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)

Obesity is at present one of the most important health risk factors in developed countries. Several studies show significant involvement of genetic factors. A gene called ob is active in the adipose tissue and its product leptin is secreted from adipocytes. Fully functional leptin receptors (encoded by the ob/R gene, also db) have been found in highest numbers in the hypothalamus and therefore it was suggested that it is the leptin plasma level which in forms the brain about total body fat mass and calories intake. Using this pathway it can directly influence a balance between food intake and energy expenditure. The phenotype of ob/ob mutant mice is characterized by severe obesity, NIDDM (non insulin dependent diabetes mellitus), diminished fertility and hypothermia. Db/db mutant mice show a similar phenotype, here the defect lies in the block of leptin receptor downstream signalling. After leptin administration, it was possible to correct the defect only in the ob/ob, but not db/db mice. There is a positive correlation between body mass index and leptin plasma level in humans and no obese patients have been found defective in leptin production or producing or producing ineffective leptin. Human obesity might be connected to a defect of leptin receptor or to its altered signal transduction. Leptin administration is therefore not important in human obesity treatment.
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PMID:[Leptin--the key to obesity?]. 972 70

Leptin contributes to the regulation of thermogenesis. In rodents, sympathetic nerve activity efferent to interscapular brown adipose tissue (IBAT-SNA) is involved. On the basis of the hypotheses that 1) leptin acutely potentiates hypothermia-induced increases in IBAT-SNA; 2) this action of leptin is specific to IBAT-SNA, i.e., it does not occur with renal sympathetic nerve activity (R-SNA); and 3) this effect of leptin depends on intact and functional leptin receptors, we measured IBAT-SNA and R-SNA in anesthetized lean and diet-induced obese Sprague-Dawley and in obese Zucker rats, randomly assigned to low-dose leptin or vehicle. Before the start of leptin or vehicle and 5 min, 90 min, and 180 min after, hypothermia (30 degrees C) was induced. Compared with vehicle, leptin did not significantly alter baseline R-SNA or IBAT-SNA. In lean Sprague-Dawley rats, hypothermia-induced increases in IBAT-SNA were significantly augmented by leptin but not by vehicle. In obese Sprague-Dawley rats, leptin did not potentiate hypothermia-induced increases in IBAT-SNA. In Zucker rats, IBAT-SNA did not increase with hypothermia and leptin was not able to induce sympathoactivation with cooling. Changes in R-SNA during hypothermia were not significantly modified by leptin in either group. Thus, low-dose leptin, although not altering baseline SNA, acutely enhances hypothermia-induced sympathetic outflow to IBAT in lean rats. This effect is specific for thermogenic SNA because leptin does not significantly alter the response of R-SNA to hypothermia. The effect depends on intact and functional leptin receptors because it occurs neither in rats with a leptin receptor defect nor in rats with acquired leptin resistance.
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PMID:Leptin potentiates thermogenic sympathetic responses to hypothermia: a receptor-mediated effect. 1214 55

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

Restricting energy expenditure is an adaptive response to food shortage. Despite being insulated with massive amount of fat tissues, leptin-deficient mice lose the ability to maintain their body temperature and develop deep hypothermia, which can be suppressed by exogenous leptin, suggesting an important role for leptin in energy expenditure regulation. However, the mechanism underlying the leptin action is not clear. We generated mice with disruption of glutamate release from leptin receptor-expressing neurons by deleting vesicular glutamate transporter 2 in these neurons, and found that these mice developed mild obesity purely due to reduced energy expenditure, exhibited bouts of rapidly reduced energy expenditure, body temperature and locomotion. In addition, these mice exhibited lower energy expenditure and body temperature in response to fasting and were defective in leptin-mediated thermogenic action in brown adipose tissues. Taken together, our results identify a role for glutamate release in mediating leptin action on energy expenditure.
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PMID:Glutamate release mediates leptin action on energy expenditure. 2419 56