Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vagal afferents are extensively distributed in the digestive tract from the oesophagus to the colon. They are involved in the reflex control of normal gastrointestinal (GI) tract function (e.g. secretion and motility) as well as reflexes more characteristic of diseases such as functional dyspepsia and gastroesophageal reflux disease (e.g. vomiting, disordered lower esophageal sphincter relaxation and gastric accommodation). They are also implicated in signalling non-painful sensations (e.g. nausea and early satiety) associated with disease. A variety of receptors has been identified on vagal afferents, which can either enhance (e.g. 5-HT3, CCK1, VR1 and NK1 receptors) or reduce (e.g. ghrelin, leptin, k-opioid and GABAB receptors) activity, offering a range of potential therapeutic targets. Commonly used laboratory species (e.g. rat and mouse) lack an emetic reflex, and the implications of this for models of upper GI disorders have been explored in the light of expanding knowledge of the neuropharmacology of the emetic reflex implicating glutamate, prostanoids, cannabinoids and substance P. Additional pathophysiological roles for vagal afferents (e.g. in thermoregulation, arousal and fatigue) are being investigated, raising the intriguing possibility of the vagus as a target in non-GI disorders.
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PMID:Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction. 1248 26

The aim of achieving a normal or ideal body weight in the treatment of obesity is an obsolete goal. It stems from the time that obesity was not yet seen as a chronic incurable disease. A more realistic treatment goal is to reduce the body weight by 10-15% over a prolonged period of time. This moderate weight loss will result in a decreased risk for and incidence of obesity-associated diseases. Weight reduction and maintenance is countered by a decrease in resting-energy expenditure and in thermogenesis by food intake, a decreased energy expenditure through physical exercise, a reduced fat oxidation, a relative leptin deficiency and an excess of the gastrointestinal hormone ghrelin. Just as with hypertension and diabetes, the only option is life-long management with the normalisation of abnormal values within a given range.
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PMID:[Nutrition and health--ideal body weight for the obese unrealistic; health benefit by moderate sustained weight loss]. 1284 36

For more than 30 years, growth hormone (GH) has been observed to be preferentially secreted during deep, slow-wave sleep (SWS). However, the mechanisms that underlie this robust relationship that links anabolic processes in the body with behavioral rest and decreased cerebral metabolism remain to be elucidated. Current evidence indicates that GH secretion during the beginning of sleep appears to be primarily regulated by GH-releasing hormone (GHRH) stimulation occurring during a period of relative somatostatin withdrawal, which also is associated with elevated levels of circulating ghrelin. Apparently, two populations of GHRH neurons need to be simultaneously active to stimulate, in a coordinated fashion, SWS and pituitary GH release. Pharmacological interventions that are capable of increasing the duration and/or the intensity of SWS such as oral administration of gamma-hydroxybutyrate (GHB), also increase the rate of GH release. Because the normal negative feedback exerted by GH on central GHRH is inoperative in patients with GH deficiency, it is possible that the decreased energy levels and fatigue often reported by GH-deficient adults partly reflect an alteration in sleep-wake regulation. Preliminary data from a sleep study of adults with GH deficiency using wrist actigraphy for 6 nights at home and polysomnography in the laboratory indeed show decreased total sleep time and increased sleep fragmentation in GH-deficient patients as compared with normal controls.
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PMID:Reciprocal interactions between the GH axis and sleep. 1513 71

We tested the hypothesis that leptin acts centrally to differentially modulate the ultradian communication of leptin, insulin and ghrelin with the hypothalamus. The ultradian fluctuation of these hormones in plasma after central leptin gene therapy was analyzed. Increased leptin transgene expression in the hypothalamus significantly decreased energy intake and body weight concomitant with severe hypoleptinemia and hypoinsulinemia resulting from drastically suppressed peak heights with unchanged frequency discharge of these hormones. Ghrelin secretion was, however, increased solely due to increased pulse amplitude. In pair-fed control rats leptin and ghrelin secretion was unchanged. In conclusion, independent of restraint on caloric intake and weight, leptin acting centrally modulates only the pulse amplitude of ultradian rhythmicity of the three afferent signals involved in the hypothalamic integration of energy balance. Since rhythmic discharge patterns dictate target response of hormones, these findings reveal a novel hypothalamic action of leptin in the pathophysiology of the obesity-dependent metabolic syndrome.
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PMID:Central leptin differentially modulates ultradian secretory patterns of insulin, leptin and ghrelin independent of effects on food intake and body weight. 1593 48

To ascertain the mechanisms underlying low caloric intake and low body weight in the Lou/C rat, the circulating hormone levels and gene expression of hypothalamic peptides and receptors important in energy balance and the induction of suppressor of cytokine signalling 3 (SOCS3) gene expression in response to leptin challenge were compared with Wistar rats. Plasma leptin levels were lower in the Lou/C rat, as were levels of rat corticosterone, TSH and T4 but not T3. Ghrelin levels were higher in the Lou/C rat. Total leptin receptor (Ob-R) and the long form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate (ARC) and ventromedial nuclei (VMN) in Lou/C rat. Ghrelin receptor expression in the ARC and VMN was lower in Lou/C than in Wistar rats. However, agouti gene-related peptide (AgRP) and neuropeptide Y (NPY) gene expression were higher in the Lou/C rat. There was no difference in the level of cocaine- and amphetamine-regulated transcript gene expression in the ARC, but both were higher in the paraventricular nuclei of the Lou/C breed. There was no difference in Ob-R gene expression in, or [(125)I]leptin binding to, the choroid plexus. SOCS3 mRNA induction in response to leptin was lower in the Lou/C rat. This study reveals that the comparatively low plasma leptin, TSH and T4 levels, and high ghrelin levels together with high levels of AgRP and NPY gene expression seen in the Lou/C rat are indicative of a strong drive to eat and decreased energy expenditure, which are in direct opposition to the comparatively low body weight and adiposity of this rat strain.
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PMID:Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats. 1700 58

Social isolation is associated with increased risks of mortality and morbidity. In this study, we show that chronic individual housing accelerated body weight gain and adiposity in KK mice but not C57BL6J mice, and fully developed diabetes in KKA(y) mice. Individually housed KK and KKA(y) mice increased body weight gain over the initial 2 wk without increased daily average food consumption compared with group-housed animals. The individually housed KK and KKA(y) mice then gradually increased food consumption for the next 1 wk. The chronic social isolation-induced obesity (SIO) was associated with hyperleptinemia and lower plasma corticosterone and active ghrelin levels but not hyperinsulinemia. Elevated plasma leptin in the SIO suppressed expression of 5-HT2C receptor in white adipose tissue. The SIO was also associated with decreased expression of beta3-adrenergic receptors in white adipose tissue and hypothalamic leptin receptor, which might be secondary to the enhanced adiposity. Interestingly, social isolation acutely reduced food consumption and body weight gain compared with group-housed obese db/db mice with leptin receptor deficiency. Social isolation-induced hyperglycemia in KKA(y) mice was associated with increased expression of hepatic gluconeogenetic genes independent of insulin. These findings suggest that social isolation promotes obesity due to primary decreased energy expenditure and secondary increased food consumption, which are independent of the disturbed leptin signaling, in KK mice, and develops into insulin-independent diabetes associated with increased expression of hepatic gluconeogenetic genes in KKA(y) mice. Thus, social isolation can be included in the environmental factors that contribute to the development of obesity and type 2 diabetes.
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PMID:Social isolation affects the development of obesity and type 2 diabetes in mice. 1764 Sep 95

General gastrointestinal dysmotility occurs in patients with irritable bowel syndrome (IBS). Ghrelin seems to play an important role in regulating gastrointestinal motility. The present study was undertaken, therefore, to establish the possible role of ghrelin in the pathophysiology of IBS. Thirty-seven patients with IBS (19 had IBS-constipation and 18 IBS-diarrhoea) were included in this study. Ten healthy volunteers served as controls. After overnight fast, blood samples were drawn from patients and controls, and a gastroduodenal endoscopy was performed. Biopsies were taken from oxyntic mucosa and duodenum. Ghrelin cell density was determined by computer image analysis after immunohistochemical staining of the tissues. Total and active ghrelin were detected in tissue extracts and plasma by commercially available RIA and ELISA Kits. The density of ghrelin-immunoreactive cells in the oxyntic mucosa was significantly lower in IBS-constipation and significantly higher in IBS-diarrhoea patients than healthy controls (P<0.0001 and <0.0001, respectively). There was no statistical difference in total or active ghrelin between IBS patients and controls, regarding tissue extracts or plasma. In order to compensate for the increase and decrease in the ghrelin cell density, the synthesis and release of ghrelin may be decreased and increased in IBS-diarrhoea and IBS-constipation patients, respectively. It has been speculated that this compensatory mechanism may be subjected from time to time to fatigue with the subsequent increased and decreased synthesis and release of ghrelin in IBS-diarrhoea and IBS-constipation with a subsequent intermittent diarrhoea or constipation seen in these patients, respectively.
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PMID:Ghrelin in patients with irritable bowel syndrome. 1942 95

Previous research demonstrated increased plasma ghrelin concentrations in beef cattle when intake of a high-grain diet was restricted. Two experiments were conducted to determine whether differences in DMI influenced plasma ghrelin concentrations when energy intake was similar but cattle were in either an anabolic or a catabolic state. In Exp. 1, five steers (BW = 592.6 +/- 9.3 kg) were offered dietary treatments of 1) 50:50 hay:concentrate (HY) to meet the NE(m) requirement and were supplied an additional 3.4 Mcal of NE(g) daily, 2) or a diet composed of 10:90 hay:concentrate but were limit-fed to achieve an energy intake similar to that of the HY steers (LFC). The LFC treatment met the NE(m) requirement of each steer and supplied 3.6 Mcal of NE(g) daily. The experiment was conducted as a crossover design composed of 2 21-d periods. In the first period, 2 steers were assigned to the HY treatment and 3 steers were assigned to the LFC treatment. On d 21 after initiation of the dietary treatment, serial blood samples were collected via indwelling jugular catheter, using periods of frequent sampling in which samples were collected at 15-min intervals. The periods of frequent sampling were spread throughout the beginning, middle, and end of the 12-h feeding interval. After the first period, steers were weighed, dietary treatments were switched between steer groups, and intake amounts were recalculated on the basis of the first-period ending BW. The second-period adaptation and sampling were repeated as described for the first period. Plasma samples were assayed for ghrelin, insulin, GH, and NEFA concentrations. Experiment 2 was conducted using the same methodology as Exp. 1, except that steers were in a catabolic state. Five steers (BW = 718.3 +/- 12.8 kg) were offered the HY or LFC diet at an amount that would supply 80% of the NE(m) required to maintain BW. For Exp. 1, energy intake was sufficient to result in similar (P = 0.14) BW gains between treatment groups. Experiment 2 energy intake resulted in a loss of BW that was similar (P = 0.66) between treatment groups. In both experiments, the decreased energy density of the HY diet resulted in greater (P < or = 0.001) DMI for HY steers compared with LFC steers. Regardless of catabolic or anabolic state, plasma ghrelin, GH, and insulin were similar (P > or = 0.44) when energy intakes were similar despite differences in DMI between HY and LFC steers. Plasma NEFA concentrations were similar (P > or = 0.45) between treatment groups in an anabolic state but tended to differ (P = 0.09) as a result of treatment for cattle in the catabolic state. These data are consistent with the hypothesis that quantity of DMI does not influence plasma ghrelin concentrations of steers when energy intake is similar.
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PMID:Plasma ghrelin concentrations of beef cattle consuming a similar amount of dietary energy supplied by different ingredients. 2019 Jan 64

Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight-bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and nonathletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotropin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes.
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PMID:Influence of ghrelin and adipocytokines on bone mineral density in adolescent female athletes with amenorrhea and eumenorrheic athletes. 2095 63

The treatment of anorexia in chronic hemodialysis patients is based on a therapeutic strategy which includes optimal dialysis dose (through daily or nocturnal dialysis), support of food intake (through nutritional counseling and oral nutritional supplements), counteractive action to anorexic agents (e.g., inflammatory cytokines and low levels of branched chain amino acids), stimulation of appetite (ghrelin), and attention to associated symptoms (e.g., symptoms of depression and anxiety, fatigue, other comorbidities). However, the fact remains that the studies so far conducted are insufficient both in terms of number and quality to provide guidelines for clinical and research purposes. Randomized, controlled trials are needed in the future to define the best strategy to counteract anorexia in maintenance dialysis patients.
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PMID:Interventions to counteract anorexia in dialysis patients. 2119 11


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