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

Adipose cells grown in sub-culture are useful to elucidate genetic factors in obesity. Most omental adipose cell strains from 140 massively obese (greater than 170 percent of reference body weight) subjects replicated, in successive sub-cultures, to a significantly higher degree than cells from lean or moderately obese persons. The difference was due to a greater number of rapidly dividing clones. Adipose cells from the massively obese related into the culture medium proteins, native Mr 20,000-65,000, mitogenic on rat preadipocytes. Mitogenic activity of the medium was much less evident with cells from the lean. In the case of several cell strains, culture with 17-beta-estradiol increased the mitogenic activity of the medium. Omental adipose tissue of the massive obese also contained a greater number of adipose cell clones susceptible to differentiation. Hybrids of adipose cells from the massively obese fused with murine renal adenocarcinoma cells (RAG) revealed more prominent differentiation than hybrids comprised of adipose cells from the lean. Further, only those comprised of adipose cells from the obese could recapitulate differentiation in sub-cultures. These findings in culture probably reflect major heritable factors that facilitate the development of massive obesity in humans.
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PMID:Abnormalities of adipose cells in massive obesity. 208 13

Islets of Langerhans in sections from the tail of the pancreas of corpulent LA/N-cp rats and lean controls aged 1, 3, 6 and 9 mo were examined by immunocytochemistry and morphometrically using an automatic image analyzer. The corpulent rats had significantly greater islet volumes at all ages, although islet hypertrophy tended to plateau after 6 mo. By 12 mo age the architecture of the islets was disrupted with large islets fused and showing areas of fibrosis and deposits of hemosiderin. The volume density (v/v, %) of islets in the parenchyma was significantly increased at each age step in corpulent rats reaching over 20% at 9 mo, and was greater in corpulent than in lean rats at all ages. In the corpulent rats, B-cell volume density dramatically with age and at all ages was significantly greater in corpulent than in lean rats. A-cell volume density was significantly greater in the corpulent rats than in lean rats at 1 and 9 mo. The mean B:A cell ratio was greater in corpulent than in lean rats at 3, 6 and 9 mo. There were more D cells per islet in corpulent than in lean rats up to 9 mo. These changes in cell populations were paralleled by qualitative changes in islet morphology and cellular topography such as increasingly irregular islet shape in corpulent animals and by variations in plasma levels of insulin and glucagon. In this strain of rats, obesity is associated with major changes in pancreatic morphology and this correlates strongly with the susceptibility of the strain to atherosclerosis.
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PMID:Age-related qualitative and quantitative changes in the endocrine pancreas of the LA/N-corpulent rat. 332 19

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

Adrenalectomized female rats with lesions of the ventromedial hypothalamus or sham lesions were given SC implants of wax pellets or a fused mixture of corticosterone-cholesterol (40, 75, or 130% by weight). In animals with sham lesions, high dosages of corticosterone proved to be catabolic (r = -0.61 between plasma corticosterone and weight change). In marked contrast, animals with VMH lesions displayed substantial weight gains at all circulating levels of corticosterone, with a significant positive correlation (r = +0.48) between these two variables. It is concluded that: a) damage to the basomedial hypothalamus alters an organism's response to corticosterone at both ends of the dose-response curve, and b) both Type I and Type II corticosterone receptors in the brain play a role in hypothalamic obesity.
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PMID:Level of corticosterone replacement determines body weight gain in adrenalectomized rats with VMH lesions. 829 62

From October 1988 through November 1990, 29 lumbar and lumbosacral spine fusion patients, 11 instrumented and 18 noninstrumented, were observed. Seventeen were men and 12 were women, with a mean age of 42.6 years (range, 22-83). The narcotic equivalent (NE) in milligrams/kilogram/day of medication used was analyzed. Age, sex, height, and weight were compared to the type, dose, mode, and duration of medication administration. Morphine was the reference point narcotic at 1.0:1.0. Levels fused, use of instrumentation, and prior surgery were related to NE. No significant differences in age, total body weight, height, levels fused, or hospital stay were established. There were 89.6% of patients over the ideal body weight by a mean 17.47 kg or 38.3 lb. The mean population NE was 3.76 mg/kg/day. Prior surgery patients tended to request narcotics intramuscularly for a longer period, while older patients tended to receive less medication. Patient obesity was related to lower NE. This study could not demonstrate a decrease in postoperative pain as it relates to the amount of narcotic medication received with the use of pedicle instrumentation.
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PMID:Influence of pedicle fixation on postoperative pain. 850 26

The melanocortin receptor type 4 (MC4-R) is involved in food intake and represents a potential target for the treatment of some forms of obesity. The fluorescent protein EGFP was fused to the wild-type or mutated coding sequence of the human MC4-R. After transfection in HEK 293, clones stably expressing hMC4-R-EGFP were selected. Wild-type chimeric hMC4-R was well addressed to the cell membrane as demonstrated using confocal microscopy and displayed the same pharmacological characteristics as native hMC4R. NDP-alpha MSH induced a time-dependent internalization of MC4-R that was partially prevented by AgRP. The two mutated chimeric receptors studied here (CTCT-deleted and C271A) showed a high alteration of their response to ligand and were retained inside the cells. In conclusion, we have developed a model of clones stably expressing EGFP-tagged-hMC4-R. This is the only such model available to date and it provides a useful tool to follow the trafficking of MC4-R inside living cells.
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PMID:Characterization of cell lines stably expressing human normal or mutated EGFP-tagged MC4R. 1511 80

Plant flavonoids are widely distributed polyphenolic compounds of the human diet. They consist of six major classes based on specific structural differences: flavonols, flavones, flavanones, catechins, anthocyanidins, and isoflavones. All of the major classes of flavonoids are comprised of three six-membered rings: an aromatic A-ring fused to a heterocyclic C-ring that is attached through a single carbon-carbon bond to an aromatic Bring. Population studies have shown that flavonoid intake is inversely correlated with mortality from cardiovascular disease, and numerous flavonoids of dietary significance have been shown to beneficially impact parameters associated with atherosclerosis, including lipoprotein oxidation, blood platelet aggregation, and vascular reactivity. Therapeutic effects of flavonoids on platelet aggregability and blood pressure have been attributed to competitive inhibition of cyclic nucleotide phosphodiesterase (PDE), an elevation in cAMP level, and subsequent activation of protein kinase A (cAMP-dependent protein kinase). In addition, flavonoids may induce neutral lipid hydrolysis from lipid stores through PDE inhibition in adipose tissue and liver. Indeed, the three-dimensional structure of many flavonoids is sterically and electrostatically compatible with the catalytic site of cAMP PDE3 and PDE4. Flavonoids have also been reported to suppress pathways of lipid biosynthesis and of very low-density lipoprotein production in cultured hepatocytes. Continued studies of the biochemical mechanisms underlying the biological effects of plant flavonoids may uncover new strategies for the treatment of cardiovascular disease, as well as associated conditions such as obesity, hepatic steatosis, and Type 2 diabetes.
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PMID:Flavonoids attenuate cardiovascular disease, inhibit phosphodiesterase, and modulate lipid homeostasis in adipose tissue and liver. 1694 97

The primate-specific gene family, POTE, is expressed in many cancers but only in a limited number of normal tissues (testis, ovary, prostate). The 13 POTE paralogs are dispersed among 8 human chromosomes. They evolved by gene duplication and remodeling from an ancestral gene, Ankrd26, recently implicated in controlling body size and obesity. In addition, several POTE paralogs are fused to an actin retrogene producing POTE-actin fusion proteins. The biological function of the POTE genes is unknown, but their high expression in primary spermatocytes, some of which are undergoing apoptosis, suggests a role in inducing programmed cell death. We have chosen Hela cells as a model to study POTE function in human cancer, and have identified POTE-2alpha-actin as the major transcript and the protein it encodes in Hela cells. Transfection experiments show that both POTE-2alpha-actin and POTE-2gammaC are localized to actin filaments close to the inner plasma membrane. Transient expression of POTE-2alpha-actin or POTE-2gammaC induces apoptosis in Hela cells. Using wild-type and mutant mouse embryo cells, we find apoptosis induced by over-expression of POTE-2gammaC is decreased in Bak ( -/- ) or Bak ( -/- ) Bax ( -/- ) cells indicating POTE is acting through a mitochondrial pathway. Endogenous POTE-actin protein levels but not RNA levels increased in a time dependent manner by stimulation of death receptors with their cognate ligands. Our data indicates that the POTE gene family encodes a new family of proapoptotic proteins.
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PMID:A primate-specific POTE-actin fusion protein plays a role in apoptosis. 1966 88

The growth hormone secretagogue receptor type 1a (GHS-R1a) belongs to class A G-protein-coupled receptors (GPCR). This receptor mediates pleiotropic effects of ghrelin and represents a promising target for dysfunctions of growth hormone secretion and energy homeostasis including obesity. Identification of new compounds which bind GHS-R1a is traditionally achieved using radioactive binding assays. Here we propose a new fluorescence-based assay, called Tag-lite binding assay, based on a fluorescence resonance energy transfer (FRET) process between a terbium cryptate covalently attached to a SNAP-tag fused GHS-R1a (SNAP-GHS-R1a) and a high-affinity red fluorescent ghrelin ligand. The long fluorescence lifetime of the terbium cryptate allows a time-resolved detection of the FRET signal. The assay was made compatible with high-throughput screening by using prelabeled cells in suspension under a 384-well plate format. K(i) values for a panel of 14 compounds displaying agonist, antagonist, or inverse agonist properties were determined using both the radioactive and the Tag-lite binding assays performed on the same batches of GHS-R1a-expressing cells. Compound potencies obtained in the two assays were nicely correlated. This study is the first description of a sensitive and reliable nonradioactive binding assay for GHS-R1a in a format amenable to high-throughput screening.
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PMID:Homogeneous time-resolved fluorescence-based assay to screen for ligands targeting the growth hormone secretagogue receptor type 1a. 2093 74

The incretin hormone glucagon-like peptide-1 (GLP-1) exerts important functions in controlling glucose and energy homeostasis. Endogenous GLP-1 has a very short half-life due to DPP-IV-mediated degradation and renal clearance, which limits the therapeutic use of native GLP-1. We have shown previously that immunoglobulin fragment-fused GLP-1 (GLP-1/Fc) is a structurally stable GLP-1 analog. Here, we report a non-viral GLP-1/Fc gene therapy strategy utilizing a REP78-in-trans and REB-in-cis element system to achieve a site-specific genomic integration. For this purpose, the GLP-1/Fc expression cassette, which is fused with the RBE element, was co-injected with the Rep78 plasmid into the muscles of transgenic mice carrying the AAVS1 locus of human chromosome 19. The Rep protein-mediated site-specific integration was demonstrated by nested PCR, dot-blot, and Southern blotting. We found that this approach reduced weight gain and improved lipid profiles in the AAVS1-mice on high-fat diet challenge. Our observations reveal a new GLP-1 therapeutic strategy with an apparent absence of side effects, which may find applications in diabetes treatment and obesity prevention.
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PMID:A site-specific genomic integration strategy for sustained expression of glucagon-like peptide-1 in mouse muscle for controlling energy homeostasis. 2107 Jul 45


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