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)

The eating disorder bulimia nervosa is characterized by alternating periods of strict dieting and overeating. Patients also report mood fluctuations, frequent eating related thoughts, fear of loss of control over eating, impairment of cognitive abilities such as concentration, and somatic complaints. The present study attempted to clarify to what extent these symptoms are consequences of the dieting behavior. Nine healthy young women, classified as unrestrained eaters, were set on a intermittent dieting schedule over 4 weeks. Four days each week (Tue, Wed, Thu, Fri) they had to reduce their intake below 600 kcal/day, the other 3 days they could eat without restrictions. Psychological variables were assessed by means of a standardized diary. Biological indices of starvation were also measured repeatedly. There was no substantial weight loss after the 4 weeks, although subjects had significantly increased levels of beta-hydroxybutyric acid during the dieting periods, and decreased levels of t3 after 2 weeks. The reported tendency to overeat and the actual calorie intake during the days of unlimited access to food showed a significant increase over the 4-week period. Eating-related thoughts, feelings of hunger, and fear of loss of control were significantly more frequent during periods of dieting, compared to days of normal eating. Subjects also reported worse mood, heightened irritability, difficulties concentrating, and increased fatigue. These results suggest that a substantial part of symptoms of bulimic patients might be associated with the frequent periods of an extremely restrained eating behavior.
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PMID:Biological and psychological correlates of intermittent dieting behavior in young women. A model for bulimia nervosa. 880 34

Young growing animals appear to have significantly reduced "nutritional to short periods of unstressed starvation compared with adults, with resultant growth arrest and/or atrophy of diaphragm (Dia) muscle fibers. The aim of this study was to assess in an adolescent rat model of acute nutritional deprivation (ND; 72 h) the impact of insulin-like growth factor I (IGF-I), with or without added growth hormone (GH), on the cross-sectional areas (CSA) of individual Dia muscle fibers. Five groups were studied: 1) control (Ctr); 2) ND; 3) ND given IGF-I (ND/IGF-I); 4) ND given GH (ND/GH); and 5) ND given a combination of IGF-I and GH (ND/IGF-I/GH). IGF-I was given by a subcutaneously implanted osmotic minipump (200 microg/day), whereas GH was administered twice daily by a subcutaneous injection (250 microg every 12 h). Isometric contractile and fatigue properties of the Dia were determined in vitro. Forces were normalized for muscle CSA (i.e., specific force). Dia fiber type proportions were determined histochemically, and fiber CSA was quantified by using a computer-based image-processing system. Total serum IGF-I concentrations were significantly reduced in ND and ND/GH animals, compared with Ctr, and elevated in the groups receiving IGF-I. The provision of growth factors did not alter the contractile or fatigue properties of ND animals. Dia fiber type proportions were similar among the groups. In ND animals, there was a significant reduction in the CSA of types I, IIa, IIx, and IIc Dia fibers compared with Ctr. The administration of IGF-I alone or in combination with GH to ND animals significantly diminished the reduction in Dia fiber size. GH alone had no effect on Dia fiber size in ND animals. We conclude that with acute ND the peripheral resistance to the action of GH appears to be bypassed by the administration of IGF-I alone or in combination with GH.
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PMID:Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats. 910 40

1. In normal non-exercised skeletal muscles in mice, the activity of histidine decarboxylase (HDC), the enzyme which forms histamine, was very low. 2. HDC activity in the quadriceps femoris muscle was markedly elevated following contractions evoked by even a few minutes of direct electrical stimulation, peaking at 8-12 h following contraction lasting 10 min, and gradually decreasing during the 24 h following contraction. The elevation in HDC activity depended on the duration and strength of stimulation. 3. Direct electrical stimulation induced a quantitatively similar elevation of HDC activity in the muscles of mast-cell-deficient mice (W/Wv mice). 4. Prolonged walking at a speed of 6 m min-1 for up to 6 h with a 30 min rest period at 3 h also elevated muscle HDC activity, the magnitude of the elevation being related to the duration of the walking. Repeated exercise (training) for several days diminished the elevation of muscle HDC activity induced by walking. In contrast, starvation augmented the elevation of muscle HDC activity induced by walking. 5. Intraperitoneal injection of interleukin-1beta (IL-1beta) also elevated muscle HDC activity in a dose-dependent manner, as little as 1 microg kg-1 of IL-1 producing a significant elevation of muscle HDC activity. 6. IL-1beta was immunohistochemically detected in normal non-exercised quadriceps femoris muscle. We could not detect a significant increase in IL-1beta after exercise in the muscle or in serum: it may be below the level of detection. 7. On the basis of these results, together with those reported previously and the known actions of histamine, we propose that an elevation of HDC activity and generation of histamine occur in skeletal muscle following muscle contraction possibly as a result of induction by IL-1beta and that the histamine may be involved in fatigue in skeletal muscle as part of a defence mechanism preventing damage to the muscle.
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PMID:Induction of histidine decarboxylase in skeletal muscle in mice by electrical stimulation, prolonged walking and interleukin-1. 957 6

Six amino acids are metabolized in resting muscle. They are leucine, isoleucine, valine, asparagine, aspartate, and glutamate. These amino acids provide the amino groups and probably the ammonia required for synthesis of glutamine and alanine, which are released in excessive amounts in the postabsorptive state and during ingestion of a protein-containing meal. Only leucine and part of the isolecine molecule can be oxidized in muscle as they are converted to acetyl-CoA. The other carbon skeletons are used solely for de novo synthesis of TCA-cycle intermediates and glutamine. The carbon atoms of the released alanine originate primarily from glycolysis of blood glucose and from muscle glycogen (about half each in resting conditions). After consumption of a protein-containing meal, BCAA and glutamate are taken up by muscle and their carbon skeletons are used for de novo synthesis of glutamine. About half of the glutamine released from muscle originates from glutamate taken up from the blood, both after overnight starvation, after prolonged starvation, and after consumption of a mixed meal. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells, and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates in muscle during the first 10 min of exercise. The increase in concentration of TCA-cycle intermediates probably is needed to increase the flux of the TCA-cycle and meet the increased energy demand of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen-depleted muscles, and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen-depleted muscles, but only allow exercise at 40-50% of Wmax. One-leg exercise leads to the net breakdown of muscle protein. The liberated amino acids are used for synthesis of TCA-cycle intermediates and glutamine. Today, the importance of this process in endurance exercise in the field (running or cycling) in athletes who ingest carbohydrates is not clear. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen-depleted muscles due to insufficient TCA-cycle anaplerosis, and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle are suggested to play a central role in the energy metabolism of the exercising muscle.
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PMID:Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. 969 93

Medium-chain acyl-CoA dehydrogenase (MCAD) is an enzyme responsible for large part of mitochondrial beta-oxidation of fatty acids and therefore stays on key position of cellular energy supply. In case of its deficiency, starvation, rapid growth periods or infections may cause fatal lack of energy, especially in the first years of life. MCAD deficiency is inherited in an autosomal recessive manner and it has been shown to be rather common in some European countries (Great Britain 1 in 6,000, Switzerland 1 in 10,000). In Caucasoid populations one mutation, the 985A>G transition, causing the amino acid substitution K329E, accounts for about 90% of all mutant MCAD alleles. Here we present data about screening the Estonian population for this mutation. We analyzed the DNA from 1,098 persons from all regions of Estonia (all newborns born in one month) and found 5 heterozygotes for 985A>G, that makes the carrier frequency 1 in 220 and the frequency of possibly affected homozygotes 1 out of 193,000. No mutant alleles were found among the samples of the children, who had unclear diagnosis for death during the years 1994 and 1995.
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PMID:Mutation 985A>G in the MCAD gene shows low incidence in Estonian population. 1067 47

Feeding is a complex process responsive to sensory information related to sight and smell of food, previous feeding experiences, satiety signals elicited by ingestion and hormonal signals related to energy balance. Dopamine released in specific brain regions is associated with pleasurable and rewarding events and may reinforce positive aspects of feeding. Dopamine also influences initiation and coordination of motor activity and is required for sensorimotor functions. Thus, dopamine may facilitate integration of sensory cues related to hunger, initiating the search for food and its consumption. Dopaminergic neurons in the substantia nigra and ventral tegmental area project to the caudate putamen and nucleus accumbens, where they modulate movement and reward. There are projections from the nucleus accumbens to the lateral hypothalamus that regulate feeding. Dopamine-deficient mice (Dbh(Th/+), Th-/-; hereafter DD mice) cannot synthesize dopamine in dopaminergic neurons. They gradually become aphagic and die of starvation. Daily treatment of DD mice with L-3,4-dihydroxyphenylalanine (L-DOPA) transiently restores brain dopamine, locomotion and feeding. Leptin-null (Lep(ob/ob)) mice exhibit obesity, decreased energy expenditure and hyperphagia. As the hypothalamic leptin-melanocortin pathway appears to regulate appetite and metabolism, we generated mice lacking both dopamine and leptin (DD x Lep(ob/ob)) to determine if leptin deficiency overcomes the aphagia of DD mice. DD x Lep(ob/ob) mice became obese when treated daily with L-DOPA, but when L-DOPA treatment was terminated the double mutants were capable of movement, but did not feed. Our data show that dopamine is required for feeding in leptin-null mice.
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PMID:Dopamine is required for hyperphagia in Lep(ob/ob) mice. 1080 66

This paper examines three aspects of hunger disease: the effect of initial fat stores on macronutrient fuel selection during total starvation (no energy) and how it influences survival; the effects of different rates of weight loss on tissue and body function; and the importance of appetite sensations, including hunger, during malnutrition and during enteral and parenteral nutritional support. Long-term starvation studies in humans reveal major differences in fat carbohydrate and protein metabolism between lean and obese subjects, including a 2-4-fold lower contribution of protein oxidation to energy expenditure in obese subjects, which ensures that more of the excess body fat is oxidized. The rate of weight loss, determined by recent dietary intake, can have major effects on tissue and body function, including wound healing, the acute phase protein response, muscle fatigue and psychological/behavioural function in both clinical and non-clinical settings. In depleted states uncomplicated by disease, changes in appetite sensations can result in energy intakes as high as 6000 to 10,000 kcal/day ( 25-42 MJ/day). Long-term enteral tube feeding and parenteral nutrition are associated with frequent disturbances in appetite sensations, and in those able to eat normally they tend to add rather than replace oral intake to an extent that appears to depend on the regimen. It is concluded that 1) differences between lean and obese subjects in macronutrient fuel selection during starvation are adaptive because they optimize survival in both groups of subjects; 2) the rate of weight loss in health and disease has a major effect on certain tissue and body functions, independently of the magnitude of weight loss; and 3) clinically relevant disturbances in appetite sensations are common subjects receiving long-term enteral and parenteral nutrition. The clinical modulation of all these variables would be aided by greater knowledge of the mechanisms involved.
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PMID:Hunger disease. 1110 87

From all nutritional variables optimal energy supply is considered as most vital for human performance. It is postulated that lack of energy homeostasis is the basic problem in the development of overtraining. Most if not all clinical symptoms are directly or indirectly related to the physiological mechanisms of energy homeostasis. The rapidly increasing knowledge in the field of body weight control with several new regulatory neuro-peptides such as leptin, will give new opportunities to tackle this unbalance between training load and energy availability. The central role of leptin and insulin as adiposity signals has focussed attention on the anti-obesity aspects of leptin. However as member of the cytokine family, leptin is also closely linked to the immune and reproductive system. New data indicates clearly the dual function of leptin at both ends at the energy balance; starvation vs. overfeeding. It links also nutrition to the reproductive system. Lack of available energy has a much greater impact on leptin levels than exercise stress. It is suggested that application of the rapidly increasing knowledge in the obesity field will benefit the research on the mechanisms involved in the derailment of the delicate balance between training load and energy homeostasis in athletes.
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PMID:The concept of energy homeostasis for optimal health during training. 1189 92

When a mouse is put into a cylinder too narrow for it to turn (its front end being blocked with a thin plastic strip), the mouse gnaws away the plastic to escape. Hence, the weight reduction in the plastic can be used as an index of 'gnawing activity (GA).' GA was high at first, but decreased with time. Training augmented GA, but not the activity of the histamine-forming enzyme (histidine decarboxylase [HDC]: a proposed marker of muscle fatigue) in the masseter muscle. In trained mice, GA was higher at night than in the daytime, and was decreased by starvation. In mice prevented from reaching the strip, the elevation of serum cortisol was greater than that seen in mice able to gnaw at it. As such gnawing is a form of voluntary behavior, these results suggest that our experimental system may be useful for (i) the quantitative study of voluntary muscle activity associated with physical or mental fatigue or motivation, and (ii) the study of an animal's response to stress when it has, or alternatively does not have, an apparent way of escape.
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PMID:Gnawing behavior of a mouse in a narrow cylinder: a simple system for the study of muscle activity, fatigue, and stress. 1221 15

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel--a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)-it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.
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PMID:Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia. 1281 7


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