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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total deficiency in or resistance to the protein leptin causes severe obesity. As leptin levels rise with increasing adiposity in rodents and man, it is proposed to act as a negative feedback 'adipostatic signal' to brain centres controlling energy homeostasis, limiting obesity in times of nutritional abundance. Starvation is also a threat to homeostasis that triggers adaptive responses, but whether leptin plays a role in the physiology of starvation is unknown. Leptin concentration falls during starvation and totally leptin-deficient ob/ob mice have neuroendocrine abnormalities similar to those of starvation, suggesting that this may be the case. Here we show that preventing the starvation-induced fall in leptin with exogenous leptin substantially blunts the changes in gonadal, adrenal and thyroid axes in male mice, and prevents the starvation-induced delay in ovulation in female mice. In contrast, leptin repletion during this period of starvation has little or no effect on body weight, blood glucose or ketones. We propose that regulation of the neuroendocrine system during starvation could be the main physiological role of leptin.
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PMID:Role of leptin in the neuroendocrine response to fasting. 871 38

We have observed seven initially obese individuals who, during the course of a strenuous weight-reduction program, developed diabetes mellitus: non-insulin-dependent diabetes mellitus in five cases and insulin-dependent diabetes mellitus in two cases. None had any sign of prior diabetic symptoms. Although weight reduction is encouraged in obesity, crash diets without proper medical surveillance may have deleterious effects. This sequence of induction of diabetes has not previously been reported in the medical literature. The metabolic situation in extremely low-calorie diets may be comparable to that in starvation. An attempt is made to explain our observation concerning the induction of a diabetic state during such diets, on the basis of increased insulin resistance in states of starvation and anorexia nervosa, with a concomitant role in stress hormones.
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PMID:Starvation diet and very-low-calorie diets may induce insulin resistance and overt diabetes mellitus. 877 29

Neuropeptide Y (NPY) neurones in the arcuate nucleus of the rodent hypothalamus may play a key role in responding to reductions in body energy stores with appropriate changes in energy homeostasis, namely an increase in food-seeking behaviour and hyperphagia, together with a reduction in heat production by brown adipose tissue. These adaptive responses are mimicked by the injection of NPY into the main sites of projection of the NPY neurones, and animals that are threatened by energy deficits (e.g. through starvation or insulin-deficient diabetes) show increased activity of these neurones. Genetically obese rodents also show hyperactivity of the NPY neurones, which is inappropriate to their energy needs and may contribute to their hyperphagia, reduced energy expenditure and excessive weight gain. The NPY neurones may be inhibited by insulin and leptin, which may both serve as signals of peripheral fat mass. Ultimately, characterization of the specific "feeding' receptors which mediate NPY's central effects on energy homeostasis may provide opportunities for designing drugs to manipulate and appetite and energy balance in man, notably obesity and the cachexia commonly associated with malignancy and chronic infection.
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PMID:Neuropeptide Y, the hypothalamus and the regulation of energy homeostasis. 887 Nov 82

Non-insulin-dependent diabetes mellitus (NIDDM) is one of the most common non-communicable diseases in the world. It has become obvious that NIDDM is the result of a collision between thrifty genes and an affluent society. Genes predisposing to NIDDM might have been survival genes for our ancestors, helping them to store energy during long periods of starvation. When these genes are exposed to a sedentary lifestyle and high caloric intake typical to the Western world, they predispose to obesity and insulin resistance. NIDDM results when beta cells cannot compensate for insulin resistance by increasing insulin secretion. Therefore, at least two inherited defects can be expected in NIDDM, one causing obesity and insulin resistance and the other inability to increase insulin secretion. In reality there may be more inherited defects. It has become quite clear that diabetes cannot simply be divided into NIDDM and insulin-dependent diabetes mellitus (IDDM). The disease is more heterogeneous; unmasking this heterogeneity and identifying new subgroups of diabetes presents a challenge to modern molecular biology.
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PMID:Non-insulin-dependent diabetes mellitus--a collision between thrifty genes and an affluent society. 907 23

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.
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PMID:[General anesthesia in Prader-Willi syndrome]. 910 80

The role of the microsomal ethanol-oxidizing system (MEOS) in hepatic ethanol metabolism is reviewed, with focus on its constitutive, ethanol-inducible cytochrome P-4502E1 (2E1). The MEOS was purified and reconstituted using 2E1, phospholipids, and cytochrome P-450 reductase and shown to oxidize ethanol to acetaldehyde, mainly as a monooxygenase and secondarily via hydroxyl radicals, with transcriptional and posttranscriptional regulation. Polymorphism of 2E1 was recognized, and enzymology (including cofactors, role of lipids, inducers, and inhibitors) as well as cellular and tissue distribution were chartered. Physiological functions involve lipid metabolism and ketone utilization in starvation, obesity, and diabetes. The most significant role of 2E1 is its adaptive response to high blood ethanol levels with a corresponding acceleration of ethanol metabolism. The associated free radical production, however, contributes to liver injury in the alcoholic. Most importantly, 2E1 has a unique capacity to activate many xenobiotics (85 of which are listed) to hepatotoxic or carcinogenic products. Induction of 2E1 also results in enhanced production of acetaldehyde, a highly reactive and toxic metabolite. The proliferation of the endoplasmic reticulum associated with 2E1 induction is also accompanied by enhanced activity of other cytochrome P-450s, resulting in accelerated metabolism of, and tolerance to, other drugs, as well as increased degradation of retinol and its hepatic depletion. Some substrates and metabolites, however, are innocuous and may eventually be used as markers of heavy drinking. Recently discovered effective 2E1 inhibitors also have great therapeutic potential.
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PMID:Cytochrome P-4502E1: its physiological and pathological role. 911 22

Treatment with low dose methotrexate in rheumatoid arthritis is associated with serious side effects in about 5 per cent of cases (respiratory, haematological or infectious). The goal of a null risk seems unrealistic because of the idiosyncrasy of some of the risks and our poor understanding of others (enzymatic polymorphisms might be operational, and infectious agents could act as co-factors). However, risk can be greatly reduced by a careful selection of patients. Some contraindications are strict: poor compliance and the possibility of mistake in the timing of the administration; pregnancy or desire for pregnancy; treatment with trimetoprim; haemodialysis; renal insufficiency (clearance < or = 50 ml/min) (and therefore old age), alcoholism. Others remain relative although well established; hypoalbuminaemia, diabetes mellitus, obesity, past infection with hepatitis virus. Others are dubious: starvation, macrocytosis, surgical stress, NSAIDs. An extensive large study of side effects is warranted.
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PMID:[Treatment with low dose methotrexate in rheumatoid arthritis: risk factors for severe complications]. 923 4

The role of neuropeptide Y (NPY), leptin and 5-HT and other neurotransmitters implicated in the regulation of energy balance are only now being fully investigated. Little is known about how they may interact with each other in this complex process. In evolutionary terms, the availability of excess food, and the risk of obesity, is only a recent occurrence in humans. Man, and perhaps other species, may not have developed a specialised neurochemical system for adjusting food intake during obesity. Hence perturbation of a single system, such as hypothalamic NPY or leptin, is unlikely to be directly responsible for the development of most obesity. In contrast, periods of food deprivation and partial starvation have been common in the animal kingdom and the multitude of neurotransmitters implicated in energy balance are more likely to be directed towards increasing food consumption and conserving energy than reducing appetite and increasing thermogenesis in the presence of excess. The last few years have witnessed rapid advances in the understanding of the fundamental mechanisms that regulate body weight and fat content. This progress will undoubtedly continue in the future, and it is hoped that this will be rewarded with the development of new drugs to treat obesity. At present, however, it is unclear whether NPY, leptin, or other apparently strong candidates will be the winner in the lucrative race for the ideal anti-obesity drug.
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PMID:Neurobiology. 924 37

Prematurity, maternal smoking, and low birth weight each result in neuroendocrine dysfunction and increased perinatal morbidity and mortality. Leptin, an adipocyte-secreted protein, has provided the first physiological link to the regulatory system controlling starvation-induced neuroendocrine changes in rodents. This study investigated whether leptin concentrations were detectable in cord blood of newborns, and assessed the effect of birth weight, prematurity, and maternal smoking on cord blood leptin concentrations. Fifty consecutively enrolled full-term and 12 preterm newborns born to mothers who smoked during pregnancy were compared to 50 full-term and 12 preterm newborns born to parents who were nonsmokers. RIA for leptin was performed using cord blood samples collected immediately after birth. Leptin concentrations were detectable in newborns and correlated positively with obesity (full-term, r = 0.30, P < 0.01; preterm, r = 0.47, P < 0.05). Maternal smoking during pregnancy was associated with decreased leptin concentrations in the cord blood of both full-term and preterm newborns. This effect was independent of obesity (full-term newborns: 5.25 +/- 2.48 vs. 4.21 +/- 2.71 ng/ml, P = 0.01) and was more pronounced in premature newborns (5.67 +/- 3.6 vs. 2.46 +/- 2.03, P = 0.02), and its magnitude in full-term newborns was directly related to the reported number of cigarettes the mothers of the full-term newborns smoked per day (r = -0.438, P < 0.001). Thus, low birth weight and maternal smoking are both associated with decreased leptin concentrations, and these effects are more pronounced in premature newborns. Future studies will be needed to determine whether administration of leptin might reverse the neuroendocrine dysfunction caused by maternal smoking.
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PMID:Effect of birth weight and maternal smoking on cord blood leptin concentrations of full-term and preterm newborns. 928 10

Mitochondrial uncoupling proteins (UCPs) are transporters that are important for thermogenesis. The net result of their activity is the exothermic movement of protons through the inner mitochondrial membrane, uncoupled from ATP synthesis. We have cloned a third member of the UCP family, UCP3. UCP3 is expressed at high levels in muscle and rodent brown adipose tissue. Overexpression in yeast reduced the mitochondrial membrane potential, showing that UCP3 is a functional uncoupling protein. UCP3 RNA levels are regulated by hormonal and dietary manipulations. In contrast, levels of UCP2, a widely expressed UCP family member, showed little hormonal regulation. In particular, muscle UCP3 levels were decreased 3-fold in hypothyroid rats and increased 6-fold in hyperthyroid rats. Thus UCP3 is a strong candidate to explain the effects of thyroid hormone on thermogenesis. White adipose UCP3 levels were greatly increased by treatment with the beta3-adrenergic agonist, CL214613, suggesting another pathway for increasing thermogenesis. UCP3 mRNA levels were also regulated by dexamethasone, leptin, and starvation, albeit differently in muscle and brown adipose tissue. Starvation caused increased muscle and decreased BAT UCP3, suggesting that muscle assumes a larger role in thermoregulation during starvation. The UCP3 gene is located close to that encoding UCP2, in a chromosomal region implicated in previous linkage studies as contributing to obesity.
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PMID:Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. 930 58


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