Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in triglyceride synthesis, have increased energy expenditure and therefore are resistant to obesity. Because ambient temperature can significantly affect energy expenditure in mice, we undertook these studies to determine the effects of different ambient temperatures on energy expenditure, food intake, and thermoregulation in DGAT1-deficient [Dgat1(-/-)] mice. Dgat1(-/-) mice had increased energy expenditure irrespective of changes in the ambient temperature. Although core temperature was normal, surface temperature was increased in Dgat1(-/-) mice, most likely reflecting an active mechanism to dissipate heat from increased thermogenesis. Dgat1(-/-) mice had increased food intake at baseline, and this hyperphagia became more pronounced upon exposure to cold. When fasted in a cold environment, Dgat1(-/-) mice developed hypothermia, which was associated with hypoglycemia. These results suggest that the hyperphagia in Dgat1(-/-) mice is a secondary mechanism that compensates for the increased utilization of fuel substrates. Our findings offer insights into the mechanisms of hyperphagia and increased energy expenditure in a murine model of obesity resistance.
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PMID:Analysis of energy expenditure at different ambient temperatures in mice lacking DGAT1. 1238 46

Lower limb compartment syndrome is an unusual but severe complication of prolonged surgery more than four hours in lithotomy position. It is usually a consequence of hypoperfusion of the lower extremities and muscle necrosis may occur. Several risk factors are pointed out: trendelenburg, the hardness of operating table, hypothermia, control hypotension, occlusion of arterial blood flow of the lower extremity, arteritis (and smoking), diabetes, obesity, arterial hypertension, myopathy and an important muscle mass. The symptoms are postoperative pain with neurological signs. A rapid diagnosis and aggressive management (i.e. resuscitation and aponevrotomy) is recommended. Neurological sequelae are sometimes invalidating. Reporting a case of bilateral syndrome, we reviewed the literature and describe the present diagnosis and therapeutic management as well as prevention modalities of this iatrogenic complication.
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PMID:[Bilateral compartment syndrome after colorectal surgery in the lithotomy position]. 1240 49

Hypothalamic proopiomelanocortin (POMC) gene expression is reduced in many forms of obesity and diabetes, particularly in those attributable to deficiencies in leptin or its receptor. To assess the functional significance of POMC in mediating metabolic phenotypes associated with leptin deficiency, leptin-deficient mice bearing a transgene expressing the POMC gene under control of the neuron-specific enolase promoter were produced. The POMC transgene attenuated fasting-induced hyperphagia in wild-type mice. Furthermore, the POMC transgene partially reversed obesity, hyperphagia, and hypothermia and effectively normalized hyperglycemia, glucosuria, glucose intolerance, and insulin resistance in leptin-deficient mice. Effects of the POMC transgene on glucose homeostasis were independent of the partial correction of hyperphagia and obesity. Furthermore, the POMC transgene normalized the profile of hepatic and adipose gene expression associated with gluconeogenesis, glucose output, and insulin sensitivity. These results indicate that central POMC is a key modulator of glucose homeostasis and that agonists of POMC products may provide effective therapy in treating impairments in glucose homeostasis when hypothalamic POMC expression is reduced, as occurs with leptin deficiency, hypothalamic damage, and aging.
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PMID:Transgenic neuronal expression of proopiomelanocortin attenuates hyperphagic response to fasting and reverses metabolic impairments in leptin-deficient obese mice. 1457 85

Obese (f/f) Koletsky rats lack the leptin receptor (LR), whereas their lean (F/?) counterparts bear a fully functional LR. By using f/f and F/? rats, we studied whether the LR is involved in lipopolysaccharide (LPS)-induced fever and hypothermia. The body temperature responses to LPS (10 or 100 microg/kg iv) were measured in Koletsky rats exposed to a thermoneutral (28 degrees C) or cool (22 degrees C) environment. Rats of both genotypes responded to LPS with fever at 28 degrees C and with dose-dependent hypothermia at 22 degrees C. The fever responses of the f/f and F/? rats were identical. The hypothermic response of the f/f rats was markedly prolonged compared with that of the F/? rats. The prolonged hypothermic response to LPS in the f/f rats was accompanied by enhanced NF-kappaB signaling in the hypothalamus and an exaggerated rise in the plasma concentration of tumor necrosis factor (TNF)-alpha. The f/f rats did not respond to LPS with an increase in the plasma concentration of corticosterone or adrenocorticotropic hormone, whereas their F/? counterparts did. The hypothermic response to TNF-alpha (80 microg/kg iv) was markedly prolonged in the f/f rats. These data show that the LR is essential for the recovery from LPS hypothermia. LR-dependent mechanisms of the recovery from LPS hypothermia include activation of the anti-inflammatory hypothalamo-pituitary-adrenal axis, inhibition of both the production and hypothermic action of TNF-alpha, and suppression of inflammatory (via NF-kappaB) signaling in the hypothalamus.
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PMID:A new function of the leptin receptor: mediation of the recovery from lipopolysaccharide-induced hypothermia. 1538 70

A 67-year-old man underwent laparoscopic surgery for rectal cancer in the lithotomy position. After surgery he complained of bilateral lower limb pain, swollen legs, and sensory disturbance. The serum creatine kinase value was 46 662 U/l. Venography demonstrated compression from outside without any obstruction. The T2 image of magnetic resonance imaging (MRI) showed a massive swollen muscle and a partial high-intensity area in the bilateral lower limbs. The posterior compartment pressures of lower legs were high (gastrocnemius muscle: 30 mmHg [right] and 44 mmHg [left]). Compartment syndrome (superficial posterior compartment) was thus diagnosed. He underwent a fasciotomy using the single dorsal approach and the administration of a large amount of fluid. He recovered well without any motor or sensory deficits. Compartment syndrome is rare, occurring only once in every 3500 cases, but it is a severe complication of surgery in the lithotomy position. Several risk factors have been pointed out: including prolonged operation, hardness of the operating table, obesity, dehydration, and hypothermia. To prevent compartment syndrome, appropriate positioning during surgery is therefore essential. To make a timely diagnosis and identify the precise location of muscle edema, the T2 image of MRI is useful.
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PMID:Compartment syndrome of bilateral lower extremities following laparoscopic surgery of rectal cancer in lithotomy position: report of a case. 1712 45

We document in vitro and in vivo effects of a novel, selective cannabinoid CB(1) receptor inverse agonist, Imidazole 24b (5-(4-chlorophenyl)-N-cyclohexyl-4-(2,4-dichlorophenyl)-1-methyl-imidazole-2-carboxamide). The in vitro binding affinity of Imidazole 24b for recombinant human and rat CB(1) receptor is 4 and 10 nM, respectively. Imidazole 24b binds to human cannabinoid CB(2) receptor with an affinity of 297 nM; in vitro, it is a receptor inverse agonist at both cannabinoid CB(1) and CB(2) receptors as it causes a further increase of forskolin-induced cAMP increase. Oral administration of Imidazole 24b blocked CP-55940-induced hypothermia, demonstrating cannabinoid CB(1) receptor antagonist efficacy in vivo. Using ex vivo autoradiography, Imidazole 24b resulted in dose-dependent increases in brain cannabinoid CB(1) receptor occupancy (RO) at 2h post-dosing in rats, indicating that approximately 50% receptor occupancy is sufficient for attenuation of receptor agonist-induced hypothermia. Imidazole 24b administered to C57Bl/6 mice and to dietary-induced obese (DIO) Sprague-Dawley rats attenuated overnight food intake with a minimal effective dose of 10 mg/kg, p.o. Administration had no effect in cannabinoid CB(1) receptor-deficient mice. DIO rats were dosed orally with vehicle, Imidazole 24b (1, 3 or 10 mg/kg), or dexfenfluramine (3 mg/kg) for 2 weeks. At 3 mg/kg, Imidazole 24b reduced cumulative food intake, leading to a non-significant decrease in weight gain. Imidazole 24b at 10 mg/kg and dexfenfluramine treatment inhibited food intake and attenuated weight gain. These findings suggest that selective cannabinoid CB(1) receptor inverse agonists such as Imidazole 24b have potential for the treatment of obesity.
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PMID:Characterization of a novel and selective cannabinoid CB1 receptor inverse agonist, Imidazole 24b, in rodents. 1802 63

The obesogenic effect of a high-fat (HF) diet is counterbalanced by stimulation of energy expenditure and lipid oxidation in response to a meal. The aim of this study was to reveal whether muscle nonshivering thermogenesis could be stimulated by a HF diet, especially in obesity-resistant A/J compared with obesity-prone C57BL/6J (B/6J) mice. Experiments were performed on male mice born and maintained at 30 degrees C. Four-week-old mice were randomly weaned onto a low-fat (LF) or HF diet for 2 wk. In the A/J LF mice, cold exposure (4 degrees C) resulted in hypothermia, whereas the A/J HF, B/6J LF, and B/6J HF mice were cold tolerant. Cold sensitivity of the A/J LF mice was associated with a relatively low whole body energy expenditure under resting conditions, which was normalized by the HF diet. In both strains, the HF diet induced uncoupling protein-1-mediated thermogenesis, with a stronger induction in A/J mice. Only in A/J mice: 1) the HF diet augmented activation of whole body lipid oxidation by cold; and 2) at 30 degrees C, oxygen consumption, total content, and phosphorylation of AMP-activated protein kinase (AMPK), and AICAR-stimulated palmitate oxidation in soleus muscle was increased by the HF diet in parallel with significantly increased leptinemia. Gene expression data in soleus muscle of the A/J HF mice indicated a shift from carbohydrate to fatty acid oxidation. Our results suggest a role for muscle nonshivering thermogenesis and lipid oxidation in the obesity-resistant phenotype of A/J mice and indicate that a HF diet could induce thermogenesis in oxidative muscle, possibly via the leptin-AMPK axis.
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PMID:Induction of muscle thermogenesis by high-fat diet in mice: association with obesity-resistance. 1849 79

Dietary supplementation with resveratrol may produce calorie restriction-like effects on metabolic and longevity endpoints in mice. In this study, we sought to determine whether resveratrol treatment elicited other hallmark changes associated with calorie restriction, namely bradycardia and decreased body temperature. We found that during short-term treatment, wild-type mice on a calorie-restricted diet experienced significant decreases in both heart rate and body temperature after only 1 day whereas those receiving resveratrol exhibited no such change after 1 wk. We also used ob/ob mice to study the effects of long-term treatment because previous studies had indicated the therapeutic value of resveratrol against the linked morbidities of obesity and diabetes. After 12 wk, resveratrol treatment had produced no changes in either heart rate or body temperature. Strikingly, and in contrast to previous findings, we found that resveratrol-treated mice had significantly reduced endurance in a treadmill test. Quantitative reverse transcriptase-polymerase chain reaction suggested that a proposed target of resveratrol, Sirt1, was activated in resveratrol-treated ob/ob mice. Thus, we conclude that the bradycardia and hypothermia associated with calorie restriction occur through mechanisms unaffected by the actions of resveratrol and that further studies are needed to examine the differential effects of resveratrol in a leptin-deficient background.
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PMID:Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction. 1905 39

Energy balance to prevent the development of obesity is dependent on energy expenditure. Although physical activity is the dominant mechanism for dissipating excess energy, a system of thermogenesis that evolved to protect the body from hypothermia is based upon the uncoupling of oxidative phosphorylation in brown adipocytes by the mitochondrial uncoupling protein (UCP1). It has been shown that upregulation of UCP1 by genetic manipulations or pharmacological agents can reduce obesity and improve insulin sensitivity. Recent evidence has shown the existence of two sources for brown adipocytes, one appearing as discrete brown fat depots during fetal development and the other appears during post-natal development as diffuse populations in traditional white fat depots. The latter can be induced by adrenergic stimulation depending on the genetic background of the animals and the nutritional environment. Understanding the biological and environmental factors controlling the expression of these two brown adipocyte populations promises to provide new strategies by which enhanced thermogenesis can be used to reduce obesity.International Journal of Obesity (2008) 32, S32-S38; doi:10.1038/ijo.2008.236.
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PMID:UCP1: its involvement and utility in obesity. 1913 89

Nutritional status can impact dopamine systems in a manner that might be important to understanding possible common neurobiological mechanisms that mediate abnormal compulsive food (e.g., obesity) and drug taking. Limiting food intake, for example, can increase sensitivity to the behavioral effects of indirect-acting dopamine receptor agonists. Much less is known regarding possible diet-induced changes in sensitivity to direct-acting dopamine receptor drugs. The present study investigated the effects of a high fat diet and of food restriction on sensitivity of rats to the behavioral effects of a direct-acting dopamine receptor agonist and a dopamine receptor antagonist. Free access to high fat chow increased sensitivity to quinpirole-induced yawning without changing sensitivity to raclopride-induced catalepsy or quinpirole-induced hypothermia. Food restriction (10 g/day) decreased sensitivity to quinpirole-induced yawning and raclopride-induced catalepsy without affecting sensitivity to quinpirole-induced hypothermia. Free access to a standard chow restored sensitivity to the behavioral effects of both drugs in rats that were previously food-restricted but not in rats that previously ate a high fat diet. These data confirm that food restriction can decrease sensitivity to behavioral effects of direct-acting dopamine receptor drugs, they provide evidence (i.e., no change in hypothermic effects) indicating that these changes are not due to pharmacokinetic mechanisms, and they provide initial evidence showing enhanced sensitivity to behavioral effects of dopamine receptor drugs in rats eating a high fat diet. These changes in sensitivity of dopamine systems could be relevant to understanding the impact of nutrition on therapeutic and recreational drug use.
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PMID:High fat diet and food restriction differentially modify the behavioral effects of quinpirole and raclopride in rats. 1932 48


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