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

1. When gastrointestinal transit and emptying of intraluminal contents were studied using a radioactive tracer marker [( 14C]PEG-4000), the fastest gastric transit and the slowest overall transit time were observed in female Wistar rats (1-3 months old) after they were fed a cafeteria diet (a hypercaloric diet). 2. The small intestine length of cafeteria fed rats was higher than lean rats, whereas the stomach and large bowel length showed no difference between cafeteria and lean rats. 3. A state of mild obesity was obtained after rats were fed a cafeteria diet. This obesity was demonstrated by the highest body weight and the highest gain of white adipose tissue in rats fed a cafeteria diet.
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PMID:Effect of cafeteria diet on the gastrointestinal transit and emptying in the rat. 167 3

Assuming that the serum-to-saliva transfer of insulin reflects internalization and re-cycling of the hormone in the membrane-located binding sites of salivary epithelial cells and that these cells have in obesity a'marked decrease in insulin receptor content, it has been postulated that insulin resistance in infantile obesity can be detected by the changes in the salivary immunoreactive insulin during the oral glucose tolerance test (OGTT). The study included 31 obese children and adolescents of both sexes, subjected to OGTT. Samples of blood and saliva were collected at 30, 60, 120, 180 and 240 minutes for determinations of glucose and IRI. The blood glucose values were generally normal whereas IRI was excessively high. The dynamics of salivary IRI was similar (easy peak followed by slow descent) with the mean serum values but lower by about two-thirds, and the peak was 30-60 minutes delayed. The serum IRI values correlated significantly with the saliva ones at all time-intervals except for the 30-minute ones. The serum IRI values were significantly lower at the 30-minute time interval, whereas the salivary IRI were the lowest (and of borderline significance) at the 60-min. time interval. The mean glucose/kg doses given orally were not significantly different in the two groups. It was concluded that a hormonal activity detectable by IRI assay through the PEG separation method does exist, with a concomitant variation of serum-to-saliva transfer as shown by the OGTT test. It was also concluded that since the salivary values are lower, the direction of the flow is from serum to saliva and not the reverse. Finally, on the basis of our data, an "in situ" synthesis of insulin (hormonogenic exocrinism) can not be ruled out.
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PMID:Serum-to-saliva transfer of the immunoreactive insulin (IRI) in children with obesity associated with insulin-resistance. 331 76

To learn about adipose differentiation of precursors from postnatal adipose tissue of lean and massively obese subjects, human omental adipocyte precursor-murine renal adenocarcinoma cell (RAG) hybrids were formed by fusion with polyethylene glycol, and cultured selectively with 50 microM ouabain in hypoxanthine aminopterin thymidine (HAT) medium. Under conditions in which the parent cells did not differentiate, a number of hybrids, which were cloned, revealed morphologic and biochemical evidence of differentiation. In addition to activation of human genes within the common nucleus of the hybrids, murine cytoplasmic activators are probably also involved because heterocaryons (fused cells with two interspecific nuclei) revealed the same phenomenon. Hybrids composed of precursors from massively obese subjects disclosed more frequent and prominent differentiation. Since these hybrids, in contrast to those from the lean, recapitulate this phenomenon in subcultures, they provide the potential system for mapping the human gene(s) responsible for adipose differentiation and its exaggeration in massive obesity.
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PMID:Exaggerated triglyceride accretion in human preadipocyte-murine renal line hybrids composed of cells from massively obese subjects. 336 10

There is increasing incidence of adenocarcinoma of the esophagastric junction (EGJ) especially in young white men (+35% in 30 years). The reasons for this are not yet well known, however one of the main causes is gastro-esophageal-reflux disease (GERD). The differentiation of a EGT carcinoma in three subtypes is important for therapy: adenocarcinoma of the distal esophagus (type I), cardia carcinoma (type II) and subcardial gastric carcinoma (type III). The most important risk-factor for type I-cancers is "barrett's metaplasia" resulting from GERD over years. The risks for the type II- and type III-carcinomas may be obesity and high caloric and fat intake. The role of Helicobacter pylori infection and adenocarcinoma of the subcardia is unproven. Preoperative tumor staging is difficult and tumor-stage is most often underestimated (esp. in the case of a high-grade dysplasia where in 43% carcinomas one already established). Therapy for all three types of EGJ tumors is surgical. Transhiatal (rarely transthoracic) esophagectomy with lymphadenectomy and proximal gastrectomy is performed for type-I-tumors, type-II and III-tumors are treated like a gastric cancer with total gastrectomy, lymphadenectomy and distal esophagectomy. Lymph-node metastases and advanced tumor-stage are bad prognostic factors, complete tumor resection (R0 resection) with extended lymphadenectomy will improve prognosis. The results of a preoperative combined-modality therapy are encouraging, but have not yet shown a definitive benefit. In case of distant metastases, radio-chemotherapy combined with gastroenterologic treatments (e.g. esophageal prostheses, PEG, etc.) will be used as a palliative treatment option.
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PMID:[Carcinomas of the esophago-gastric junction: surgical strategies]. 1281 32

It has been suggested that elevated leptin levels underlie the low grade proinflammatory state in human obesity. We reasoned that if elevated leptin levels are an important factor in the proinflammatory state in obesity, then exogenous leptin administration during weight loss should counteract the concurrent beneficial effects of weight loss on the proinflammatory state. We therefore determined whether long-acting pegylated recombinant leptin (PEG-OB) prevents the decrease in cellular and humoral inflammation parameters during a very low calorie diet in healthy overweight young men. Except for B cells, PEG-OB treatment did not influence the decline in total leukocyte count and mononuclear subfractions during the diet. Weight loss decreased the humoral inflammation parameters TNFalpha, tissue plasminogen activator, and von Willebrand factor (P < 0.05), but in combination with PEG-OB treatment, a significant decrease was shown for inflammation markers as a whole (P < 0.014) and that of the individual parameters tissue plasminogen activator, von Willebrand factor, plasminogen activator inhibitor type 1, and intercellular adhesion molecule-1 (P < 0.05). The increase in C-reactive protein levels (P < 0.05) was the sole indication for a humoral proinflammatory action of leptin. Although PEG-OB treatment significantly increased weight loss (P < 0.03), the data do not support a proinflammatory role of leptin in human obesity.
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PMID:Leptin and the proinflammatory state associated with human obesity. 1507 Sep 44

Ghrelin, an acylated peptide secreted from the stomach, acts as a short-term signal of nutrient depletion. Ghrelin is an endogenous ligand for the GH secretagogue receptor 1a, a G protein-coupled receptor expressed in the hypothalamus and pituitary. We used a synthetic oligonucleotide, NOX-B11-2, capable of specific high-affinity binding to bioactive ghrelin to determine whether ghrelin neutralization would alter indices of energy balance in vivo. This novel type of ghrelin-blocking agent, called an RNA Spiegelmer (SPM), is a polyethylene glycol-modified l-RNA oligonucleotide, the nonnatural configuration of which confers in vivo stability. NOX-B11-2 blocked ghrelin mediated activation of GH secretagogue receptor 1a in cell culture (IC50 approximately 5 nm). We explored the effects of acute NOX-B11-2 administration on ghrelin-induced feeding in mice. NOX-B11-2 (66 mg/kg, sc) blocked ghrelin-induced feeding and was without effect on feeding evoked by an orally active nonpeptide ghrelin receptor agonist. We demonstrated that selective ghrelin blockade effectively promoted weight loss in diet-induced obese (DIO) mice. Chronic infusion of NOX-B11-2 (33 mg/kg.d, sc) to DIO mice evoked body weight loss for 13 d and reduced food intake and fat mass relative to control SPM-infused mice. In a 7-d study, DIO mice infused with NOX-B11-2 (33 mg/kg.d, sc) showed body weight loss, compared with animals receiving control SPM. This effect was directly mediated by SPM neutralization of ghrelin because NOX-B11-2 administration to ghrelin-deficient mice resulted in no weight loss. The decreased obesity observed in SPM-treated DIO mice provides validation for ghrelin neutralization as a potential antiobesity therapy.
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PMID:Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice. 1633 2

Effective techniques for the cryopreservation of porcine preadipocytes could increase the usefulness of these cells as a model in obesity studies. The objective of this study was to test the effects of the following cryoprotective agents (CPAs) on the cytotoxicity, post-thaw survival, proliferation and differentiation capacity of porcine preadipocytes: ethylene glycol (EG), dimethyl sulphoxide (Me2SO), polyvinylpyrrolidone (PVP), Me2SO+PVP, and no-CPA. In addition to the CPAs, the CPA medium contained 80% DMEM/F12 plus 10% FBS. Trypan blue exclusion tests showed that among the CPA treatments in this study, only EG was toxic to porcine preadipocytes. The highest survival rate (94.96%) and cell viability were obtained when preadipocytes were cryopreserved with 10% PVP. Morphologically, PVP cryopreserved preadipocytes resembled fibroblasts and most underwent attachment, proliferation, and growth arrest with subsequent accumulation of intracellular lipid droplets before becoming mature adipocytes. There were no significant differences in the GPDH activity between adipocytes in the PVP treatment and primary cells from days 3 to 10 of the culture. Analysis of RT-PCR confirmed that there was no significant difference of PPARgamma2 mRNA levels between the cells in the 10% PVP treatment and primary cells. In summary, porcine preadipocytes cryopreserved with DMEM/F12 medium containing 10% PVP and 10% FBS have high survival rate and proliferation potential. Furthermore, the cryopreserved cells synthesize a range of markers that are consistent with this cell type. We conclude that 10% PVP is a suitable CPA for porcine preadipocytes.
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PMID:Effects of different cryoprotectants on the viability and biological characteristics of porcine preadipocyte. 1693 May 80

Stimulation of mu opioid receptors preferentially increases the intake of a high fat diet. In this paper we investigated whether there was a difference in the expression of mu opioid receptors between animals susceptible (Osborne-Mendel) or resistant (S5B/Pl) to obesity induced by eating a high fat diet. Immunohistochemical studies demonstrated that Osborne-Mendel rats eating a chow diet had an increased number of mu opioid receptors in the arcuate nucleus when compared to S5B/Pl rats. These immunohistochemical findings were supported by Real Time-PCR which demonstrated that the mRNA level of mu opioid receptors was also increased in the hypothalamus of Osborne-Mendel rats compared to S5B/Pl rats. Low doses of the mu opioid receptor agonist DAMGO [d-Ala(2)-N-Me-Phe(4)-Glycol(5)]-enkephalin administered to Osborne-Mendel rats caused a significant increase in the preference for a diet high in fat. The same doses of DAMGO switched the diet preference of S5B/Pl rats to high fat but did not significantly increase food intake. The combination of these findings suggests that the increased levels of hypothalamic mu opioid receptors in Osborne-Mendel rats may contribute to their preference for a diet high in fat and increase their susceptibility to becoming obese.
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PMID:Increased expression of mu opioid receptors in animals susceptible to diet-induced obesity. 1699 47

This study is designed to evaluate whether the PEGylated conjugated linoleic acid (PCLA) as the pro-drug can have favorable stability, bioavailability, and anti-adipogenic activity in 3T3-L1 cells for anti-obesity when compared with conjugated linoleic acid (CLA) itself. The CLA was simply coupled to poly(ethylene glycol) (PEG) at the melting state without solvents or catalysts through ester linkages between the carboxylic group of CLA and the hydroxyl group of PEG. To confirm of PCLA as the pro-drug, CLA release from PCLA was investigated by using high-performance liquid chromatographic (HPLC), showing that CLA release from PCLA was almost 90% in a nearly continuous fashion over the next 75h. Apoptosis was promoted by both CLA- and PCLA-treatments with increasing concentrations. However, the level of cell apoptosis induced by PCLA was lower than that induced by CLA owing to the biocompatible and hydrophilic properties of PEG. Moreover, the PCLA decreased glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 cells by acting upon major adipocyte marker proteins such as PPARgamma2, C/EBPalpha, and aP2 modulators. Furthermore, either CLA or PCLA stimulated basal, but not isoproterenol-sensitive, lipolysis in our cell model, suggesting that both CLA and PCLA may stimulate lipolysis via hormone sensitive lipase (HSL)-independent mechanisms. These results suggest that the PCLA may prove to be a stable pro-drug to control the deposition of fat in the human body, and that the anti-adipogenic effect of the PCLA on 3T3-L1 cells will offer a challenging approach for anti-obesity.
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PMID:Down-regulation of PPARgamma2-induced adipogenesis by PEGylated conjugated linoleic acid as the pro-drug: Attenuation of lipid accumulation and reduction of apoptosis. 1708 79

The metabolic syndrome is a main cause for cardiovascular disease and for the accelerating epidemic of chronic renal failure. Previous studies show that 2-hydroxyestradiol (2-HE), an estradiol metabolite with little estrogenic activity, decreases obesity and arterial blood pressure and attenuates the development of renal disease in young, obese, diabetic ZSF1 rats. In humans, however, diabetic renal disease is more frequent and severe in older patients. In vivo, 2-HE is readily converted to 2-methoxyestradiol (2-ME), an estradiol metabolite with no estrogenic activity. Accordingly, one purpose of this study was to determine whether 2-ME would provide benefit in aged rats with a very severe form of diabetic renal disease. Another objective was to determine whether synthetic analogs of estradiol metabolites might be beneficial in diabetic renal disease. To achieve these objectives we examined the effects of 2-ME and its analog 2-ethoxyestradiol (2-EE) in aged (35-week-old), obese ZSF1 rats. Animals were treated for 9 weeks with vehicle (PEG-400, 0.5 microL per hour), 2-ME or 2-EE (18 microg/kg per hour). Metabolic and renal function were measured at weeks 0, 3, 6, and 9, and renal hemodynamics and excretory function were assessed at week 9. Aged ZSF1 rats had elevated levels of glycosylated hemoglobin; increased renal cortical expression of proliferating cell nuclear antigen (PCNA), nuclear factor kappa B (NF-kappaB), and vascular endothelial growth factor (VEGF); glycosuria, hypertension; and proteinuria. 2-ME and 2-EE did not affect obesity or hypertension and had variable effects on glucose homeostasis, yet they attenuated proteinuria; increased renal blood flow and glomerular filtration; and reduced renal cortical expression of PCNA, NFkappaB, and VEGF. We conclude that 2ME and 2EE are strikingly renoprotective even in aged animals with severe diabetic renal disease. The present study warrants further investigation of 2-ME and analogs of estradiol metabolites for treatment of kidney disease associated with the metabolic syndrome.
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PMID:2-Methoxyestradiol and 2-ethoxyestradiol retard the progression of renal disease in aged, obese, diabetic ZSF1 rats. 1726 64


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