Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Mahogany/Attractin gene (Atrn) has been proposed as a downstream mediator of Agouti signaling because yellow hair color and obesity in lethal yellow (A(y)) mice are suppressed by the mahogany (Atrn(mg)) mutation. The present study examined the distribution of Atrn mRNA in the brain and spinal cord by in situ hybridization. Atrn mRNA was found widely distributed throughout the central nervous system, with high levels in regions of the olfactory system, some limbic structures, regions of the brainstem, cerebellum and spinal cord. In the hypothalamus, Atrn mRNA was found in specific nuclei including the suprachiasmatic nucleus, the supraoptic nucleus, the medial preoptic nucleus, the paraventricular hypothalamic nucleus, the ventromedial hypothalamic nucleus, and the arcuate nucleus. These results suggest a broad spectrum of physiological functions for the Atrn gene product.
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PMID:Distribution of Mahogany/Attractin mRNA in the rat central nervous system. 1058 Jan

The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.
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PMID:Food-related sensory stimuli are able to promote pancreatic polypeptide elevation without evident cephalic phase insulin secretion in human obesity. 1089 54

Food intake is a regulated system. Afferent signals provide information to the central nervous system, which is the centre for the control of satiety or food seeking. Such signals can begin even before food is ingested through visual, auditory and olfactory stimuli. One of the recent interesting findings is the demonstration that there are selective fatty acid taste receptors on the tongue of rodents. The suppression of food intake by essential fatty acids infused into the stomach and the suppression of electrical signals in taste buds reflect activation of a K rectifier channel (K 1.5). In animals that become fat eating a high-fat diet the suppression of this current by linoleic acid is less than that in animals that are resistant to obesity induced by dietary fat. Inhibition of fatty acid oxidation with either mercaptoacetate (which blocks acetyl-CoA dehydrogenase) or methylpalmoxirate will increase food intake. When animals have a choice of food, mercaptoacetate stimulates the intake of protein and carbohydrate, but not fat. Afferent gut signals also signal satiety. The first of these gut signals to be identified was cholecystokinin (CCK). When CCK acts on CCK-A receptors in the gastrointestinal tract, food intake is suppressed. These signals are transmitted by the vagus nerve to the nucleus tractus solitarius and thence to higher centres including the lateral parabrachial nucleus, amygdala, and other sites. Rats that lack the CCK-A receptor become obese, but transgenic mice lacking CCK-A receptors do not become obese. CCK inhibits food intake in human subjects. Enterostatin, the pentapeptide produced when pancreatic colipase is cleaved in the gut, has been shown to reduce food intake. This peptide differs in its action from CCK by selectively reducing fat intake. Enterostatin reduces hunger ratings in human subjects. Bombesin and its human analogue, gastrin inhibitory peptide (also gastrin-insulin peptide), reduce food intake in obese and lean subjects. Animals lacking bombesin-3 receptor become obese, suggesting that this peptide may also be important. Circulating glucose concentrations show a dip before the onset of most meals in human subjects and rodents. When the glucose dip is prevented, the next meal is delayed. The dip in glucose is preceded by a rise in insulin, and stimulating insulin release will decrease circulating glucose and lead to food intake. Pyruvate and lactate inhibit food intake differently in animals that become obese compared with lean animals. Leptin released from fat cells is an important peripheral signal from fat stores which modulates food intake. Leptin deficiency or leptin receptor defects produce massive obesity. This peptide signals a variety of central mechanisms by acting on receptors in the arcuate nucleus and hypothalamus. Pancreatic hormones including glucagon, amylin and pancreatic polypeptide reduce food intake. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte-stimulating hormone, growth hormone and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides that modulate feeding. beta-Casomorphin, a heptapeptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group, including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines and thyrotropin-releasing hormone, all decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors that relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.
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PMID:Afferent signals regulating food intake. 1099 53

The tubby gene family consists of four members, TUB, TULP1, TULP2 and TULP3, with unknown function. However, a splice junction mutation within the mouse tub gene leads to retinal and cochlear degeneration, as well as maturity onset obesity and insulin resistance. Mutations within human TULP1 have also been shown to co-segregate in several cases of autosomal recessive retinitis pigmentosa (RP) and TULP1 deficiency in mice leads to retinal degeneration. The primary amino acid sequences of the tubby family members do not predict a likely biochemical function. As a first step in defining their function, we present a detailed characterization of the cellular and subcellular localization of the human (TUB) and mouse (tub) homologous gene products. We report the isolation of TUB splice variants which have different subcellular localizations (nuclear versus cytoplasmic) and which define a nuclear localization signal. In addition, using green fluorescent protein (GFP) tags, we observe a nuclear localization for TULP1, similar to TUB splicing forms TUB 561 and TUB 506. Finally, we report tubby expression in mouse brain by in situ hybridization and by immunohistochemistry with polyclonal antibodies. Protein was found in both the hypothalamic satiety centers and in a variety of other CNS structures including the cortex, cerebellum, olfactory bulb and hippocampus. Both nuclear and cytoplasmic signals were detected with a series of independently generated polyclonal antibodies, consistent with the presence of multiple alternatively spliced isoforms within the CNS.
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PMID:GFP-tagged expression and immunohistochemical studies to determine the subcellular localization of the tubby gene family members. 1100 Apr 83

In 30 children, aged 10-16 years and suffering from simple obesity, significantly lowered odour detection thresholds were noted. The thresholds were lower than the average for a given age group in around 20% of obese children in cases of odours stimulating olfactory nerve and in around 57% in cases of substances stimulating olfactory and trigeminal nerves. Odour identification thresholds were similarly affected, with identification of olfactory nerve plus trigeminal nerve stimulating odours affected more than twice as frequently. In 77% cases also the electrogustometric thresholds were found below the normal range values when anode was used as the stimulating electrode. The detected alterations may be linked to metabolic disturbances, which accompany simple obesity.
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PMID:Smell and taste in children with simple obesity. 1103 76

Distribution of glucose transporter (GLUT-1) in the microvascular endothelium of scrapie-infected SJL/J hyperglycemic mice showing clinical signs of scrapie, obesity and reduced glucose tolerance was studied in five brain regions: cerebral cortex, hippocampus, thalamus, cerebellum and olfactory bulb. Uninfected normoglycemic SJL/J mice showing normal glucose tolerance were used as a control. Ultrathin sections of brain samples embedded at low temperature in the hydrophilic resin Lowicryl K4M were exposed to anti-GLUT-1 antiserum followed by gold-labeled secondary antibodies. Labeling density was recorded over luminal and abluminal plasma membranes of microvascular endothelial cells. Ultrastructural observations revealed attenuation of the microvascular endothelial lining in numerous vascular profiles from brain samples of diabetic mice. Morphometric analysis revealed significant decreases of the labeling density for GLUT-1 in the microvasculature of the thalamus, cerebellum and, to a lesser degree, the hippocampus of diabetic mice. No significant differences between diabetic and non-diabetic, control mice were observed in the microvessels supplying cerebral cortex and olfactory bulb. These findings suggest that abnormal glucose metabolism, manifested by reduced glucose tolerance and hyperglycemia, leads to impaired transvascular glucose transport in some brain regions but not in others, presumably disturbing the function of those brain regions supplied by the affected blood microvessels.
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PMID:Quantitative immunogold study of glucose transporter (GLUT-1) in five brain regions of scrapie-infected mice showing obesity and reduced glucose tolerance. 1158 53

Tubby is a mouse gene that may provide a model for adult-onset obesity in humans. It is a member of a four gene family in mammals that collectively encode the Tubby-like proteins (TULPs), putative transcription factors which share similar 260 amino acid 'tubby domains' at their C-termini. The mammalian genome also encodes distant relatives of TULPs, which have been called TUSPs (tubby domain superfamily proteins). We have characterized the transcription unit of the single Drosophila TULP homolog, analyzed the expression pattern of the Drosophila TULP and TUSP genes, and determined the evolutionary relationships between the Drosophila proteins and members of the tubby domain superfamily in other organisms. Interestingly, like its mammalian homologs, Drosophila TULP is principally expressed in the embryonic central and peripheral nervous systems. This suggests that mammalian and Drosophila TULPs may possess some conserved functional properties in the nervous system. The Drosophila TUSP gene is also expressed in the central nervous system and olfactory organ but in few other peripheral sensory organs.
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PMID:Structure and expression patterns of Drosophila TULP and TUSP, members of the tubby-like gene family. 1220 60

The peroxisome proliferator activated receptor coactivator 1 alpha (PGC-1alpha) is a nuclear transcriptional coactivator that is expressed in brown adipose tissue, brain, heart and kidney as well as cold-exposed skeletal muscle. In liver, white and brown adipose tissue, PGC-1alpha expression is regulated in a manner suggesting a role in energy homeostasis. To characterize PGC-1alpha expression in the rodent brain and to determine brain PGC-1alpha regulation, we used in situ hybridization histochemistry in C57Bl/6J mice and Sprague-Dawley rats. We found that PGC-1alpha is widely expressed in brain areas, including in the olfactory bulb, cerebral cortex, the diagonal band of Broca, the medial septal nucleus, reticular thalamic nucleus, the striatum and globus pallidus, the hippocampus, the substantia nigra, the mesencephalic nucleus of the trigeminal nerve, the cochlear nucleus and the superior olivary complex. In contrast, PGC-1alpha expression was absent in the hypothalamus. To evaluate PGC-1alpha expression under different physiologic states in these various brain areas, we examined expression with fasting, leptin treatment and cold exposure (4 h at 4 degrees C) and found no change, nor was expression changed in the brain of the leptin-deficient ob/ob mice and the hyperleptinemic UCP-DTA mice. Hence, PGC-1alpha is widely expressed in the rodent brain, but is not regulated by states of caloric deficiency, leptin, obesity or cold exposure. Its functional role in the brain requires further study.
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PMID:Characterization of the peroxisome proliferator activated receptor coactivator 1 alpha (PGC 1alpha) expression in the murine brain. 1253 92

Insulin and its receptor are found throughout the central nervous system (CNS). Insulin administered into the CNS can exert powerful effects, yet the consensus is that little or no insulin is produced in the CNS. Therefore, CNS insulin is essentially dependent on the ability of peripheral insulin to cross the blood-brain barrier (BBB). Insulin is known to cross the BBB by a saturable transport mechanism. This transporter shows some thematic similarities to other transporters for peptides or regulatory proteins. It is unevenly distributed throughout the CNS with the olfactory bulbs having the fastest transport rate of any brain region. It is partially saturated at euglycemic levels, suggesting that its main signaling function occurs at physiological blood levels, rather than as a brake to hypoglycemic events. One probable function of the BBB transporter is to allow CNS insulin to act as a counter-regulatory hormone to peripheral insulin. The transporter is regulated, with the transport rate of insulin being altered during development and by fasting, obesity, hibernation, diabetes mellitus and Alzheimer's disease. Enhancement of insulin transport by lipopolysaccharide could be the basis for the insulin resistance seen with bacterial infections. Inhibition of insulin transport across the BBB by dexamethasone could be the basis for the enhanced appetite seen with glucocorticoid treatments. Insulin itself also has effects on the BBB, altering enzymatic and transporter functions. Overall, BBB transport of insulin provides a mechanism for peripheral insulin to act within the CNS as a regulatory peptide.
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PMID:The source of cerebral insulin. 1509 69

The present study examined the levels of 5-HT(2A) and 5-HT(2C) (2A and 2C receptors of 5-hydroxytryptamine; serotonin) receptor messenger RNA (mRNA) expressions in the brain of chronic high-fat diet-induced obese (DIO) and obese-resistant (DR) mice. Thirty-one mice were used in this study. Twenty-four mice were fed with a high-fat diet (HF: 40% of calories from fat) for 4 weeks and then classified as the DIO (n = 8) or DR (n = 8) mice according to the highest and lowest body weight (BW) gainers. Seven mice were placed on a low-fat diet (LF: 10% of calories from fat) and were used as controls. After 20 weeks of feeding, the visceral fat accumulation was 620 +/- 42 mg in the DIO group versus 198 +/- 89 mg in the DR and 84 +/- 18 mg in the LF groups. Using quantitative in situ hybridization techniques, levels of 2A and 2C serotonin (5-HT) receptor mRNAs were measured in multiple brain sections of mice from the three groups. Most regions did not differ between groups but, importantly, the DIO mice had a significantly higher level of 5-HT(2A) receptor mRNA expression in the olfactory nucleus (Olf) compared to the DR and LF mice (+30% and +37%, respectively). The levels of Olf 5-HT(2A) receptor mRNA expression were related to body fat mass. The level of 5-HT(2C) mRNA receptor expression in the ventromedial hypothalamic (VMH) nucleus was 40% higher in the DIO mice than in the LF mice. Furthermore, the 5-HT(2C) receptor mRNA expression in the posterodorsal part of the medial amygdaloid (MePD) nucleus was 25% higher in the DIO mice than in the DR mice. The level of VMH 5-HT(2C) receptor mRNA expression was correlated with body fat mass. In conclusion, this study has demonstrated differentially regulated levels of the 5-HT(2A) and 5-HT(2C) receptor mRNA expressions in the specific brain regions of the DIO and DR mice. It provides neural anatomical bases that the 5-HT(2C) receptors positively influence satiety center (VMH) while the 5-HT(2A) receptor regulates olfactory sensory effects. The findings also assist us to understand the role of these receptors in mice susceptible or resistant to diet-induced obesity.
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PMID:Differential expression of 5-HT(2A) and 5-HT(2C) receptor mRNAs in mice prone, or resistant, to chronic high-fat diet-induced obesity. 1530 19


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