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)

We report robust HPLC/UV methods for quantifying retinyl esters (RE), retinol (ROL), and retinal (RAL) applicable to diverse biological samples with lower limits of detection of 0.7, 0.2, and 0.2 pmol, respectively, and linear ranges greater than 3 orders of magnitude. These assays function well with small, complex biological samples (10-20mg tissue). Coefficients of variation range from 5.9 to 10.0% (intraday) and from 5.9 to 11.0% (interday). Quantification of endogenous RE, ROL, and RAL in mouse serum and tissues (liver, kidney, adipose, muscle, spleen, testis, skin, brain, and brain regions) reveals utility. Ability to discriminate spatial concentrations of ROL and RE is illustrated with C57BL/6 mouse brain loci (hippocampus, cortex, olfactory bulb, thalamus, cerebellum, and striatum). We also developed a method to distinguish isomeric forms of ROL to investigate precursors of retinoic acid. The ROL isomer assay has limits of detection between 3.5 and 4.5 pmol and has a linear range and coefficient of variation similar to those of the ROL/RE and RAL assays. The assays described here provide for sensitive and rigorous quantification of endogenous RE, ROL, and RAL to elucidate retinoid homeostasis in disease states such as Alzheimer's disease, type 2 diabetes, obesity, and cancer.
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PMID:HPLC/UV quantitation of retinal, retinol, and retinyl esters in serum and tissues. 1841 Jul 39

The cannabinoid CB1 receptor has been implicated in the regulation of appetite and the consumption of palatable foods. This experiment aimed to explore the involvement of the CB1 receptor in the early and late stages of high fat diet-induced obesity in C57BL/6 mice. The C57Bl/6 mice were placed on a high fat (HF) or low fat/high carbohydrate (LF) diet for 3 or 20 weeks. Quantitative autoradiography revealed that binding of [3H] CP-55,940 (CB1 receptor ligand) was elevated following 3 weeks of HF feeding in areas including the medial/ventral anterior olfactory nucleus (22.1%), agranular insular cortex (24.0%) and the hypothalamus (31.5%) compared to LF controls. This increased level of binding was correlated with an increase in plasma leptin in the hypothalamus, raising the possibility that this hormone may exert inhibitory control over endocannabinoid signalling at this stage of obesity. Mice fed a HF diet for 20 weeks were obese, hyperphagic and had decreased CB1 receptor binding levels in the substantia nigra (12.8%) and ventral tegmental area (17.1%) compared to LF controls. The low [3H] CP-55,940 binding density seen in these reward-related areas in the late stage of obesity may be indicative of increased endocannabinoid release due to the chronic HF diet consumption.
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PMID:Temporal and site-specific brain alterations in CB1 receptor binding in high fat diet-induced obesity in C57Bl/6 mice. 1875 50

AdipoR1 and AdipoR2 are receptors for the adipocyte-derived hormone adiponectin, which is an important regulator of glucose and lipid metabolism, and which has also been implicated in the control of food intake and energy homeostasis. In the present study, we have demonstrated that AdipoR1 is expressed in mature sensory neurons of the olfactory mucosa of mice, in a pattern reminiscent of the olfactory marker protein. AdipoR1 expression levels in the olfactory mucosa have been observed to increase gradually during late embryogenesis until adulthood. No local expression of adiponectin has been detected in nasal tissues, indicating that serum adiponectin is the ligand for AdipoR1 in olfactory sensory neurons. As the serum adiponectin concentration is regulated depending on adipose tissue mass, with a reduction of adiponectin levels being seen in obesity, AdipoR1 function in the olfactory epithelium seems to be directly linked to the nutritional status of the body, suggesting a potential modulatory role for AdipoR1 in the adjustment of the olfactory system to energy balance requirements.
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PMID:Expression of adiponectin receptor 1 in olfactory mucosa of mice. 1879 42

Epigenetic influences on the fetus's genotype have been shown to occur during intrauterine life. Experimentally imposed extracellular dehydration in pregnant rats (a model for human hyponatremia caused by gravidic vomiting) brings about a dramatic enhancement of salt appetite not only in the dam, but also in offspring when they reach adulthood. This phenomenon has been verified in human newborn infants and adults whose mothers experienced nausea and/or vomiting during pregnancy. Alcohol consumption during pregnancy enhances its palatability for the offspring. Ingestion of olfactory test substances like anise or carrot by the mother during pregnancy gives rise to a preference for the same testants in the offspring. Under- or overnutrition in the pregnant mother appears to play a role in reprogramming the postnatal regulation of both feeding and fat reserves in offspring. Both maternal under- and overnutrition during pregnancy predispose the offspring to later development of obesity and type 2 diabetes mellitus. A careful examination of the systems concerned with the regulation of food intake, and the neurosubstances involved in such regulation, reveals some of the mechanisms by which maternal nutritional status can affect the offspring and their food-related behaviors.
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PMID:Prenatal imprinting of postnatal specific appetites and feeding behavior. 1880 61

Obesity is recognized as a worldwide health problem. Overconsumption of fatty foods contributes significantly to this phenomenon. Rodents, like humans, display preferences for lipid-rich foods. Rodents thus provide useful models to explore the mechanisms responsible for this complex feeding behavior resulting from the integration of multiple oral and postoral signals. Over the last decades, the lipid-mediated regulation of food intake has received considerable attention. By contrast, orosensory lipid perception was long thought to involve only textural and olfactory cues. Recent findings have challenged this limited viewpoint. These recent data strongly suggest that the sense of taste also plays significant roles in the spontaneous preference for fatty foods. This paper provides a brief overview of postoral regulation of food intake by lipids and then highlights recent data suggesting the existence of a "fatty taste" which might contribute to lipid overeating and hence to the risk of obesity.
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PMID:Molecular mechanisms of fat preference and overeating. 1899 57

Obesity constitutes a major public health problem for the twenty-first century, with its epidemic spread worldwide, particularly in children. The overconsumption of fatty foods greatly contributes to this phenomenon. Rodents and humans display a spontaneous preference for lipid-rich foods. However, the molecular mechanisms underlying this pattern of eating behaviour in mammals remain unclear. The orosensory perception of dietary lipids was long thought to involve only textural and olfactory cues. Recent findings challenge this limited viewpoint, strongly suggesting that the sense of taste also plays a significant role in dietary lipid perception and might therefore be involved in the preference for fatty foods and obesity. This minireview analyses recent data relating to the molecular mechanisms and physiological consequences of this means of orosensory lipid perception.
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PMID:Orosensory perception of dietary lipids in mammals. 1908 26

The role of insulin pathways in olfaction is of significant interest with the widespread pathology of diabetes mellitus and its associated metabolic and neuronal comorbidities. The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and postsynaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made prediabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors.
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PMID:Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors. 1945 42

Could the mere perception of food availability reverse the beneficial effects of diet restriction, which robustly increases lifespan and reduces aging-related disease in many species? We had noted from previous work in Drosophila that the effects of dietary restriction were fast acting, completely reversible, and largely independent of the energetic content of the food. Indeed, some characteristic of the diet seemed to be "sensed" by the flies independent of their tendency to eat it. We quickly realized that the Drosophila olfactory system, with its well-understood architecture and associated set of genetic tools, was the ideal model to test our hypothesis. Subsequent work resulted in the identification of particular odorants and populations of sensory neurons with potent effects on lifespan, obesity, and metabolism.
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PMID:The modulation of lifespan by perceptual systems. 1968 14

A major problem in the dietary treatment of disorders associated with excessive eating, such as obesity, is the high rate of relapse into maladaptive eating habits after withdrawal from consumption of palatable, energy-dense food. As olfaction has a major role in appetite and eating behavior, in this study we used a reinstatement model based on conditioned place preference to investigate the ability of olfactory priming to reinstate extinguished chocolate-induced conditioned place preference in sated mice. We found that olfactory priming, which was ineffective in inducing conditioned place preference in the control group, reactivated place preference following the extinction procedure in the experimental group. These results extend previous reports of the reinstatement of food seeking induced by pellet priming and, for the first time, show the possibility of using olfactory priming in an animal model of relapse. In light of the major role of olfactory inputs in appetite and of cues in relapse, the present results indicate that smell is an important factor to consider in the treatment of eating disorders.
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PMID:Olfactory priming reinstates extinguished chocolate-induced conditioned place preference. 2000 61

Mutations in the prokineticin 2 peptide (PROK2) and its seven-transmembrane domain type 2 receptor PROKR2 are newly identified molecular culprits in autosomal Kallmann syndrome (KS). Prok2 and prokr2 gene knockout mice both have agenesis or hypoplasia of the olfactory bulbs, associated with hypogonadotropic hypogonadism linked to abnormal GnRH neuron migration. Prok2-/- and prokr2-/- mice are the first murine models of this human disease. KS patients of both sexes have a variety of point mutations, missense mutations, frameshifts and nonsense mutations in the PROK2 and PROKR2 genes that lead to a loss of peptide or receptor function. When only one allele is affected, penetrance of the two main clinical features of KS may be incomplete: subjects with only one mutant allele may have (1) no symptoms, with normal olfaction and complete pubertal development, (2) congenital isolated (idiopathic) hypogonadotropic hypogonadism (IHH) but normal olfaction, (3) anosmia/hyposmia but normal pubertal development and gonadal function or (4) the two cardinal clinical KS signs, anosmia and IHH. These phenotypic dissociations can be seen in family members with the same PROK2/PROKR2 mutations. By contrast, patients with two mutant alleles almost always have the cardinal signs of KS. Even when monoallelic PROK2/PROKR2 mutations are associated with full-blown KS, the reproductive phenotype in males is less severe than in KS associated with biallelic mutations, evidenced by significantly lower frequency of cryptorchidism and micropenis, greater testicular volume, and higher serum levels of LH, FSH and testosterone. Moreover, at least some of these monoallelic cases are in fact digenic, in that they also carry mutations of other KS/IHH genes. Overall, these observations point towards a combination of mendelian autosomal recessive transmission, with more complex oligogenic transmission. Patients with this genetic form of KS have been reported to have a possible increased prevalence of obesity and sleep disorders, which may be related to the role of PROK2 and PROKR2 in food intake and circadian rhythms. However, diurnal variation of serum cortisol levels appears to be physiologically maintained.
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PMID:Kallmann syndrome caused by mutations in the PROK2 and PROKR2 genes: pathophysiology and genotype-phenotype correlations. 2038 90


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