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

Expression of the diabetes ( db/db) genotype mutation in female C57BL/KsJ mice induces a complex diabetes-obesity syndrome (DOS) responsible for reproductive tract involution promoted by hypercytolipidemia (HCL). Current studies define the complex and influences of the endometabolic variables that promote reproductive tract involution at the time of initial db/db mutation expression onset in female C57BL/KsJ mice. Littermate-paired, normal ( +/?) and db/db groups were isolated between 2 - 4 weeks of age and tissue samples analyzed for utero-ovarian alterations induced by the systemic, tissue, cellular and structural consequences of mutation expression. Significantly elevated body weights, blood glucose concentrations and serum insulin levels contrasted with atrophic utero-ovarian indices in db/db mutants compared to +/? groups. The onset of the db/db-expression promoted obesity and a mild hyperglycemic-hyperinsulinemic state. Initial db/db expression was characterized by significantly increased utero-ovarian insulin binding without variation in membrane insulin receptor concentrations. However, significant elevations in tissue glucose sequestration rates, norepinephrine (NE) concentrations and triacylglyceride lipase activity in db/db groups indicated that a complex of endometabolic counter-regulatory influences promoted the metabolic shunting of excess glucose and triglyceride moieties towards hypercytolipidemic storage. The resulting DOS-promoted accumulation of utero-ovarian cytolipidemic pools compromised reproductive tract cytoarchitecture in db/db mice. The results of these studies indicate that the inability of utero-ovarian tissue compartments to exhibit metabolic adaptation to the enhanced availability, transport and cellular imbibition of extracellular glucose-lipid pools promotes the initial cellular compromise recognized to induce reproductive failure in db/db mutants.
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PMID:Variable onset determinants and consequences of diabetes (db/db) obesity mutation expression: adrenergic promotion of utero-ovarian dysfunction. 1515 12

Background: The diabetes (db/db) mutation induces a hyperglycemic-hyperinsulinemic endometabolic environment that promotes hypercytolipidemic, utero-ovarian involution in C57BL/KsJ mice, resulting in reproductive sterility and eventual organoatrophy. Objective: Evaluation of the effectiveness of progesterone therapy (P-HRx), initiated prior to the genetic expression of the overt diabetes-obesity syndrome (DOS), on moderating the severity of female reproductive tract involution promoted by db/db mutation expression was evaluated by analysis of cytoarchitectural, endocrine and tissue lipo-metabolic indices relative to oil (O)-vehicle-treated (HRx) control (+/?) and db/db groups. Experimental design: All HRx treatments were started at 4 weeks of age (pre-overt DOS stage) and continued through 16 weeks of age (chronic DOS expression) when tissue and cellular endometabolic parameters were evaluated. Results: The DOS induced a dramatic increase in phenotypic obesity, hyperglycemia and hyperinsulinemia in db/db groups, relative to +/?, throughout the experimental period. In contrast, utero-ovarian weights were dramatically reduced in db/db groups relative to +/? indices. Chronic P-HRx effectively reversed these DOS-induced trends in db/db groups, maintaining moderated body and tissue weights, as well as re-establishing normal insulin indices, under a persistent hyperglycemic condition. In addition, P-HRx moderated the dramatic hypercytolipidemic condition which promotes utero-ovarian involution in db/db mice as evidenced by the reduction in observed tissue cytolipidemia. The concurrent normalization of tissue lipase and enhancement of glucose utilization indices by db/db utero-ovarian compartments, under moderated insulin recognition parameters, indicated that P-HRx effectively suppressed the severity of both the structural and endometabolic consequences of the DOS in db/db groups, without restraining hyperglycemic conditions. Conclusion: These results indicate that the pathophysiological alterations induced by the db/db mutation may be modulated through low-dose steroidal therapy, the efficacy of which is suspected to occur by the augmentation of normal insulin-coupled, post-receptor directed glucose utilization via the stimulation of oxidative metabolic pathways capable of maintaining normal utero-ovarian structural continuity and metabolic homeostasis.
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PMID:Hypercytolipidemia promotes diabetes (db/db) mutation-associated utero-ovarian involution: counter-regulatory influences of progesterone. 1517 15

The diabetes (db/db) mutation (leptin-receptor defect) induces a hyperglycemic-hyperinsulinemic endometabolic environment that promotes hypercytolipidemic, utero-ovarian involution in C57BL/KsJ mice, resulting in reproductive sterility and eventual organoatrophy. The effectiveness of low-dose, 17-B-estradiol therapy (E2-HRx), initiated prior to the genetic expression of the overt diabetes-obesity syndrome (DOS) on preventing female reproductive tract involution was evaluated by analysis of cytochemical, endocrine and tissue lipo-metabolic indices relative to oil (O)-vehicle treated (HRx) control (+/?) and (db/db) groups. All HRx treatments started at 4 weeks of age (i.e., pre-overt DOS stage) and continued through 16 weeks of age (i.e., chronic DOS expression) when tissue parameters were evaluated. The DOS promoted a dramatic increase in phenotypic obesity, hyperglycemia and hyperinsulinemia in (db/db) groups, relative to (+/?) indices, throughout the experimental period. In contrast, utero-ovarian weights were dramatically reduced in (db/db) groups relative to (+/?). Chronic low-dose E2-HRx moderated these DOS-induced trends in (db/db) groups, maintaining lowered body weights and normoglycemic parameters while stimulating utero-ovarian weight indices. In addition, E2-HRx prevented the dramatic hypercytolipidemic condition which promotes utero-ovarian involution in (db/db) mice as evidenced by the maintenance of normal reproductive cytoarchitecture. The concurrent moderation of tissue lipase activity and stimulated glucose uptake rates by (db/db) utero-ovarian compartments, under persistent hyperinsulinemic influences, indicated that E2-HRx effectively reduced both the structural and endometabolic consequences of the DOS from promoting (db/db)-associated reproductive organoatrophy. These results indicate that the pathophysiological alterations induced by the (db/db) mutation may be ameliorated through low-dose steroidal therapy, the efficacy of which is suspected to occur via membrane metabolic cascade induction mechanisms or by direct nuclear transcription modulation in reproductive target cells. The subsequent re-establishment of insulin-coupled glucose utilization and suppressed caloric shunting towards lipogenesis promotes the normalization of utero-ovarian structural and metabolic homeostasis in C57BL/KsJ-db/db mutants.
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PMID:Diabetes (db/db) mutation-induced female reproductive tract hypercytolipidemia: estrogenic restoration of utero-ovarian indices. 1521 26

Various methods have been applied for the enzymatic preparation of diacylglycerols that are used as dietary oils for weight reduction in obesity and related disorders. Interesterification of rapeseed oil triacylglycerols with commercial preparations of monoacylglycerols, such as Monomuls 90-O18, Mulgaprime 90, and Nutrisoft 55, catalyzed by immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) in vacuo at 60 degrees C led to extensive (from 60 to 75%) formation of diacylglycerols. Esterification of rapeseed oil fatty acids with Nutrisoft, catalyzed by Lipozyme RM in vacuo at 60 degrees C, also led to extensive (from 60 to 70%) formation of diacylglycerols. Esterification of rapeseed oil fatty acids with glycerol in vacuo at 60 degrees C, catalyzed by Lipozyme RM and lipases from Thermomyces lanuginosus (Lipozyme TL IM) and Candida antarctica (lipase B, Novozym 435), also provided diacylglycerols, however, to a lower extent (40-45%). Glycerolysis of rapeseed oil triacylglycerols with glycerol in vacuo at 60 degrees C, catalyzed by Lipozyme TL and Novozym 435, led to diacylglycerols to the extent of </=50%. Repeated use of Lipozyme RM in the esterification of rapeseed oil fatty acids with Monomuls resulted in minor reduction of its activity. The products of esterification of rapeseed oil fatty acids with Monomuls and glycerol yielded upon short-path vacuum distillation residues (diacylglycerol oils) containing 66-70% diacylglycerols.
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PMID:Solvent-free lipase-catalyzed preparation of diacylglycerols. 1531 68

We have used rat cDNA microarrays to identify adipocyte-specific genes that could play an important role in adipocyte differentiation or function. Here, we report the cloning and identification of a 2.0-kb mRNA coding for a putative protein that we have designated as desnutrin. The novel gene is expressed predominantly in adipose tissue, and its expression is induced early during 3T3-L1 adipocyte differentiation. Desnutrin mRNA levels were regulated by the nutritional status of animals, being transiently induced during fasting. In vitro desnutrin gene expression was up-regulated by dexamethasone in a dose-dependent manner but not by cAMP, suggesting that glucocorticoids could mediate the increase in desnutrin mRNA levels observed during fasting. Desnutrin mRNA codes for a 486-amino acid putative protein containing a patatin-like domain, characteristic of many plant acyl hydrolases belonging to the patatin family. Confocal microscopy of enhanced green fluorescent protein-tagged desnutrin protein-transfected cells showed that the fusion protein localized in the cytoplasm. Moreover, cells overexpressing desnutrin by transfection showed an increase in triglyceride hydrolysis. Interestingly, we also found that the desnutrin gene expression level was lower in ob/ob and db/db obese mouse models. Overall, our data suggest that the newly identified desnutrin gene codes for an adipocyte protein that may function as a lipase and play a role in the adaptive response to a low energy state, such as fasting, by providing fatty acids to other tissues for oxidation. In addition, decreased expression of desnutrin in obesity models suggests its possible contribution to the pathophysiology of obesity.
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PMID:Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. 1533 59

Public health efforts and current antiobesity agents have not controlled the increasing epidemic of obesity. Investigational antiobesity agents consist of 1) central nervous system agents that affect neurotransmitters or neural ion channels, including antidepressants (bupropion), selective serotonin 2c receptor agonists, antiseizure agents (topiramate, zonisamide), some dopamine antagonists, and cannabinoid-1 receptor antagonists (rimonabant); 2) leptin/insulin/central nervous system pathway agents, including leptin analogues, leptin transport and/or leptin receptor promoters, ciliary neurotrophic factor (Axokine), neuropeptide Y and agouti-related peptide antagonists, proopiomelanocortin and cocaine and amphetamine regulated transcript promoters, alpha-melanocyte-stimulating hormone analogues, melanocortin-4 receptor agonists, and agents that affect insulin metabolism/activity, which include protein-tyrosine phosphatase-1B inhibitors, peroxisome proliferator activated receptor-gamma receptor antagonists, short-acting bromocriptine (ergoset), somatostatin agonists (octreotide), and adiponectin; 3) gastrointestinal-neural pathway agents, including those that increase cholecystokinin activity, increase glucagon-like peptide-1 activity (extendin 4, liraglutide, dipeptidyl peptidase IV inhibitors), and increase protein YY3-36 activity and those that decrease ghrelin activity, as well as amylin analogues (pramlintide); 4) agents that may increase resting metabolic rate ("selective" beta-3 stimulators/agonist, uncoupling protein homologues, and thyroid receptor agonists); and 5) other more diverse agents, including melanin concentrating hormone antagonists, phytostanol analogues, functional oils, P57, amylase inhibitors, growth hormone fragments, synthetic analogues of dehydroepiandrosterone sulfate, antagonists of adipocyte 11B-hydroxysteroid dehydrogenase type 1 activity, corticotropin-releasing hormone agonists, inhibitors of fatty acid synthesis, carboxypeptidase inhibitors, indanones/indanols, aminosterols, and other gastrointestinal lipase inhibitors (ATL962). Finally, an emerging concept is that the development of antiobesity agents must not only reduce fat mass (adiposity) but must also correct fat dysfunction (adiposopathy).
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PMID:Current and investigational antiobesity agents and obesity therapeutic treatment targets. 1534 Jan

Adipose tissue is considered as the body's largest storage organ for energy in the form of triacylglycerols, which are mobilized through lipolysis process, to provide fuel to other organs and to deliver substrates to liver for gluconeogenesis (glycerol) and lipoprotein synthesis (free fatty acids). The release of glycerol and free fatty acids from human adipose tissue is mainly dependent on hormone-sensitive lipase which is intensively regulated by hormones and agents, such as insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). A special attention is paid to the recently discovered perilipins which could regulate the activity of the lipase hormono-sensible. Most of the plasma triacylglycerols are provided by dietary lipids, secreted from the intestine in the form of chylomicron or from the liver in the form of VLDL. Released into circulation as non-esterified fatty acids by lipoprotein lipase, those are taken up by adipose tissue via specific plasma fatty acid transporters (CD36, FATP, FABPpm) and used for triacylglycerol synthesis. A small part of triacylglycerols is synthesized into adipocytes from carbohydrates (lipogenesis) but its regulation is still debated in human. Physiological factors such as dieting/fasting regulate all these metabolic pathways, which are also modified in pathological conditions e.g. obesity.
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PMID:Metabolism of lipids in human white adipocyte. 1552 72

Gastrointestinal malignancies may be associated with obesity, defined specifically by increased body-mass index, and based largely on environmental factors rather than genetics. In particular, there seems to be a definite increase in the incidence of both oesophageal and colorectal cancer. Mechanisms associated with obesity include a particular metabolic state characterized by hyperinsulinemia, or insulin resistance, along with elevated serum leptin. Leptin is derived from adipocytes and appears to play a role in the regulation of ghrelin, a peptide derived from the stomach and small intestine that stimulates appetite and weight gain. In addition to these metabolic changes, there are other anatomical alterations that may indirectly predispose to cancer, including the predisposition of obesity to gastroesophageal reflux and, possibly, oesophageal cancer. Other mechanisms may involve adipocyte-derived cytokines, or adipokines, that may serve as signalling devices in the pathogenesis of cancer. Finally, pharmacologic and surgical avenues available for treatment of obesity, including lipase inhibitors and gastric or jejuno-ileal bypass procedures may set the stage for subsequent gastric or intestinal tract cancer.
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PMID:Risk of gastrointestinal malignancies and mechanisms of cancer development with obesity and its treatment. 1556 45

The overweight and obesity represent severe problems for the health management system of developed countries. In the evolution of obesity, beside genetic background, the environmental factors also play important roles. In the daily routine, the majority of obese patients need drug treatment, over the diet and physical activity. Among the available medicines the inhibitors of monoamine re-uptake causes dry mouth, tachycardia, sleeplessness and elevated blood pressure, therefore, due to the frequently associated obesity and hypertension many physicians avoid using these compounds. The orlistat as a selective inhibitor of pancreatic and enteral lipase enzymes impedes the absorption of the highest calorie containing nutrients, the fats exerting beneficial effects in the treatment of obesity. The abdominal bloating and diarrhea as side effects of the drug may act as an advantage in many cases, since these happen especially in those cases when the patient neglects the previously suggested low fat diet and therefore the drug induced diarrhea and bloating may mean a feed-back for the patient in respect of the proper diet. Recent studies show many beneficial biochemical changes in obesity related pathological metabolic processes during the administration of orlistat. The authors, in their present work review in short the role of orlistat in the treatment of slimming cure.
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PMID:[The role of orlistat in the treatment of obesity]. 1581 87

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and adipocyte gene expression in adipocytes. In this study, we have shown for the first time the gene expression profile in isolated rat adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The rat adipocytes were treated with 100 muM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. A total of 633 or 427 genes was up-regulated (>1.5-fold) by the treatment of adipocytes with C3G or Cy, respectively. The up-regulated genes include lipid metabolism and signal transduction-related genes, however, the altered genes were partly different between the C3G- and Cy-treated groups. Based on the gene expression profile, we demonstrated the up-regulation of hormone sensitive lipase and enhancement of the lipolytic activity by the treatment of adipocytes with C3G or Cy. These data have provided an overview of the gene expression profiles in adipocytes treated with anthocyanins and identified new responsive genes with potentially important functions in adipocytes related with obesity and diabetes that merit further investigation.
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PMID:Gene expression profile of isolated rat adipocytes treated with anthocyanins. 1586 61


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