutritional basis. We investigated whether ewes experience a reduction in food intake (anorexia) during PPRI and if the magnitude of anorexia is affected by host production potential and dietary protein supplementation. We also investigated whether nematode infection is linked to plasma leptin concentrations in periparturient ewes. The experiment was a 2 x 2 x 2 factorial design. Two breeds of twin-bearing/lactating ewes (Greyface cross, G (n 32) and Scottish Blackface, B (n 32)) were used. Half of the ewes were trickle infected with 30,000 larvae of the abomasal parasite Teladorsagia circumcincta per week and the other half were not. During the experiment, all ewes had ad libitum access to a low-protein diet that provided less protein than the recommended allowance. In addition, half of the ewes received a protein supplement that resulted in protein intakes that exceeded recommendations. Nematode infection resulted in a breakdown of immunity to parasites and a reduction in food intake in both breeds. The breeds differed in the extent of PPRI (G ewes having higher faecal egg counts than B ewes), but not in the magnitude of anorexia. Protein supplementation resulted in a reduction in faecal egg counts, but had no effect on the magnitude of anorexia. Plasma leptin concentrations changed significantly over time, but were not affected by protein supplementation or infection. It is concluded that infection with T. circumcincta in periparturient ewes results in anorexia that is not alleviated by protein supplementation and seems unrelated to plasma leptin concentrations.

[Effect of acupuncture at Sifeng (EX-UE 10) on serum leptin in the child of anorexia].

OBJECTIVE: To observe effect of acupuncture at Sifeng (EX-UE 10) on serum leptin level in the child of anorexia, so as to reveal relation between changes of blood leptin level and anorexia of child. METHODS: Forty-two cases were randomly divided into 3 groups. The treatment group A (n = 15) were treated with acupuncture at Sifeng (EX-UE 10), once each week, 3 consecutive sessions constituting one course; the treatment group B (n = 15) were treated with acupuncture at Sifeng (EX-UE 10), once two weeks, 3 consecutive sessions constituting one course; the medication group (n = 12) were treated with oral administration of Lactein tablets, 1 - 2 tablets each time, 3 times each day, 4 weeks constituting one course. RESULTS: The effective rate was 93.3% in the treatment group A and 93.3% in the treatment group B, which were higher than that in the medication group, with a very significant differences (P < 0.01); after treatment, the serum leptin levels in the 3 groups had very significant changes (P < 0.01); the improvement of serum leptin levels in the treatment group A and B were better than that in the medication group (P < 0.05). CONCLUSION: Acupuncture at Sifeng (EX-UE 10) can promote secretion of serum leptin in the child of anorexia, and improve anorexia.

Neural network interactions and ingestive behavior control during anorexia.

Many models have been proposed over the years to explain how motivated feeding behavior is controlled. One of the most compelling is based on the original concepts of Eliot Stellar whereby sets of interosensory and exterosensory inputs converge on a hypothalamic control network that can either stimulate or inhibit feeding. These inputs arise from information originating in the blood, the viscera, and the telencephalon. In this manner the relative strengths of the hypothalamic stimulatory and inhibitory networks at a particular time dictates how an animal feeds. Anorexia occurs when the balance within the networks consistently favors the restraint of feeding. This article discusses experimental evidence supporting a model whereby the increases in plasma osmolality that result from drinking hypertonic saline activate pathways projecting to neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA). These neurons constitute the hypothalamic controller for ingestive behavior, and receive a set of afferent inputs from regions of the brain that process sensory information that is critical for different aspects of feeding. Important sets of inputs arise in the arcuate nucleus, the hindbrain, and in the telencephalon. Anorexia is generated in dehydrated animals by way of osmosensitive projections to the behavior control neurons in the PVH and LHA, rather than by actions on their afferent inputs.

Anorexia in space and possible etiologies: an overview.

Space travelers experience a flight duration-dependent loss in weight and body mass while in a microgravity environment, despite the absence of increased energy expenditure. Anorexia in space can lead to in-flight caloric deficits of 1330 kcal per 70 kg astronaut per day in the presence of abundant food and has a critical effect on endurance and performance. Microgravity, alterations in the light-and-dark cycle, and exposure to radiation energy are the environmental stresses believed to influence appetite, food intake, and gastrointestinal function during space flight. Review of data and recent studies in rodents during microgravity showed a release of stress hormones and complex neuroendocrine and physiologic changes involving the modulation of hypothalamic activity, food intake-related hormones, and cytokines. The shift of dietary preference to carbohydrates, which occurs in astronauts, denotes a stress physiologic response and augments free-plasma tryptophan concentration in the brain, the precursor of the potent anorexic agent, serotonin (5-HT). Alterations of other neuroendocrine mediators, including corticotropin-releasing factor (CRF), coordinate the stress response, leading to a decrease in appetite and gastrointestinal function. Our laboratories used the antiorthostatic tail-suspension technique to successfully mimic some of these anorexia-related stress responses and to directly demonstrate the role of 5-HT in microgravity-related decreased food intake and delayed gastric emptying. Further rodent studies from our laboratories demonstrated the adverse effect of altered dark-and-light cycles on food intake and body weight. Radiation energy, through its documented effects on appetite, probably contributes to the decreased caloric intake by astronauts. Modulation of hypothalamic activity, 5-HT, and CRF play a critical role in anorexia related to microgravity and circadian rhythm alterations. Specific gene knockout mice (e.g., 5-HT or CRF and their respective receptors) may prove fruitful in defining the pathways by which anorexia in space occurs. An understanding of these pathophysiologic problems as they relate to appetite, food intake, gastric emptying and gastrointestinal function, sufficiently to derive successful practical solutions, may lead to a quantitative enhancement of physiologic well-being and performance status, serving as a productive countermeasure in space.

Dietary supplementation with conjugated linoleic acid does not improve nutritional status of tumor-bearing rats.

Tumor necrosis factor-alpha (TNF) is an immunoregulatory cytokine that plays a major role in tumor-induced anorexia and weight loss. Conjugated linoleic acids (CLA) are naturally occurring isomers of linoleic acid that, when added to the diet, improve food intake and body weight in mice injected with TNF. The purpose of the present study was to examine the effects of a diet supplemented with 0.5% CLA on the nutritional status of rats implanted with the Morris 7777 hepatoma. Body weight, food intake, serum levels of insulin-like growth factor, and splenocyte synthesis of TNF were not different in tumor-bearing animals fed CLA versus the control diet. However, insulin levels were increased in both tumor-bearing and control animals given CLA. The 0.5% CLA did not improve the nutritional status nor alter TNF synthesis in hypophagic tumor-bearing rats. The biological significance of increased insulin levels in animals given CLA remains to be determined.

[Effect of fuzheng jianpi recipe on content of trace element and immune function in children with spleen deficiency anorexia].

OBJECTIVE: To evaluate the efficacy and prospect of Fuzheng Jianpi Recipe (FZJPR) in treating children's Spleen deficiency anorexia (CSDA) by means of observing its effect on trace element content and immune function. METHODS: One hundred and thirty cases of CSDA were treated with FZJPR, one dose per day in decoction, orally taken, 30 days for one therapeutic course. Levels of T-lymphocyte subsets, IL-2R, immunoglobulin and trace elements were determined before and after treatment, and compared with those in the control group consisted of 60 healthy children. RESULTS: In the treated group, abnormal figures were shown in T-lymphocyte subsets, especially in lowering of CD3 and CD4 count before treatment, and IgG content was reduced also. After treatment, CD3, CD4, CD4/CD8 ratio as well as IgG and IgA were improved significantly (P < 0.01), IL-2R percentage approached normal. Moreover, the levels of Zn and Fe changed significantly (P < 0.01). CONCLUSION: FZJPR could improve the trace elements content and immune function in CSDA children, so it is effective in treating CSDA.

Role of hypothalamic neuropeptide Y and orexigenic peptides in anorexia associated with experimental colitis in the rat.

Neuropeptide Y (NPY) is thought to play a crucial role in the normal hypothalamic response to starvation. After a period of food restriction, increased release of NPY induces hunger and hyperphagia, and helps to restore body weight to its set point. Persistent anorexia in rats with experimental colitis implies failure of this adaptive feeding response. In vivo NPY release and regional hypothalamic NPY concentrations were measured in rats with trinitrobenzenesulphonic acid (TNBS)-induced colitis, healthy controls and animals pair-fed to match the food intake of the colitic group. Food intake in the colitic group was assessed after administration of NPY and two other potent orexigenic peptides: melanin-concentrating hormone (MCH) and hypocretin (orexin-A). Food intake was decreased by 30-80% below control values for 5 days in the colitic rats. In both the pair-fed and colitic groups, release of NPY in the paraventricular nucleus was significantly increased compared with free-feeding controls. Intraventricular or intrahypothalamic administration of NPY, MCH or hypocretin elicited a feeding response in healthy controls, but not in the colitic group. In summary, animals with TNBS-colitis and anorexia show an appropriate increase in hypothalamic NPYergic activity. However, the failure of NPY and other orexigenic peptides to increase feeding in the colitic group indicates suppression of feeding, either by inhibition of a common downstream hypothalamic neuronal pathway or by induction of one or more potent anorexigenic agents.