Peptidoglycan cross-linking in glycopeptide-resistant Actinomycetales.

PubMed

Hugonnet, Jean-Emmanuel; Haddache, Nabila; Veckerlé, Carole; Dubost, Lionel; Marie, Arul; Shikura, Noriyasu; Mainardi, Jean-Luc; Rice, Louis B; Arthur, Michel

2014-01-01

Synthesis of peptidoglycan precursors ending in D-lactate (D-Lac) is thought to be responsible for glycopeptide resistance in members of the order Actinomycetales that produce these drugs and in related soil bacteria. More recently, the peptidoglycan of several members of the order Actinomycetales was shown to be cross-linked by L,D-transpeptidases that use tetrapeptide acyl donors devoid of the target of glycopeptides. To evaluate the contribution of these resistance mechanisms, we have determined the peptidoglycan structure of Streptomyces coelicolor A(3)2, which harbors a vanHAX gene cluster for the production of precursors ending in D-Lac, and Nonomuraea sp. strain ATCC 39727, which is devoid of vanHAX and produces the glycopeptide A40296. Vancomycin retained residual activity against S. coelicolor A(3)2 despite efficient incorporation of D-Lac into cytoplasmic precursors. This was due to a D,D-transpeptidase-catalyzed reaction that generated a stem pentapeptide recognized by glycopeptides by the exchange of D-Lac for D-Ala and Gly. The contribution of L,D-transpeptidases to resistance was limited by the supply of tetrapeptide acyl donors, which are essential for the formation of peptidoglycan cross-links by these enzymes. In the absence of a cytoplasmic metallo-D,D-carboxypeptidase, the tetrapeptide substrate was generated by hydrolysis of the C-terminal D-Lac residue of the stem pentadepsipeptide in the periplasm in competition with the exchange reaction catalyzed by D,D-transpeptidases. In Nonomuraea sp. strain ATCC 39727, the contribution of L,D-transpeptidases to glycopeptide resistance was limited by the incomplete conversion of pentapeptides into tetrapeptides despite the production of a cytoplasmic metallo-D,D-carboxypeptidase. Since the level of drug production exceeds the level of resistance, we propose that L,D-transpeptidases merely act as a tolerance mechanism in this bacterium.

N-Glycan Structure Annotation of Glycopeptides Using a Linearized Glycan Structure Database (GlyDB)

PubMed Central

Ren, Jian Min; Rejtar, Tomas; Li, Lingyun; Karger, Barry L.

2008-01-01

While glycoproteins are abundant in nature, and changes in glycosylation occur in cancer and other diseases, glycoprotein characterization remains a challenge due to the structural complexity of the biopolymers. This paper presents a general strategy, termed GlyDB, for glycan structure annotation of N-linked glycopeptides from tandem mass spectra in the LC-MS analysis of proteolytic digests of glycoproteins. The GlyDB approach takes advantage of low-energy collision induced dissociation of N-linked glycopeptides that preferentially cleaves the glycosidic bonds while the peptide backbone remains intact. A theoretical glycan structure database derived from biosynthetic rules for N-linked glycans was constructed employing a novel representation of branched glycan structures consisting of multiple linear sequences. The commonly used peptide identification program, Sequest, could then be utilized to assign experimental tandem mass spectra to individual glycoforms. Analysis of synthetic glycopeptides and well-characterized glycoproteins demonstrate that the GlyDB approach can be a useful tool for annotation of glycan structures and for selection of a limited number of potential glycan structure candidates for targeted validation. PMID:17625816

The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis

PubMed Central

Ding, Xiu-Li; Man, Ya-Nan; Hao, Jian; Zhu, Cui-Hong; Liu, Chang; Yang, Xue

2016-01-01

Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs). Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining. Results. In vitro, GSPP (10 μg/mL, 100 μg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P < 0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis. Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis. PMID:27190997

Automated glycopeptide analysis—review of current state and future directions

PubMed Central

Dallas, David C.; Martin, William F.; Hua, Serenus

2013-01-01

Glycosylation of proteins is involved in immune defense, cell–cell adhesion, cellular recognition and pathogen binding and is one of the most common and complex post-translational modifications. Science is still struggling to assign detailed mechanisms and functions to this form of conjugation. Even the structural analysis of glycoproteins—glycoproteomics—remains in its infancy due to the scarcity of high-throughput analytical platforms capable of determining glycopeptide composition and structure, especially platforms for complex biological mixtures. Glycopeptide composition and structure can be determined with high mass-accuracy mass spectrometry, particularly when combined with chromatographic separation, but the sheer volume of generated data necessitates computational software for interpretation. This review discusses the current state of glycopeptide assignment software—advances made to date and issues that remain to be addressed. The various software and algorithms developed so far provide important insights into glycoproteomics. However, there is currently no freely available software that can analyze spectral data in batch and unambiguously determine glycopeptide compositions for N- and O-linked glycopeptides from relevant biological sources such as human milk and serum. Few programs are capable of aiding in structural determination of the glycan component. To significantly advance the field of glycoproteomics, analytical software and algorithms are required that: (i) solve for both N- and O-linked glycopeptide compositions, structures and glycosites in biological mixtures; (ii) are high-throughput and process data in batches; (iii) can interpret mass spectral data from a variety of sources and (iv) are open source and freely available. PMID:22843980

Hexose rearrangements upon fragmentation of N-glycopeptides and reductively aminated N-glycans.

PubMed

Wuhrer, Manfred; Koeleman, Carolien A M; Deelder, André M

2009-06-01

Tandem mass spectrometry of glycans and glycoconjugates in protonated form is known to result in rearrangement reactions leading to internal residue loss. Here we studied the occurrence of hexose rearrangements in tandem mass spectrometry of N-glycopeptides and reductively aminated N-glycans by MALDI-TOF/TOF-MS/MS and ESI-ion trap-MS/MS. Fragmentation of proton adducts of oligomannosidic N-glycans of ribonuclease B that were labeled with 2-aminobenzamide and 2-aminobenzoic acid resulted in transfer of one to five hexose residues to the fluorescently tagged innermost N-acetylglucosamine. Glycopeptides from various biological sources with oligomannosidic glycans were likewise shown to undergo hexose rearrangement reactions, resulting in chitobiose cleavage products that have acquired one or two hexose moieties. Tryptic immunoglobulin G Fc-glycopeptides with biantennary N-glycans likewise showed hexose rearrangements resulting in hexose transfer to the peptide moiety retaining the innermost N-acetylglucosamine. Thus, as a general phenomenon, tandem mass spectrometry of reductively aminated glycans as well as glycopeptides may result in hexose rearrangements. This characteristic of glycopeptide MS/MS has to be considered when developing tools for de novo glycopeptide structural analysis.

Separation and Identification of Isomeric Glycopeptides by High Field Asymmetric Waveform Ion Mobility Spectrometry

PubMed Central

2012-01-01

The analysis of intact glycopeptides by mass spectrometry is challenging due to the numerous possibilities for isomerization, both within the attached glycan and the location of the modification on the peptide backbone. Here, we demonstrate that high field asymmetric wave ion mobility spectrometry (FAIMS), also known as differential ion mobility, is able to separate isomeric O-linked glycopeptides that have identical sequences but differing sites of glycosylation. Two glycopeptides from the glycoprotein mucin 5AC, GT(GalNAc)TPSPVPTTSTTSAP and GTTPSPVPTTST(GalNAc)TSAP (where GalNAc is O-linked N-acetylgalactosamine), were shown to coelute following reversed-phase liquid chromatography. However, FAIMS analysis of the glycopeptides revealed that the compensation voltage ranges in which the peptides were transmitted differed. Thus, it is possible at certain compensation voltages to completely separate the glycopeptides. Separation of the glycopeptides was confirmed by unique reporter ions produced by supplemental activation electron transfer dissociation mass spectrometry. These fragments also enable localization of the site of glycosylation. The results suggest that glycan position plays a key role in determining gas-phase glycopeptide structure and have implications for the application of FAIMS in glycoproteomics. PMID:22280549

Study on oxidative metabolism of S180 cells induced by meretrix glycopeptide

NASA Astrophysics Data System (ADS)

Wu, Jielian; Wang, Ping; Kang, Huizhu

2017-03-01

Previous in vitro researches have showed that MGP0501, a natural glycopeptide isolated from Meretrix meretrix, can inhibit proliferation or induce apoptosis in human gastric carcinoma, lung cance (A549), Leukemia K562, mouse melanoma B16, hepatoma or breast cancer cells (MDA-MB-231). In this study, we performed an in vivo study to investigate the anti-tumor effect and mechanisms of MGP0501 on xenografted sarcoma 180 (S180) in mice. Results revealed that the inhibition rates of S180 on solid tumors were 69.72%, with a concentration of 6 mg/kg MGP0501,which was significantly higher than that of CTX. In addition, the biochemical metabolism analysis showed that MGP0501 could enhance the activities of glutathione tablets (GSH-Px) and catalase (CAT) and supersxide dismutase (SOD) in liver of mice. The content of malondialdehyde (MDA) in liver, on the contrary, was decreased. The promotion to antioxidation and the elimination of free radical in liver also attribute the antitumor activity of MGP0501. These results indicated that in vivo antitumor activity is associated with enhanced antioxidant capacity in S180 xenografts-bearing mice.

Antifreeze glycopeptide diastereomers.

PubMed

Nagel, Lilly; Budke, Carsten; Dreyer, Axel; Koop, Thomas; Sewald, Norbert

2012-01-01

Antifreeze glycopeptides (AFGPs) are a special class of biological antifreeze agents, which possess the property to inhibit ice growth in the body fluids of arctic and antarctic fish and, thus, enable life under these harsh conditions. AFGPs are composed of 4-55 tripeptide units -Ala-Ala-Thr- glycosylated at the threonine side chains. Despite the structural homology among all the fish species, divergence regarding the composition of the amino acids occurs in peptides from natural sources. Although AFGPs were discovered in the early 1960s, the adsorption mechanism of these macromolecules to the surface of the ice crystals has not yet been fully elucidated. Two AFGP diastereomers containing different amino acid configurations were synthesized to study the influence of amino acid stereochemistry on conformation and antifreeze activity. For this purpose, peptides containing monosaccharide-substituted allo-L- and D-threonine building blocks were assembled by solid-phase peptide synthesis (SPPS). The retro-inverso AFGP analogue contained all amino acids in D-configuration, while the allo-L-diastereomer was composed of L-amino acids, like native AFGPs, with replacement of L-threonine by its allo-L-diastereomer. Both glycopeptides were analyzed regarding their conformational properties, by circular dichroism (CD), and their ability to inhibit ice recrystallization in microphysical experiments.

Antifreeze glycopeptide diastereomers

PubMed Central

Nagel, Lilly; Budke, Carsten; Dreyer, Axel; Koop, Thomas

2012-01-01

Summary Antifreeze glycopeptides (AFGPs) are a special class of biological antifreeze agents, which possess the property to inhibit ice growth in the body fluids of arctic and antarctic fish and, thus, enable life under these harsh conditions. AFGPs are composed of 4–55 tripeptide units -Ala-Ala-Thr- glycosylated at the threonine side chains. Despite the structural homology among all the fish species, divergence regarding the composition of the amino acids occurs in peptides from natural sources. Although AFGPs were discovered in the early 1960s, the adsorption mechanism of these macromolecules to the surface of the ice crystals has not yet been fully elucidated. Two AFGP diastereomers containing different amino acid configurations were synthesized to study the influence of amino acid stereochemistry on conformation and antifreeze activity. For this purpose, peptides containing monosaccharide-substituted allo-L- and D-threonine building blocks were assembled by solid-phase peptide synthesis (SPPS). The retro-inverso AFGP analogue contained all amino acids in D-configuration, while the allo-L-diastereomer was composed of L-amino acids, like native AFGPs, with replacement of L-threonine by its allo-L-diastereomer. Both glycopeptides were analyzed regarding their conformational properties, by circular dichroism (CD), and their ability to inhibit ice recrystallization in microphysical experiments. PMID:23209499

Affinity entrapment of oligosaccharides and glycopeptides using free lectin solution.

PubMed

Yodoshi, Masahiro; Oyama, Takehiro; Masaki, Ken; Kakehi, Kazuaki; Hayakawa, Takao; Suzuki, Shigeo

2011-01-01

Two procedures were proposed for the specific recovery of fluorescent derivatives of glycoprotein-derived oligosaccharides and tryptic glycopeptides using certain plant lectins. The first was based on the salting out of oligosaccharide-lectin conjugates with ammonium sulfate. Oligosaccharides specifically bound to lectins were recovered free from lectins using ethanol precipitation after dissolution in water. This method enabled group separation of 2-aminopyridine-labeled oligosaccharides derived from ovalbumin to galacto-oligosaccharides and agalacto-oligosaccharides by Ricinus communis agglutinin, and to high mannose- and hybrid-type oligosaccharides by wheat-germ agglutinin. Fractional precipitation based on differences in affinity for concanavalin A was accomplished by adding an appropriate concentration of methyl α-mannoside as an inhibitor. In the second method, tryptic digests of glycoproteins were mixed with a lectin solution, and the glycopeptide-lectin conjugates were specifically trapped on a centrifugal ultrafiltration membrane with cut-off of 10 kD. Trapped glycopeptides, as retentates, were passed through membranes by resuspension in diluted acid. This method is particularly useful for the enrichment of glycopeptides in protease digestion mixtures for glycosylation analyses by liquid chromatography-mass spectrometry.

Characterization of Glycan Structures of Chondroitin Sulfate-Glycopeptides Facilitated by Sodium Ion-Pairing and Positive Mode LC-MS/MS

NASA Astrophysics Data System (ADS)

Nilsson, Jonas; Noborn, Fredrik; Gomez Toledo, Alejandro; Nasir, Waqas; Sihlbom, Carina; Larson, Göran

2017-02-01

Purification and liquid chromatography-tandem mass spectrometry (LC-MS/MS) characterization of glycopeptides, originating from protease digests of glycoproteins, enables site-specific analysis of protein N- and O-glycosylations. We have described a protocol to enrich, hydrolyze by chondroitinase ABC, and characterize chondroitin sulfate-containing glycopeptides (CS-glycopeptides) using positive mode LC-MS/MS. The CS-glycopeptides, originating from the Bikunin proteoglycan of human urine samples, had ΔHexAGalNAcGlcAGalGalXyl- O-Ser hexasaccharide structure and were further substituted with 0-3 sulfate and 0-1 phosphate groups. However, it was not possible to exactly pinpoint sulfate attachment residues, for protonated precursors, due to extensive fragmentation of sulfate groups using high-energy collision induced dissociation (HCD). To circumvent the well-recognized sulfate instability, we now introduced Na+ ions to form sodiated precursors, which protected sulfate groups from decomposition and facilitated the assignment of sulfate modifications. Sulfate groups were pinpointed to both Gal residues and to the GalNAc of the hexasaccharide structure. The intensities of protonated and sodiated saccharide oxonium ions were very prominent in the HCD-MS2 spectra, which provided complementary structural analysis of sulfate substituents of CS-glycopeptides. We have demonstrated a considerable heterogeneity of the bikunin CS linkage region. The realization of these structural variants should be beneficial in studies aimed at investigating the importance of the CS linkage region with regards to the biosynthesis of CS and potential interactions to CS binding proteins. Also, the combined use of protonated and sodiated precursors for positive mode HCD fragmentation analysis will likely become useful for additional classes of sulfated glycopeptides.

Synthesis, Properties, and Mechanism of Action of New Generation of Polycyclic Glycopeptide Antibiotics.

PubMed

Olsufyeva, Eugenia N; Tevyashova, Anna N

2017-01-01

The increased resistance of glycopeptide based antibiotics has become a serious problem for the chemotherapy of infections triggered by resistant Gram-positive bacteria. This has motivated the urgent sincere efforts to develop potent glycopeptide-based antibiotics in both academy and industry research laboratories. Understanding of the mechanism of action of natural and modified glycopeptides is considered as the basis for the rational design of compounds with valuable properties to achieve the fundamental results. Several hydrophobic glycopeptide analogues active against resistant strains were developed during the last two decades. Three drugs, namely, oritavancin, telavancin and dalbavancin were approved by FDA in 2013-2014. It was found that hydrophobic derivatives act through different mechanisms without binding with the modified target of resistant bacteria. Types: Different types of chemical modifications led to several glycopeptide analogues active against Gram-negative bacteria as advocated by in vitro studies or demonstrating potent antiviral activity in the cell models. A new class of glycopeptide antibiotics with potent activity against sensitive and resistant bacterial strains has been recently reported with the aim to overcome the resistance, however, there are a lot of obscure problems in the complete understanding of their mechanisms of actions. In this review, we summarized the achievements of synthetic methods devoted to the construction of new polycyclic glycopeptide antibiotics and described the studies related to their mechanism of actions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synthesis and study of antibacterial activities of antibacterial glycopeptide antibiotics conjugated with benzoxaboroles.

PubMed

Printsevskaya, S S; Reznikova, M I; Korolev, A M; Lapa, G B; Olsufyeva, E N; Preobrazhenskaya, M N; Plattner, J J; Zhang, Y K

2013-04-01

The ability of boron-containing compounds to undergo a number of novel binding interactions with drug target functional groups has recently been described. In an extension of this work, we have incorporated a boron-containing scaffold, the benzoxaborole, into several glycopeptides antibiotics. The aim of this work is to exploit the inherent reactivity of boron to gain additional interactions with the bacterial cell wall components to improve binding affinity and to thereby overcome resistance. Three antibacterial glycopeptides (vancomycin, eremomycin and teicoplanin aglycone) have been selected for the construction of a series of 12 new benzoxaborole-glycopeptide conjugates. The hybrid antibiotics, in which the benzoxaborole and glycopeptide moieties were separated by a linker, exhibited excellent antibacterial activity against Gram-positive bacteria, including those with intermediate susceptibility to glycopeptides. Some analogs also demonstrated activity against vancomycin-resistant enterococci. Conjugation of antibiotics with benzoxaborole derivatives provides antibiotics with new and useful properties. Teicoplanin aglycone-benzoxaborole derivatives overcome resistance of Gram-positive bacteria to vancomycin.

It is all about the solvent: on the importance of the mobile phase for ZIC-HILIC glycopeptide enrichment.

PubMed

Alagesan, Kathirvel; Khilji, Sana Khan; Kolarich, Daniel

2017-01-01

Glycopeptide enrichment is a crucial step in glycoproteomics for which hydrophilic interaction chromatography (HILIC) has extensively been applied due to its low bias towards different glycan types. A systematic evaluation of applicable HILIC mobile phases on glycopeptide enrichment efficiency and selectivity is, to date, however, still lacking. Here, we present a novel, simplified technique for HILIC enrichment termed "Drop-HILIC", which was applied to systematically evaluate the mobile phase effect on ZIC-HILIC (zwitterionic type of hydrophilic interaction chromatography) glycopeptide enrichment. The four most commonly used MS compatible organic solvents were investigated: (i) acetonitrile, (ii) methanol, (iii) ethanol and (iv) isopropanol. Glycopeptide enrichment efficiencies were evaluated for each solvent system using samples of increasing complexity ranging from well-defined synthetic glycopeptides spiked into different concentrations of tryptic BSA peptides, followed by standard glycoproteins, and a complex sample derived from human (depleted and non-depleted) serum. ZIC-HILIC glycopeptide efficiency largely relied upon the used solvent. Different organic mobile phases enriched distinct glycopeptide subsets in a peptide backbone hydrophilicity-dependant manner. Acetonitrile provided the best compromise for the retention of both hydrophilic and hydrophobic glycopeptides, whereas methanol was confirmed to be unsuitable for this purpose. The enrichment efficiency of ethanol and isopropanol towards highly hydrophobic glycopeptides was compromised as considerable co-enrichment of unmodified peptides occurred, though for some hydrophobic glycopeptides isopropanol showed the best enrichment properties. This study shows that even minor differences in the peptide backbone and solvent do significantly influence HILIC glycopeptide enrichment and need to be carefully considered when employed for glycopeptide enrichment. Graphical Abstract The organic solvent plays a

A42867, a novel glycopeptide antibiotic.

PubMed

Riva, E; Gastaldo, L; Beretta, M G; Ferrari, P; Zerilli, L F; Cassani, G; Selva, E; Goldstein, B P; Berti, M; Parenti, F

1989-04-01

A42867 is a new glycopeptide antibiotic of the ristocetin-vancomycin class active against aerobic and anaerobic Gram-positive bacteria. A42867 is produced by a strain of Nocardia nov. sp. ATCC 53492. A42867 was isolated during a screening program aimed at the discovery of new members of this glycopeptide class of antibiotics, by affinity chromatography based on an acyl-D-alanyl-D-alanine probe. The structure of A42867 was elucidated by fast atom bombardment MS, high field 2D 1H NMR spectroscopy, and HPLC analysis of the hydrolyzed carbohydrates. A42867 differs from vancomycin in the sugar portion and in the presence of only one chlorine atom in the peptide core. Its biological activity on Gram-positive aerobic and anaerobic bacteria is similar to that of other antibiotics of this group.

Native N-glycopeptide thioester synthesis through N→S acyl transfer

PubMed Central

Premdjee, Bhavesh; Adams, Anna L.; Macmillan, Derek

2011-01-01

Peptide thioesters are important tools for the total synthesis of proteins using native chemical ligation (NCL). Preparation of glycopeptide thioesters, that enable the assembly of homogeneously glycosylated proteins, is complicated by the perceived fragile nature of the sugar moiety. Herein, we demonstrate the compatibility of thioester formation via N→S acyl transfer with native N-glycopeptides and report observations that will aid in their preparation. PMID:21676613

Glycopeptide use is associated with increased mortality in Enterococcus faecalis bacteraemia.

PubMed

Foo, Hong; Chater, Mathew; Maley, Michael; van Hal, Sebastiaan J

2014-08-01

Enterococci are an important cause of nosocomial and community-acquired infections, with bacteraemia being one of the most common presentations. Although inappropriate antimicrobial therapy has been associated with poorer outcomes in Enterococcus faecalis (EF) bacteraemia, the impact of antimicrobial choice, namely β-lactam versus glycopeptide therapy, has not been well described. We sought to determine whether choice of antibiotic affects patient outcomes in EF bacteraemia. This retrospective cohort study was conducted at Liverpool and Bankstown Lidcombe Hospitals, Sydney, Australia between 2006 and 2013. Medical records and laboratory data for consecutive EF bacteraemias were reviewed. Clinical and microbiological data were obtained for all patients who received appropriate antimicrobial therapy with either a β-lactam or a glycopeptide antibiotic. Outcomes and predictors of mortality were determined and treatment groups were compared. One hundred and seventy-two episodes of clinically significant EF bacteraemias received appropriate antimicrobial therapy with a β-lactam (n = 126) or a glycopeptide (n = 46). All-cause 30 day mortality was 15.1%, with mortality significantly higher in patients receiving glycopeptide therapy compared with β-lactam therapy (26.1% versus 11.1%, P = 0.015). Glycopeptide therapy remained an independent predictor of 30 day mortality [OR 2.46 (95% CI 1.01-6.02), P = 0.048]. APACHE II score [OR 1.10 (95% CI 1.02-1.18), P = 0.011] and malignancy [OR 2.58 (95% CI 1.03-6.49), P = 0.044] were also independent predictors of 30 day mortality. Glycopeptide use is associated with increased mortality in patients with EF bacteraemia. In the treatment of β-lactam-susceptible EF bacteraemia, β-lactams should be considered first-line therapy. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

PubMed Central

Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

2012-01-01

Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

Chiral Recognition with Macrocyclic Glycopeptides: Mechanisms and Applications

NASA Astrophysics Data System (ADS)

Berthod, Alain; Qiu, Hai Xiao; Staroverov, Sergey M.; Kuznestov, Mikhail A.; Armstrong, Daniel W.

The macrocyclic glycopeptide chiral selectors are natural molecules produced by bacterial fermentation. Purified and bonded to silica particles, they make very useful chiral stationary phases (CSP) with a broad spectrum of applicability in enantiomeric separation. The macrocyclic glycopeptide CSPs are multimodal, the same column being able to work in normal phase mode with apolar mobile phase, in reversed-phase mode, or in polar ionic mode with 100% alcoholic mobile phase of adjusted pH. The role of the carbohydrate units is described as well as the critical charge-charge docking interaction responsible for the amino acid enantiomer recognition. The complimentary phenomenon is also exposed.

Photoinduced Thiol-ene Chemistry Applied to the Synthesis of Self-Assembling Elastin-Inspired Glycopeptides.

PubMed

Piccirillo, Germano; Pepe, Antonietta; Bedini, Emiliano; Bochicchio, Brigida

2017-02-21

Synthetic (glyco)peptides inspired by proteins able to self-assemble are appealing biomaterials in the field of tissue engineering and regenerative medicine. Herein, for the first time, taking advantage of thiol-ene chemistry coupled to solid-phase peptide synthesis, a self-assembling peptide inspired by elastin protein was bioconjugated to three carbohydrates in order to obtain the corresponding glycopeptides. They were studied at the molecular and supramolecular level. The results show that the carbohydrate influences the molecular conformation of the glycopeptide and its self-aggregation properties as well. As future perspective, the results could enable us to tune the final self-aggregation properties of the glycopeptide by changing the sugar moiety. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Harnessing the synthetic capabilities of glycopeptide antibiotic tailoring enzymes: characterization of the UK-68,597 biosynthetic cluster.

PubMed

Yim, Grace; Kalan, Lindsay; Koteva, Kalinka; Thaker, Maulik N; Waglechner, Nicholas; Tang, Irene; Wright, Gerard D

2014-11-24

In this study, a draft genome sequence of Actinoplanes sp. ATCC 53533 was assembled, and an 81-kb biosynthetic cluster for the unusual sulfated glycopeptide UK-68,597 was identified. Glycopeptide antibiotics are important in the treatment of infections caused by Gram-positive bacteria. Glycopeptides contain heptapeptide backbones that are modified by many tailoring enzymes, including glycosyltransferases, sulfotransferases, methyltransferases, and halogenases, generating extensive chemical and functional diversity. Several tailoring enzymes in the cluster were examined in vitro for their ability to modify glycopeptides, resulting in the synthesis of novel molecules. Tailoring enzymes were also expressed in the producer of the glycopeptide aglycone A47934, generating additional chemical diversity. This work characterizes the biosynthetic program of UK-68,597 and demonstrates the capacity to expand glycopeptide chemical diversity by harnessing the unique chemistry of tailoring enzymes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antibody recognition of a unique tumor-specific glycopeptide antigen

PubMed Central

Brooks, Cory L.; Schietinger, Andrea; Borisova, Svetlana N.; Kufer, Peter; Okon, Mark; Hirama, Tomoko; MacKenzie, C. Roger; Wang, Lai-Xi; Schreiber, Hans; Evans, Stephen V.

2010-01-01

Aberrant glycosylation and the overexpression of certain carbohydrate moieties is a consistent feature of cancers, and tumor-associated oligosaccharides are actively investigated as targets for immunotherapy. One of the most common aberrations in glycosylation patterns is the presentation of a single O-linked N-acetylgalactosamine on a threonine or serine residue known as the “Tn antigen.” Whereas the ubiquitous nature of Tn antigens on cancers has made them a natural focus of vaccine research, such carbohydrate moieties are not always tumor-specific and have been observed on embryonic and nonmalignant adult tissue. Here we report the structural basis of binding of a complex of a monoclonal antibody (237mAb) with a truly tumor-specific glycopeptide containing the Tn antigen. In contrast to glycopeptide-specific antibodies in complex with simple peptides, 237mAb does not recognize a conformational epitope induced in the peptide by sugar substitution. Instead, 237mAb uses a pocket coded by germ-line genes to completely envelope the carbohydrate moiety itself while interacting with the peptide moiety in a shallow groove. Thus, 237mAb achieves its striking tumor specificity, with no observed physiological cross-reactivity to the unglycosylated peptide or the free glycan, by a combination of multiple weak but specific interactions to both the peptide and to the glycan portions of the antigen. PMID:20479270

Direct fluorescence polarization assay for the detection of glycopeptide antibiotics.

PubMed

Yu, Linliang; Zhong, Meng; Wei, Yinan

2010-08-15

Glycopeptide antibiotics are widely used in the treatment of infections caused by Gram-positive bacteria. They inhibit the biosynthesis of the bacterial cell wall through binding to the D-alanyl-D-alanine (D-Ala-D-Ala) terminal peptide of the peptidoglycan precursor. Taking advantage of this highly specific interaction, we developed a direct fluorescence polarization based method for the detection of glycopeptide antibiotics. Briefly, we labeled the acetylated tripeptide Ac-L-Lys-D-Ala-D-Ala-OH with a fluorophore to create a peptide probe. Using three glycopeptide antibiotics, vancomycin, teicoplanin, and telavancin, as model compounds, we demonstrated that the fluorescence polarization of the peptide probe increased upon binding to antibiotics in a concentration dependent manner. The dissociation constants (K(d)) between the peptide probes and the antibiotics were consistent with those reported between free d-Ala-d-Ala and the antibiotics in the literature. The assay is highly reproducible and selective toward glycopeptide antibiotics. Its detection limit and work concentration range are 0.5 microM and 0.5-4 microM for vancomycin, 0.25 microM and 0.25-2 microM for teicoplanin, and 1 microM and 1-8 microM for telavancin. Furthermore, we compared our assay in parallel with a commercial fluorescence polarization immunoassay (FPIA) kit in detecting teicoplanin spiked in human blood samples. The accuracy and precision of the two methods are comparable. We expect our assay to be useful in both research and clinical laboratories.

Two-Dimensional MoS2-Based Zwitterionic Hydrophilic Interaction Liquid Chromatography Material for the Specific Enrichment of Glycopeptides.

PubMed

Xia, Chaoshuang; Jiao, Fenglong; Gao, Fangyuan; Wang, Heping; Lv, Yayao; Shen, Yehua; Zhang, Yangjun; Qian, Xiaohong

2018-06-05

Mass spectrometry (MS)-based glycoproteomics research requires highly efficient sample preparation to eliminate interference from non-glycopeptides and to improve the efficiency of glycopeptide detection. In this work, a novel MoS 2 /Au-NP (gold nanoparticle)-L-cysteine nanocomposite was prepared for glycopeptide enrichment. The two-dimensional (2D) structured MoS 2 nanosheets served as a matrix that could provide a large surface area for immobilizing hydrophilic groups (such as L-cysteine) with low steric hindrance between the materials and the glycopeptides. As a result, the novel nanomaterial possessed an excellent ability to capture glycopeptides. Compared to commercial zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) materials, the novel nanomaterials exhibited excellent enrichment performance with ultrahigh selectivity and sensitivity (approximately 10 fmol), high binding capacity (120 mg g -1 ), high enrichment recovery (more than 93%), satisfying batch-to-batch reproducibility, and good universality for glycopeptide enrichment. In addition, its outstanding specificity and efficiency for glycopeptide enrichment was confirmed by the detection of glycopeptides from an human serum immunoglobulin G (IgG) tryptic digest in quantities as low as a 1:1250 molar ratio of IgG tryptic digest to bovine serum albumin tryptic digest. The novel nanocomposites were further used for the analysis of complex samples, and 1920 glycopeptide backbones from 775 glycoproteins were identified in three replicate analyses of 50 μg of proteins extracted from HeLa cell exosomes. The resulting highly informative mass spectra indicated that this multifunctional nanomaterial-based enrichment method could be used as a promising tool for the in-depth and comprehensive characterization of glycoproteomes in MS-based glycoproteomics.

Automatic and rapid identification of glycopeptides by nano-UPLC-LTQ-FT-MS and proteomic search engine.

PubMed

Giménez, Estela; Gay, Marina; Vilaseca, Marta

2017-01-30

Here we demonstrate the potential of nano-UPLC-LTQ-FT-MS and the Byonic™ proteomic search engine for the separation, detection, and identification of N- and O-glycopeptide glycoforms in standard glycoproteins. The use of a BEH C18 nanoACQUITY column allowed the separation of the glycopeptides present in the glycoprotein digest and a baseline-resolution of the glycoforms of the same glycopeptide on the basis of the number of sialic acids. Moreover, we evaluated several acquisition strategies in order to improve the detection and characterization of glycopeptide glycoforms with the maximum number of identification percentages. The proposed strategy is simple to set up with the technology platforms commonly used in proteomic labs. The method allows the straightforward and rapid obtention of a general glycosylated map of a given protein, including glycosites and their corresponding glycosylated structures. The MS strategy selected in this work, based on a gas phase fractionation approach, led to 136 unique peptides from four standard proteins, which represented 78% of the total number of peptides identified. Moreover, the method does not require an extra glycopeptide enrichment step, thus preventing the bias that this step could cause towards certain glycopeptide species. Data are available via ProteomeXchange with identifier PXD003578. We propose a simple and high-throughput glycoproteomics-based methodology that allows the separation of glycopeptide glycoforms on the basis of the number of sialic acids, and their automatic and rapid identification without prior knowledge of protein glycosites or type and structure of the glycans. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a data independent acquisition mass spectrometry workflow to enable glycopeptide analysis without predefined glycan compositional knowledge.

PubMed

Lin, Chi-Hung; Krisp, Christoph; Packer, Nicolle H; Molloy, Mark P

2018-02-10

Glycoproteomics investigates glycan moieties in a site specific manner to reveal the functional roles of protein glycosylation. Identification of glycopeptides from data-dependent acquisition (DDA) relies on high quality MS/MS spectra of glycopeptide precursors and often requires manual validation to ensure confident assignments. In this study, we investigated pseudo-MRM (MRM-HR) and data-independent acquisition (DIA) as alternative acquisition strategies for glycopeptide analysis. These approaches allow data acquisition over the full MS/MS scan range allowing data re-analysis post-acquisition, without data re-acquisition. The advantage of MRM-HR over DDA for N-glycopeptide detection was demonstrated from targeted analysis of bovine fetuin where all three N-glycosylation sites were detected, which was not the case with DDA. To overcome the duty cycle limitation of MRM-HR acquisition needed for analysis of complex samples such as plasma we trialed DIA. This allowed development of a targeted DIA method to identify N-glycopeptides without pre-defined knowledge of the glycan composition, thus providing the potential to identify N-glycopeptides with unexpected structures. This workflow was demonstrated by detection of 59 N-glycosylation sites from 41 glycoproteins from a HILIC enriched human plasma tryptic digest. 21 glycoforms of IgG1 glycopeptides were identified including two truncated structures that are rarely reported. We developed a data-independent mass spectrometry workflow to identify specific glycopeptides from complex biological mixtures. The novelty is that this approach does not require glycan composition to be pre-defined, thereby allowing glycopeptides carrying unexpected glycans to be identified. This is demonstrated through the analysis of immunoglobulins in human plasma where we detected two IgG1 glycoforms that are rarely observed. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of Sialic Acid Linkages on Intact Glycopeptides via Differential Chemical Modification Using IntactGIG-HILIC

NASA Astrophysics Data System (ADS)

Yang, Shuang; Wu, Wells W.; Shen, Rong-Fong; Bern, Marshall; Cipollo, John

2018-04-01

Mass spectrometric analysis of intact glycopeptides can reveal detailed information about glycosite, glycan structural features, and their heterogeneity. Sialyl glycopeptides can be positively, negatively, or neutrally charged depending on pH of their buffer solution and ionization conditions. To detect sialoglycopeptides, a negative-ion mode mass spectrometry may be applied with a minimal loss of sialic acids, although the positively charged or neutral glycopeptides may be excluded. Alternatively, the sialyl glycopeptides can be identified using positive-ion mode analysis by doping a high concentration of sodium salts to the analytes. Although manipulation of unmodified sialoglycopeptides can be useful for analysis of samples, less than optimal ionization, facile loss of sialyl and unfavorable ionization of accompanying non-sialyl peptides make such strategies suboptimal. Currently available chemical derivatization methods, while stabilizing for sialic acid, mask sialic acid linkage configuration. Here, we report the development of a novel approach to neutralize sialic acids via sequentially chemical modification that also reveals their linkage configuration, often an important determinant in biological function. This method utilizes several components to facilitate glycopeptide identification. These include the following: solid phase derivatization, enhanced ionization of sialoglycopeptides, differentiation of sialic acid linkage, and enrichment of the modified glycopeptides by hydrophilic interaction liquid chromatography. This technology can be used as a tool for quantitative analysis of protein sialylation in diseases with determination of sialic acid linkage configuration. [Figure not available: see fulltext.

[Emergence of glycopeptide resistant Enterococcus faecium in Algeria: a case report].

PubMed

Hamidi, Moufida; Ammari, Houria; Ghaffor, Mohamed; Benamrouche, Nabila; Tali-Maamar, Hassiba; Tala-Khir, Farida; Younsi, Mokhtar; Rahal, Kheira

2013-01-01

A glycopeptide-resistant Enterococcus faecium (EFRG) was isolated from a wound in a patient hospitalized in a university hospital in Algiers. This strain was resistant to several antibiotics. This patient was carrying this strain in the digestive tract which may partly explain its origin. Genotypic comparison of the two strains by pulsed field gel electrophoresis showed that it was the same strain. Glycopeptide resistance was due to the presence of the vanA gene. Vigilance is required facing the emergence of strains of EFRG in our hospitals.

Comparative activity of tedizolid and glycopeptide combination therapies for the treatment of Staphylococcus aureus infections: an in vitro and in vivo evaluation against strains with reduced susceptibility to glycopeptides.

PubMed

Betts, J W; Abdul Momin, H F; Phee, L M; Wareham, D W

2018-02-01

Glycopeptides are widely used for the treatment of meticillin-resistant Staphylococcus aureus (MRSA) infections. Although difficult to detect, isolates with reduced (GISA), hetero (hGISA) or complete (GRSA) resistance to glycopeptides are increasingly reported. Optimal therapy for such strains is unknown. We compared the in vitro and in vivo activity of tedizolid (TED), a recently licensed oxazolidonone, with vancomycin (VAN) and teicoplanin (TEIC) combined with fusidic acid (FD) or rifampicin (RIF) against S. aureus (SA) with reduced susceptibility to glycopeptides. Susceptibility was determined for six (GISA, hGISA and GRSA) reference strains and 72 clinical MRSA isolates screened for hGISA/GISA-like phenotypes. Synergy and bactericidal activity were assessed using chequerboard and time-kill assays. The G. mellonella wax moth caterpillar model was used to measure the activity of TED and the combinations in vivo. Glycopeptide MICs (VAN/TEIC) ranged from 0.5-8/4 and 0.125-1 for TED. No significant synergy was noted when VAN/TEIC were combined with either RIF or FD. Time-kill assays confirmed that TED was bacteriostatic but superior to VAN and TEIC against GISA strains. In G. mellonella TED was more effective than TEIC monotherapy versus GISA strains. The combination of TEIC with RIF was the most effective combination overall, both in vitro and in vivo. TED had good in vitro activity versus MRSA including those with reduced susceptibility to glycopeptides. Although bacteriostatic, it was effective in the G. mellonella model and superior to TEIC in the treatment of GISA. Although this supports the use of TED for MRSA and GISA, the TEIC/RIF combination also warrants further study.

Sulfated Glycopeptide Nanostructures for Multipotent Protein Activation

PubMed Central

Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng; Álvarez, Zaida; Sleep, Eduard; Chun, Danielle S.; Weiner, Joseph A.; Cook, Ralph W.; Freshman, Ryan D.; Schallmo, Michael S.; Katchko, Karina M.; Schneider, Andrew D.; Smith, Justin T.; Yun, Chawon; Singh, Gurmit; Hashmi, Sohaib Z.; McClendon, Mark T.; Yu, Zhilin; Stock, Stuart R.; Hsu, Wellington K.; Hsu, Erin L.; Stupp, Samuel I.

2017-01-01

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with very different polysaccharide binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signaling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than expected. These super-bioactive nanostructures may enable many therapies in the horizon involving proteins. PMID:28650443

Structure and Function of the Glycopeptide N-methyltransferase MtfA, a Tool for the Biosynthesis of Modified Glycopeptide Antibiotics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Rong; Lamb, Sherry S.; Zakeri, Bijan

2009-06-01

There is a considerable interest in the modification of existing antibiotics to generate new antimicrobials. Glycopeptide antibiotics (GPAs) are effective against serious Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus. However, resistance to these antibiotics is becoming a serious problem requiring new strategies. We show that the Amycolatopsis orientalis (S)-adenosyl-L-methionine-dependent methyltransferase MtfA, from the vancomycin-class GPA chloroeremomycin biosynthetic pathway, catalyzes in vivo and in vitro methyl transfer to generate methylated GPA derivatives of the teicoplanin class. The crystal structure of MtfA complexed with (S)-adenosyl-L-methionine, (S)-adenosylhomocysteine, or sinefungin inhibitor, coupled with mutagenesis, identified His228 as a likely general base required for methylmore » transfer to the N terminus of the glycopeptide. Computational docking and molecular dynamics simulations were used to model binding of demethyl-vancomycin aglycone to MtfA. These results demonstrate its utility as a tool for engineering methylated analogs of GPAs.« less

Status Report on the High-Throughput Characterization of Complex Intact O-Glycopeptide Mixtures

NASA Astrophysics Data System (ADS)

Pap, Adam; Klement, Eva; Hunyadi-Gulyas, Eva; Darula, Zsuzsanna; Medzihradszky, Katalin F.

2018-05-01

A very complex mixture of intact, human N- and O-glycopeptides, enriched from the tryptic digest of urinary proteins of three healthy donors using a two-step lectin affinity enrichment, was analyzed by LC-MS/MS, leading to approximately 45,000 glycopeptide EThcD spectra. Two search engines, Byonic and Protein Prospector, were used for the interpretation of the data, and N- and O-linked glycopeptides were assigned from separate searches. The identification rate was very low in all searches, even when results were combined. Thus, we investigated the reasons why was it so, to help to improve the identification success rate. Focusing on O-linked glycopeptides, we noticed that in EThcD, larger glycan oxonium ions better survive the activation than those in HCD. These fragments, combined with reducing terminal Y ions, provide important information about the glycan(s) present, so we investigated whether filtering the peaklists for glycan oxonium ions indicating the presence of a tetra- or hexasaccharide structure would help to reveal all molecules containing such glycans. Our study showed that intact glycans frequently do not survive even mild supplemental activation, meaning one cannot rely on these oxonium ions exclusively. We found that ETD efficiency is still a limiting factor, and for highly glycosylated peptides, the only information revealed in EThcD was related to the glycan structures. The limited overlap of results delivered by the two search engines draws attention to the fact that automated data interpretation of O-linked glycopeptides is not even close to being solved. [Figure not available: see fulltext.

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

NASA Astrophysics Data System (ADS)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

Biomedicine of Enkephalin-Derived Glycopeptide Analgesics

NASA Astrophysics Data System (ADS)

Polt, Robin

The incorporation of glycosides into peptide neurotransmitters imparts drug-like character to the neurotransmitter "message" via "membrane hopping". The importance of the glycopeptide-membrane interaction is emphasized, and the biousian theory is briefly explained. Application of this approach to enkephalins, the endogenous opioid peptides, leads to potent analgesic compounds capable of systemic delivery. The clinical applications of these compounds are advocated by the author.

Exploring Site-Specific N-Glycosylation Microheterogeneity of Haptoglobin using Glycopeptide CID Tandem Mass Spectra and Glycan Database Search

PubMed Central

Chandler, Kevin Brown; Pompach, Petr; Goldman, Radoslav

2013-01-01

Glycosylation is a common protein modification with a significant role in many vital cellular processes and human diseases, making the characterization of protein-attached glycan structures important for understanding cell biology and disease processes. Direct analysis of protein N-glycosylation by tandem mass spectrometry of glycopeptides promises site-specific elucidation of N-glycan microheterogeneity, something which detached N-glycan and de-glycosylated peptide analyses cannot provide. However, successful implementation of direct N-glycopeptide analysis by tandem mass spectrometry remains a challenge. In this work, we consider algorithmic techniques for the analysis of LC-MS/MS data acquired from glycopeptide-enriched fractions of enzymatic digests of purified proteins. We implement a computational strategy which takes advantage of the properties of CID fragmentation spectra of N-glycopeptides, matching the MS/MS spectra to peptide-glycan pairs from protein sequences and glycan structure databases. Significantly, we also propose a novel false-discovery-rate estimation technique to estimate and manage the number of false identifications. We use a human glycoprotein standard, haptoglobin, digested with trypsin and GluC, enriched for glycopeptides using HILIC chromatography, and analyzed by LC-MS/MS to demonstrate our algorithmic strategy and evaluate its performance. Our software, GlycoPeptideSearch (GPS), assigned glycopeptide identifications to 246 of the spectra at false-discovery-rate 5.58%, identifying 42 distinct haptoglobin peptide-glycan pairs at each of the four haptoglobin N-linked glycosylation sites. We further demonstrate the effectiveness of this approach by analyzing plasma-derived haptoglobin, identifying 136 N-linked glycopeptide spectra at false-discovery-rate 0.4%, representing 15 distinct glycopeptides on at least three of the four N-linked glycosylation sites. The software, GlycoPeptideSearch, is available for download from http

Targeted, Site-specific quantitation of N- and O-glycopeptides using 18O-labeling and product ion based mass spectrometry.

PubMed

Srikanth, Jandhyam; Agalyadevi, Rathinasamy; Babu, Ponnusamy

2017-02-01

The site-specific quantitation of N- and O-glycosylation is vital to understanding the function(s) of different glycans expressed at a given site of a protein under physiological and disease conditions. Most commonly used precursor ion intensity based quantification method is less accurate and other labeled methods are expensive and require enrichment of glycopeptides. Here, we used glycopeptide product (y and Y0) ions and 18 O-labeling of C-terminal carboxyl group as a strategy to obtain quantitative information about fold-change and relative abundance of most of the glycoforms attached to the glycopeptides. As a proof of concept, the accuracy and robustness of this targeted, relative quantification LC-MS method was demonstrated using Rituximab. Furthermore, the N-glycopeptide quantification results were compared with a biosimilar of Rituximab and validated with quantitative data obtained from 2-AB-UHPLC-FL method. We further demonstrated the intensity fold-change and relative abundance of 46 unique N- and O-glycopeptides and aglycopeptides from innovator and biosimilar samples of Etanercept using both the normal-MS and product ion based quantitation. The results showed a very similar site-specific expression of N- and O-glycopeptides between the samples but with subtle differences. Interestingly, we have also been able to quantify macro-heterogeneity of all N- and O-glycopetides of Etanercept. In addition to applications in biotherapeutics, the developed method can also be used for site-specific quantitation of N- and O-glycopeptides and aglycopeptides of glycoproteins with known glycosylation pattern.

[Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides].

PubMed

Sun, Xudong; Zhang, Lingyi; Zhang, Weibing

2017-07-08

Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO 2 ). The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N -linked glycopeptides. The Cys-Mal@SiO 2 demonstrated better identification capability over Cys@SiO 2 , Mal@SiO 2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO 2 . In addition, 1551 unique glycopeptides with 906 N -glycosylation sites from 466 different N -linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO 2 . In contrast, the numbers of identified glycopeptides, glycoproteins and N -glycosylation sites identified by Cys@SiO 2 were 211, 67, 127 respectively less than by Cys-Mal@SiO 2 , and the corresponding numbers were 289, 76, 193 by Mal@SiO 2 . These results showed that the developed Cys-Mal@SiO 2 is a promising affinity material for N -glycoproteomics research of real complex biological samples.

A review of the current place of glycopeptides in turkish medical practice

PubMed Central

Erdem, Hakan; Oncul, Oral

2007-01-01

Background: Glycopeptide antibiotics are considered by many investigators to be the last resort in the treatment of gram-positive bacterial infections. Objective: The aim of this review was to assess the place of glycopeptides in the treatment of common gram-positive bacteria in accordance with the current epidemiologic data in Turkey. Methods: A search of both the English- and Turkish-language literature indexed on MEDLINE, Ulakbim (Turkey), and Pleksus (Turkey) was performed using the terms: vancomycin, teicoplanin, and glycopeptides, or their Turkish-language counterparts. The complete texts of the articles found in these databases were obtained from the electronic library of Gulhane Medical Academy, Ankara, Turkey. Articles from regional journals, without the support of an electronic format, were obtained by direct communication. Articles of interest were those based on studies occurring in Turkish populations, with special consideration given to publications in press after 2002. Results: Staphylococci were the most frequent gram-positive pathogens encountered in Turkish hospitals. Studies have found that ∼74% of strains were Staphylococcus aureus and the remaining strains were coagulase-negative staphylococci (CoNS). Overall methicillin resistance in staphylococci was reported as ∼60%. In Turkey, S aureus was one of the most common infectious agents found inside hospitals and is deemed a growing threat in the community. While the rate of methicillin resistance in community-acquired isolates is ∼4%, the data from hospitals suggest that reduced resistance comprises most of the isolates. In the studies reviewed, older quinolones like ciprofloxacin and ofloxacin seem to be ineffective in nearly half of the S aureus isolates. Alternatives like rifampicin, gentamicin, tetracycline, trimethoprim/sulfamethoxazole (TMP/SMX), clindamycin, and erythromycin have had substantial resistance profiles in >50% of the strains. In recent Turkish studies, in vitro profiles

pGlyco 2.0 enables precision N-glycoproteomics with comprehensive quality control and one-step mass spectrometry for intact glycopeptide identification.

PubMed

Liu, Ming-Qi; Zeng, Wen-Feng; Fang, Pan; Cao, Wei-Qian; Liu, Chao; Yan, Guo-Quan; Zhang, Yang; Peng, Chao; Wu, Jian-Qiang; Zhang, Xiao-Jin; Tu, Hui-Jun; Chi, Hao; Sun, Rui-Xiang; Cao, Yong; Dong, Meng-Qiu; Jiang, Bi-Yun; Huang, Jiang-Ming; Shen, Hua-Li; Wong, Catherine C L; He, Si-Min; Yang, Peng-Yuan

2017-09-05

The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification. The N-glycoproteome of samples metabolically labeled with 15 N/ 13 C were analyzed quantitatively and utilized to validate the glycopeptide identification, which could be used as a novel benchmark pipeline to compare different search engines. Finally, we report a large-scale glycoproteome dataset consisting of 10,009 distinct site-specific N-glycans on 1988 glycosylation sites from 955 glycoproteins in five mouse tissues.Protein glycosylation is a heterogeneous post-translational modification that generates greater proteomic diversity that is difficult to analyze. Here the authors describe pGlyco 2.0, a workflow for the precise one step identification of intact N-glycopeptides at the proteome scale.

Large-scale identification of core-fucosylated glycopeptide sites in pancreatic cancer serum using mass spectrometry.

PubMed

Tan, Zhijing; Yin, Haidi; Nie, Song; Lin, Zhenxin; Zhu, Jianhui; Ruffin, Mack T; Anderson, Michelle A; Simeone, Diane M; Lubman, David M

2015-04-03

Glycosylation has significant effects on protein function and cell metastasis, which are important in cancer progression. It is of great interest to identify site-specific glycosylation in search of potential cancer biomarkers. However, the abundance of glycopeptides is low compared to that of nonglycopeptides after trypsin digestion of serum samples, and the mass spectrometric signals of glycopeptides are often masked by coeluting nonglycopeptides due to low ionization efficiency. Selective enrichment of glycopeptides from complex serum samples is essential for mass spectrometry (MS)-based analysis. Herein, a strategy has been optimized using LCA enrichment to improve the identification of core-fucosylation (CF) sites in serum of pancreatic cancer patients. The optimized strategy was then applied to analyze CF glycopeptide sites in 13 sets of serum samples from pancreatic cancer, chronic pancreatitis, healthy controls, and a standard reference. In total, 630 core-fucosylation sites were identified from 322 CF proteins in pancreatic cancer patient serum using an Orbitrap Elite mass spectrometer. Further data analysis revealed that 8 CF peptides exhibited a significant difference between pancreatic cancer and other controls, which may be potential diagnostic biomarkers for pancreatic cancer.

Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis.

PubMed

Huang, Junfeng; Wan, Hao; Yao, Yating; Li, Jinan; Cheng, Kai; Mao, Jiawei; Chen, Jin; Wang, Yan; Qin, Hongqiang; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-10-20

Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold.

Glycopeptide Susceptibility Profiles of Staphylococcus haemolyticus Bloodstream Isolates

PubMed Central

Biavasco, Francesca; Vignaroli, Carla; Lazzarini, Raffaella; Varaldo, Pietro E.

2000-01-01

Twelve clinical strains of Staphylococcus haemolyticus (eight methicillin resistant and three methicillin susceptible), isolated from blood cultures between 1982 and 1997, were investigated for teicoplanin and vancomycin susceptibility profiles. On the basis of conventional MIC tests and breakpoints, four isolates were susceptible (MICs, 1 to 8 μg/ml) and eight were resistant (MICs, 32 to 64 μg/ml) to teicoplanin while all were susceptible to vancomycin (MICs, 1 to 2 μg/ml). All four strains for which the conventional teicoplanin MICs were within the range of susceptibility expressed heterogeneous resistance to teicoplanin and homogeneous vancomycin susceptibility. Of the eight strains for which the conventional teicoplanin MICs were within the range of resistance, six expressed heterogeneous and two expressed homogeneous teicoplanin resistance while seven showed heterogeneous vancomycin resistance profiles (with subpopulations growing on 8 μg of the drug per ml at frequencies of ≥10−6 for six strains and 10−7 for one) and one demonstrated homogeneous vancomycin susceptibility. Of six bloodstream isolates of other staphylococcal species (S. aureus, S. epidermidis, and S. simulans), for all of which the conventional teicoplanin MICs were ≥4 μg/ml and the vancomycin MICs were ≤2 μg/ml, none exhibited heterogeneous susceptibility profiles for teicoplanin while three showed homogeneous and three showed heterogeneous susceptibility profiles for vancomycin (with subpopulations growing on 8 μg of the drug per ml found for only one strain). The results of this study indicate that a heterogeneous response to glycopeptides is a common feature of S. haemolyticus isolates and suggest that susceptibility to glycopeptides as determined by conventional MIC tests may not be predictive of the outcome of glycopeptide therapy. PMID:11036034

Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides.

PubMed

Wang, Jiawen; Yao, Jizong; Sun, Nianrong; Deng, Chunhui

2017-08-25

As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe 3 O 4 @TiO 2 @PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe 3 O 4 @TiO 2 @PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe 3 O 4 @TiO 2 @PEG nanomaterials for glycoproteomic research. Copyright © 2017 Elsevier B.V. All rights reserved.

An accessible protocol for solid-phase extraction of N-linked glycopeptides through reductive amination by amine-functionalized magnetic nanoparticles.

PubMed

Zhang, Ying; Kuang, Min; Zhang, Lijuan; Yang, Pengyuan; Lu, Haojie

2013-06-04

In light of the significance of glycosylation for wealthy biological events, it is important to prefractionate glycoproteins/glycopeptides from complex biological samples. Herein, we reported a novel protocol of solid-phase extraction of glycopeptides through a reductive amination reaction by employing the easily accessible 3-aminopropyltriethoxysilane (APTES)-functionalized magnetic nanoparticles. The amino groups from APTES, which were assembled onto the surface of the nanoparticles through a one-step silanization reaction, could conjugate with the aldehydes from oxidized glycopeptides and, therefore, completed the extraction. To the best of our knowledge, this is the first example of applying the reductive amination reaction into the isolation of glycopeptides. Due to the elimination of the desalting step, the detection limit of glycopeptides was improved by 2 orders of magnitude, compared to the traditional hydrazide chemistry-based solid phase extraction, while the extraction time was shortened to 4 h, suggesting the high sensitivity, specificity, and efficiency for the extraction of N-linked glycopeptides by this method. In the meantime, high selectivity toward glycoproteins was also observed in the separation of Ribonuclease B from the mixtures contaminated with bovine serum albumin. What's more, this technique required significantly less sample volume, as demonstrated in the successful mapping of glycosylation of human colorectal cancer serum with the sample volume as little as 5 μL. Because of all these attractive features, we believe that the innovative protocol proposed here will shed new light on the research of glycosylation profiling.

A40926, a new glycopeptide antibiotic with anti-Neisseria activity.

PubMed Central

Goldstein, B P; Selva, E; Gastaldo, L; Berti, M; Pallanza, R; Ripamonti, F; Ferrari, P; Denaro, M; Arioli, V; Cassani, G

1987-01-01

In the course of a search for glycopeptide antibiotics having novel biological properties, we isolated A40926. Produced by an actinomycete of the genus Actinomadura, A40926 is a complex of four main factors which contain a fatty acid as part of a glycolipid attached to the peptide backbone. Its activity was, in most respects, similar to that of other glycopeptides, such as vancomycin and teicoplanin. However, in addition to inhibiting gram-positive bacteria, A40926 was very active against Neisseria gonorrhoeae. A40926 was rapidly bactericidal for N. gonorrhoeae clinical isolates at concentrations equal to or slightly higher than the MIC. In mice, levels in serum were higher and more prolonged than those of an equivalent subcutaneous dose of teicoplanin. These properties suggest that A40926 may have potential in the therapy of gonorrhea. PMID:2964225

Homoserine as an Aspartic Acid Precursor for Synthesis of Proteoglycan Glycopeptide Containing Aspartic Acid and a Sulfated Glycan Chain.

PubMed

Yang, Weizhun; Ramadan, Sherif; Yang, Bo; Yoshida, Keisuke; Huang, Xuefei

2016-12-02

Among many hurdles in synthesizing proteoglycan glycopeptides, one challenge is the incorporation of aspartic acid in the peptide backbone and acid sensitive O-sulfated glycan chains. To overcome this, a new strategy was developed utilizing homoserine as an aspartic acid precursor. The conversion of homoserine to aspartic acid in the glycopeptide was successfully accomplished by late stage oxidation using (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO) and bis(acetoxy)iodobenzene (BAIB). This is the first time that a glycopeptide containing aspartic acid and an O-sulfated glycan was synthesized.

Extracting Both Peptide Sequence and Glycan Structural Information by 157 nm Photodissociation of N-Linked Glycopeptides

PubMed Central

Zhang, Liangyi; Reilly, James P.

2009-01-01

157 nm photodissociation of N-linked glycopeptides was investigated in MALDI tandem time-of-flight (TOF) and linear ion trap mass spectrometers. Singly-charged glycopeptides yielded abundant peptide and glycan fragments. The peptide fragments included a series of x-, y-, v- and w- ions with the glycan remaining intact. These provide information about the peptide sequence and the glycosylation site. In addition to glycosidic fragments, abundant cross-ring glycan fragments that are not observed in low-energy CID were detected. These fragments provide insight into the glycan sequence and linkages. Doubly-charged glycopeptides generated by nanospray in the linear ion trap mass spectrometer also yielded peptide and glycan fragments. However, the former were dominated by low-energy fragments such as b- and y- type ions while glycan was primarily cleaved at glycosidic bonds. PMID:19113943

Distinctive and Complementary MS2 Fragmentation Characteristics for Identification of Sulfated Sialylated N-Glycopeptides by nanoLC-MS/MS Workflow

NASA Astrophysics Data System (ADS)

Kuo, Chu-Wei; Guu, Shih-Yun; Khoo, Kay-Hooi

2018-04-01

High sensitivity identification of sulfated glycans carried on specific sites of glycoproteins is an important requisite for investigation of molecular recognition events involved in diverse biological processes. However, aiming for resolving site-specific glycosylation of sulfated glycopeptides by direct LC-MS2 sequencing is technically most challenging. Other than the usual limiting factors such as lower abundance and ionization efficiency compared to analysis of non-glycosylated peptides, confident identification of sulfated glycopeptides among the more abundant non-sulfated glycopeptides requires additional considerations in the selective enrichment and detection strategies. Metal oxide has been applied to enrich phosphopeptides and sialylated glycopeptides, but its use to capture sulfated glycopeptides has not been investigated. Likewise, various complementary MS2 fragmentation modes have yet to be tested against sialylated and non-sialylated sulfoglycopeptides due to limited appropriate sample availability. In this study, we have investigated the feasibility of sequencing tryptic sulfated N-glycopeptide and its MS2 fragmentation characteristics by first optimizing the enrichment methods to allow efficient LC-MS detection and MS2 analysis by a combination of CID, HCD, ETD, and EThcD on hybrid and tribrid Orbitrap instruments. Characteristic sulfated glyco-oxonium ions and direct loss of sulfite from precursors were detected as evidences of sulfate modification. It is anticipated that the technical advances demonstrated in this study would allow a feasible extension of our sulfoglycomic analysis to sulfoglycoproteomics. [Figure not available: see fulltext.

Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides

NASA Astrophysics Data System (ADS)

Chen, Yajing; Xiong, Zhichao; Zhang, Lingyi; Zhao, Jiaying; Zhang, Quanqing; Peng, Li; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-02-01

Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g-1), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have

Complex Regulatory Networks Governing Production of the Glycopeptide A40926.

PubMed

Alduina, Rosa; Sosio, Margherita; Donadio, Stefano

2018-04-05

Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus . A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis . This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoB R , have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain.

Isolation of N-linked glycopeptides by hydrazine-functionalized magnetic particles.

PubMed

Sun, Shisheng; Yang, Ganglong; Wang, Ting; Wang, Qinzhe; Chen, Chao; Li, Zheng

2010-04-01

We introduce a novel combination of magnetic particles with hydrazine chemistry, dubbed as hydrazine-functionalized magnetic particles (HFMP) for isolation of glycopeptides. Four methods have been developed and compared for the production of HFMP by hydrazine modification of the surface of the carboxyl and epoxy-silanized magnetic particles, respectively. The evaluation of the capability and specificity of HFMP as well as the optimization of the coupling condition for capturing of glycoproteins were systematically investigated. The results showed that HFMP prepared by adipic dihydrazide functionalization from carboxyl-silanized magnetic particles (HFCA) displayed the maximum capture capacity and isolated efficiency for glycoprotein. When measured with glycoproteins, the capacity of the HFCA (1 g) for coupling bovine fetuin was 130 +/- 5.3 mg. The capability of this method was also confirmed by successful isolation of all formerly glycosylated peptides from standard glycoproteins and identification of their glycosylation sites, which demonstrated the feasibility of the HFCA as an alternative solid support for isolation of glycoproteins/glycopeptides.

Site-specific N-glycosylation analysis: matrix-assisted laser desorption/ionization quadrupole-quadrupole time-of-flight tandem mass spectral signatures for recognition and identification of glycopeptides.

PubMed

Krokhin, Oleg; Ens, Werner; Standing, Kenneth G; Wilkins, John; Perreault, Hélène

2004-01-01

The identification of glycosylation sites in proteins is often possible through a combination of proteolytic digestion, separation, mass spectrometry (MS) and tandem MS (MS/MS). Liquid chromatography (LC) in combination with MS/MS has been a reliable method for detecting glycopeptides in digestion mixtures, and for assigning glycosylation sites and glycopeptide sequences. Direct interfacing of LC with MS relies on electrospray ionization, which produces ions with two, three or four charges for most proteolytic peptides and glycopeptides. MS/MS spectra of such glycopeptide ions often lead to ambiguous interpretation if deconvolution to the singly charged level is not used. In contrast, the matrix-assisted laser desorption/ionization (MALDI) technique usually produces singly charged peptide and glycopeptide ions. These ions require an extended m/z range, as provided by the quadrupole-quadrupole time-of-flight (QqTOF) instrument used in these experiments, but the main advantages of studying singly charged ions are the simplicity and consistency of the MS/MS spectra. A first aim of the present study is to develop methods to recognize and use glycopeptide [M+H]+ ions as precursors for MS/MS, and thus for glycopeptide/glycoprotein identification as part of wider proteomics studies. Secondly, this article aims at demonstrating the usefulness of MALDI-MS/MS spectra of N-glycopeptides. Mixtures of diverse types of proteins, obtained commercially, were prepared and subjected to reduction, alkylation and tryptic digestion. Micro-column reversed-phase separation allowed deposition of several fractions on MALDI plates, followed by MS and MS/MS analysis of all peptides. Glycopeptide fractions were identified after MS by their specific m/z spacing patterns (162, 203, 291 u) between glycoforms, and then analyzed by MS/MS. In most cases, MS/MS spectra of [M+H]+ ions of glycopeptides featured peaks useful for determining sugar composition, peptide sequence, and thus probable

Convergent Synthesis of N-Linked Glycopeptides via Aminolysis of ω-Asp p-Nitrophenyl Thioesters in Solution.

PubMed

Du, Jing-Jing; Gao, Xiao-Fei; Xin, Ling-Ming; Lei, Ze; Liu, Zheng; Guo, Jun

2016-10-07

An efficient N-linked glycosylation reaction between glycosylamines and p-nitrophenyl thioester peptides has been developed. The reaction conditions are mild and compatible with the C-terminal free carboxylic acid group and the unprotected N-linked sialyloligosaccharide. By means of this convergent strategy, a versatile N-glycopeptide fragment containing an N-terminal Thz and a C-terminal thioester was readily prepared, which is available for the synthesis of long glycopeptides and glycoproteins using the protocol of native chemical ligation.

Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides.

PubMed

Chen, Yajing; Xiong, Zhichao; Zhang, Lingyi; Zhao, Jiaying; Zhang, Quanqing; Peng, Li; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-02-21

Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.

Validation of VITEK 2 Version 4.01 Software for Detection, Identification, and Classification of Glycopeptide-Resistant Enterococci

PubMed Central

Abele-Horn, Marianne; Hommers, Leif; Trabold, René; Frosch, Matthias

2006-01-01

We evaluated the ability of the new VITEK 2 version 4.01 software to identify and detect glycopeptide-resistant enterococci compared to that of the reference broth microdilution method and to classify them into the vanA, vanB, vanC1, and vanC2 genotypes. Moreover, the accuracy of antimicrobial susceptibility testing with agents with improved potencies against glycopeptide-resistant enterococci was determined. A total of 121 enterococci were investigated. The new VITEK 2 software was able to identify 114 (94.2%) enterococcal strains correctly to the species level and to classify 119 (98.3%) enterococci correctly to the glycopeptide resistance genotype level. One Enterococcus casseliflavus strain and six Enterococcus faecium vanA strains with low-level resistance to vancomycin were identified with low discrimination, requiring additional tests. One of the vanA strains was misclassified as the vanB type, and one glycopeptide-susceptible E. facium wild type was misclassified as the vanA type. The overall essential agreements for antimicrobial susceptibility testing results were 94.2% for vancomycin, 95.9% for teicoplanin, 100% for quinupristin-dalfopristin and moxifloxacin, and 97.5% for linezolid. The rates of minor errors were 9% for teicoplanin and 5% for the other antibiotic agents. The identification and susceptibility data were produced within 4 h to 6 h 30 min and 8 h 15 min to 12 h 15 min. In conclusion, use of VITEK 2 version 4.01 software appears to be a reliable method for the identification and detection of glycopeptide-resistant enterococci as well as an improvement over the use of the former VITEK 2 database. However, a significant reduction in the detection time would be desirable. PMID:16390951

Analysis of PNGase F-resistant N-glycopeptides using SugarQb for Proteome Discoverer 2.1 reveals cryptic substrate specificities.

PubMed

Stadlmann, Johannes; Hoi, David M; Taubenschmid, Jasmin; Mechtler, Karl; Penninger, Josef M

2018-05-18

SugarQb (www.imba.oeaw.ac.at/sugarqb) is a freely available collection of computational tools for the automated identification of intact glycopeptides from high-resolution HCD MS/MS data-sets in the Proteome Discoverer environment. We report the migration of SugarQb to the latest and free version of Proteome Discoverer 2.1, and apply it to the analysis of PNGase F-resistant N-glycopeptides from mouse embryonic stem cells. The analysis of intact glycopeptides highlights unexpected technical limitations to PNGase F-dependent glycoproteomic workflows at the proteome level, and warrants a critical re-interpretation of seminal data-sets in the context of N-glycosylation-site prediction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Rapid Endolysosomal Escape and Controlled Intracellular Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides and Glycopeptides.

PubMed

Tan, Roger S; Naruchi, Kentaro; Amano, Maho; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2015-09-18

A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment. Chemoselective ligation of the ketone-functionalized hexahistidine derivative facilitated both efficient endocytic entry and rapid endolysosomal escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human normal and cancer cells, while modifications of these QDs with cell-penetrating arginine-rich peptides showed poor cellular uptake and induced self-aggregation of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with serglycine-like glycopeptides, namely synthetic proteoglycan initiators (PGIs), elicited the entry and controlled intracellular trafficking, Golgi localization, and also excretion of these nanoparticles, which suggested that the present approach would provide an ideal platform for the design of high performance NDD systems.

Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization

NASA Astrophysics Data System (ADS)

Yu, Qing; Wang, Bowen; Chen, Zhengwei; Urabe, Go; Glover, Matthew S.; Shi, Xudong; Guo, Lian-Wang; Kent, K. Craig; Li, Lingjun

2017-09-01

Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. Subsequent experiments tested its utility for human plasma N-glycoproteins. Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. We also anticipate this approach can be readily applied to large-scale O-glycoproteome characterization. [Figure not available: see fulltext.

Glycopeptides versus β-lactams for the prevention of surgical site infections in cardiovascular and orthopedic surgery: a meta-analysis.

PubMed

Saleh, Anas; Khanna, Ashish; Chagin, Kevin M; Klika, Alison K; Johnston, Douglas; Barsoum, Wael K

2015-01-01

To compare the efficacy of glycopeptides and β-lactams in preventing surgical site infections (SSIs) in cardiac, vascular, and orthopedic surgery. The cost-effectiveness of switching from β-lactams to glycopeptides for preoperative antibiotic prophylaxis has been controversial. β-Lactams are generally recommended in clean surgical procedures, but they are ineffective against resistant gram-positive bacteria. PubMed, International Pharmaceuticals Abstracts, Scopus, and Cochrane were searched for randomized clinical trials comparing glycopeptides and β-lactams for prophylaxis in adults undergoing cardiac, vascular, or orthopedic surgery. Abstracts and conference proceedings were included. Two independent reviewers performed study selection, data extraction, and assessment of risk of bias. Fourteen studies with a total of 8952 patients were analyzed. No difference was detected in overall SSIs between antibiotic types. However, compared with β-lactams, glycopeptides reduced the risk of resistant staphylococcal SSIs by 48% (relative risk, 0.52; 95% confidence interval, 0.29-0.93; P = 0.03) and enterococcal SSIs by 64% (relative risk, 0.36; 95% confidence interval, 0.16-0.80; P = 0.01), but increased respiratory tract infections by 54% (relative risk, 1.54; 95% confidence interval, 1.19-2.01; P ≤ 0.01). Subgroup analysis of cardiac procedures showed superiority of β-lactams in preventing superficial and deep chest SSIs, susceptible staphylococcal SSIs, and respiratory tract infections. Glycopeptides reduce the risk of resistant staphylococcal SSIs and enterococcal SSIs, but increase the risk of respiratory tract infections. Additional high-quality randomized clinical trials are needed as these results are limited by high risk of bias.

Concurrent Automated Sequencing of the Glycan and Peptide Portions of O-Linked Glycopeptide Anions by Ultraviolet Photodissociation Mass Spectrometry

PubMed Central

Madsen, James A.; Ko, Byoung Joon; Xu, Hua; Iwashkiw, Jeremy A.; Robotham, Scott A.; Shaw, Jared B.; Feldman, Mario F.; Brodbelt, Jennifer S.

2013-01-01

O -glycopeptides are often acidic owing to the frequent occurrence of acidic saccharides in the glycan, rendering traditional proteomic workflows that rely on positive mode tandem mass spectrometry (MS/MS) less effective. In this report, we demonstrate the utility of negative mode ultraviolet photodissociation (UVPD) MS for the characterization of acidic O-linked glycopeptide anions. This method was evaluated for a series of singly- and multiply-deprotonated glycopeptides from the model glycoprotein kappa casein, resulting in production of both peptide and glycan product ions that afforded 100% sequence coverage of the peptide and glycan moieties from a single MS/MS event. The most abundant and frequent peptide sequence ions were a/x-type products, which, importantly, were found to retain the labile glycan modifications. The glycan-specific ions mainly arose from glycosidic bond cleavages (B, Y, C, and Z ions) in addition to some less common cross-ring cleavages. Based on the UVPD fragmentation patterns, an automated database searching strategy (based on the MassMatrix algorithm) was designed that is specific for the analysis of glycopeptide anions by UVPD. This algorithm was used to identify glycopeptides from mixtures of glycosylated and non-glycosylated peptides, sequence both glycan and peptide moieties simultaneously, and pinpoint the correct site(s) of glycosylation. This methodology was applied to uncover novel site-specificity of the O-linked glycosylated OmpA/MotB from the “superbug” A. baumannii to help aid in the elucidation of the functional role that protein glycosylation plays in pathogenesis. PMID:24006841

Heterologous expression of glycopeptide resistance vanHAX gene clusters from soil bacteria in Enterococcus faecalis.

PubMed

Hasman, Henrik; Aarestrup, Frank M; Dalsgaard, Anders; Guardabassi, Luca

2006-04-01

The aim of the study was to determine whether glycopeptide resistance gene clusters from soil bacteria could be heterologously expressed in Enterococcus faecalis and adapt to the new host following exposure to vancomycin. The vanHAX clusters from Paenibacillus thiaminolyticus PT-2B1, Paenibacillus apiarius PA-B2B and Amycolatopsis coloradensis DSM 44225 were separately cloned in an appropriately constructed shuttle vector containing the two-component regulatory system (vanRS) of Tn1546. The complete vanA(PT) operon (vanRSHAXY) from P. thiaminolyticus PT-2B1 was cloned in the same shuttle vector lacking enterococcal vanRS. All plasmid constructs were electroporated into E. faecalis JH2-2 and the MICs of vancomycin and teicoplanin were determined for each recombinant strain before and following exposure to sublethal concentrations of vancomycin. The vanHAX clusters from P. thiaminolyticus and P. apiarius conferred high-level vancomycin resistance (MIC > or = 125 mg/L) in E. faecalis JH2-2. In contrast, cloning of the vanHAX cluster from A. coloradensis did not result in a significant increase of vancomycin resistance (MIC = 0.7 mg/L). Resistance to vancomycin was not observed after cloning the complete vanA(PT) operon from P. thiaminolyticus (MIC = 2 mg/L), but this recombinant rapidly adapted to high concentrations of vancomycin (MIC = 500 mg/L) following exposure to sub-lethal concentrations of this antibiotic. The results showed that vanA(PT) in P. thiaminolyticus is a possible ancestor of vanA-mediated glycopeptide resistance in enterococci. Experimental evidence supported the hypothesis that enterococci did not acquire glycopeptide resistance directly from glycopeptide-producing organisms such as A. coloradensis.

Adamantoylated biologically active small peptides and glycopeptides structurally related to the bacterial peptidoglycan.

PubMed

Frkanec, Ruža; Vranešić, Branka; Tomić, Srdjanka

2013-01-01

A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity, particularly immunomodulating properties. A series of compounds containing the adamantyl residues coupled to peptides and glycopeptides characteristic for bacterial peptidoglycan was described. The new adamantylpeptides and adamantylglycopeptides were prepared starting from N-protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the starting material was D,L-(adamantyl-glycine) the condensation products with the dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were separated, characterized, and tested for immunostimulating activity. An HPLC method for purity testing was developed and adapted for the particular compounds.

Cysteine S-glycosylation, a new post-translational modification found in glycopeptide bacteriocins.

PubMed

Stepper, Judith; Shastri, Shilpa; Loo, Trevor S; Preston, Joanne C; Novak, Petr; Man, Petr; Moore, Christopher H; Havlíček, Vladimír; Patchett, Mark L; Norris, Gillian E

2011-02-18

O-Glycosylation is a ubiquitous eukaryotic post-translational modification, whereas early reports of S-linked glycopeptides have never been verified. Prokaryotes also glycosylate proteins, but there are no confirmed examples of sidechain glycosylation in ribosomal antimicrobial polypeptides collectively known as bacteriocins. Here we show that glycocin F, a bacteriocin secreted by Lactobacillus plantarum KW30, is modified by an N-acetylglucosamine β-O-linked to Ser18, and an N-acetylhexosamine S-linked to C-terminal Cys43. The O-linked N-acetylglucosamine is essential for bacteriostatic activity, and the C-terminus is required for full potency (IC(50) 2 nM). Genomic context analysis identified diverse putative glycopeptide bacteriocins in Firmicutes. One of these, the reputed lantibiotic sublancin, was shown to contain a hexose S-linked to Cys22. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

NASA Astrophysics Data System (ADS)

Roy, Rini; Ang, Evelyn; Komatsu, Emy; Domalaon, Ronald; Bosseboeuf, Adrien; Harb, Jean; Hermouet, Sylvie; Krokhin, Oleg; Schweizer, Frank; Perreault, Hélène

2018-05-01

Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

Design and synthesis of multifunctional gold nanoparticles bearing tumor-associated glycopeptide antigens as potential cancer vaccines.

PubMed

Brinãs, Raymond P; Sundgren, Andreas; Sahoo, Padmini; Morey, Susan; Rittenhouse-Olson, Kate; Wilding, Greg E; Deng, Wei; Barchi, Joseph J

2012-08-15

The development of vaccines against specific types of cancers will offer new modalities for therapeutic intervention. Here, we describe the synthesis of a novel vaccine construction prepared from spherical gold nanoparticles of 3-5 nm core diameters. The particles were coated with both the tumor-associated glycopeptides antigens containing the cell-surface mucin MUC4 with Thomsen Friedenreich (TF) antigen attached at different sites and a 28-residue peptide from the complement derived protein C3d to act as a B-cell activating "molecular adjuvant". The synthesis entailed solid-phase glycopeptide synthesis, design of appropriate linkers, and attachment chemistry of the various molecules to the particles. Attachment to the gold surface was mediated by a novel thiol-containing 33 atom linker which was further modified to be included as a third "spacer" component in the synthesis of several three-component vaccine platforms. Groups of mice were vaccinated either with one of the nanoplatform constructs or with control particles without antigen coating. Evaluation of sera from the immunized animals in enzyme immunoassays (EIA) against each glycopeptide antigen showed a small but statistically significant immune response with production of both IgM and IgG isotypes. Vaccines with one carbohydrate antigen (B, C, and E) gave more robust responses than the one with two contiguous disaccharides (D), and vaccine E with a TF antigen attached to threonine at the 10th position of the peptide was selected for IgG over IgM suggesting isotype switching. The data suggested that this platform may be a viable delivery system for tumor-associated glycopeptide antigens.

Antigiardial activity of glycoproteins and glycopeptides from Ziziphus honey.

PubMed

Mohammed, Seif Eldin A; Kabashi, Ahmed S; Koko, Waleed S; Azim, M Kamran

2015-01-01

Natural honey contains an array of glycoproteins, proteoglycans and glycopeptides. Size-exclusion chromatography fractionated Ziziphus honey proteins into five peaks with molecular masses in the range from 10 to >200 kDa. The fractionated proteins exhibited in vitro activities against Giardia lamblia with IC50 values ≤ 25 μg/mL. Results indicated that honey proteins were more active as antiprotozoal agents than metronidazole. This study indicated the potential of honey proteins and peptides as novel antigiardial agents.

Members of the Genera Paenibacillus and Rhodococcus Harbor Genes Homologous to Enterococcal Glycopeptide Resistance Genes vanA and vanB

PubMed Central

Guardabassi, L.; Christensen, H.; Hasman, H.; Dalsgaard, A.

2004-01-01

Genes homologous to enterococcal glycopeptide resistance genes vanA and vanB were found in glycopeptide-resistant Paenibacillus and Rhodococcus strains from soil. The putative d-Ala:d-Lac ligase genes in Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B were closely related to vanA (92 and 87%) and flanked by genes homologous to vanH and vanX in vanA operons. PMID:15561881

Members of the genera Paenibacillus and Rhodococcus harbor genes homologous to enterococcal glycopeptide resistance genes vanA and vanB.

PubMed

Guardabassi, L; Christensen, H; Hasman, H; Dalsgaard, A

2004-12-01

Genes homologous to enterococcal glycopeptide resistance genes vanA and vanB were found in glycopeptide-resistant Paenibacillus and Rhodococcus strains from soil. The putative D-Ala:D-Lac ligase genes in Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B were closely related to vanA (92 and 87%) and flanked by genes homologous to vanH and vanX in vanA operons.

Analysis of Glycoproteins in Human Serum by Means of Glycospecific Magnetic Bead Separation and LC-MALDI-TOF/TOF Analysis with Automated Glycopeptide Detection

PubMed Central

Sparbier, Katrin; Asperger, Arndt; Resemann, Anja; Kessler, Irina; Koch, Sonja; Wenzel, Thomas; Stein, Günter; Vorwerg, Lars; Suckau, Detlev; Kostrzewa, Markus

2007-01-01

Comprehensive proteomic analyses require efficient and selective pre-fractionation to facilitate analysis of post-translationally modified peptides and proteins, and automated analysis workflows enabling the detection, identification, and structural characterization of the corresponding peptide modifications. Human serum contains a high number of glycoproteins, comprising several orders of magnitude in concentration. Thereby, isolation and subsequent identification of low-abundant glycoproteins from serum is a challenging task. selective capturing of glycopeptides and -proteins was attained by means of magnetic particles specifically functionalized with lectins or boronic acids that bind to various structural motifs. Human serum was incubated with differentially functionalized magnetic micro-particles (lectins or boronic acids), and isolated proteins were digested with trypsin. Subsequently, the resulting complex mixture of peptides and glycopeptides was subjected to LC-MALDI analysis and database searching. In parallel, a second magnetic bead capturing was performed on the peptide level to separate and analyze by LC-MALDI intact glycopeptides, both peptide sequence and glycan structure. Detection of glycopeptides was achieved by means of a software algorithm that allows extraction and characterization of potential glycopeptide candidates from large LC-MALDI-MS/MS data sets, based on N-glycopeptide-specific fragmentation patterns and characteristic fragment mass peaks, respectively. By means of fast and simple glycospecific capturing applied in conjunction with extensive LC-MALDI-MS/MS analysis and novel data analysis tools, a high number of low-abundant proteins were identified, comprising known or predicted glycosylation sites. According to the specific binding preferences of the different types of beads, complementary results were obtained from the experiments using either magnetic ConA-, LCA-, WGA-, and boronic acid beads, respectively. PMID:17916798

Click Synthesis of Hydrophilic Maltose-Functionalized Iron Oxide Magnetic Nanoparticles Based on Dopamine Anchors for Highly Selective Enrichment of Glycopeptides.

PubMed

Bi, Changfen; Zhao, Yingran; Shen, Lijin; Zhang, Kai; He, Xiwen; Chen, Langxing; Zhang, Yukui

2015-11-11

The development of methods to isolate and enrich low-abundance glycopeptides from biological samples is crucial to glycoproteomics. Herein, we present an easy and one-step surface modification strategy to prepare hydrophilic maltose functionalized Fe3O4 nanoparticles (NPs). First, based on the chelation of the catechol ligand with iron atoms, azido-terminated dopamine (DA) derivative was assembled on the surface of magnetic Fe3O4 nanoparticles by sonication. Second, the hydrophilic maltose-functionalized Fe3O4 (Fe3O4-DA-Maltose) NPs were obtained via copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry). The morphology, structure, and composition of Fe3O4-DA-Maltose NPs were investigated by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), X-ray photoelectron spectrometer (XPS), and vibrating sample magnetometer (VSM). Meanwhile, hydrophilicity of the obtained NPs was evaluated by water contact angle measurement. The hydrophilic Fe3O4-DA-Maltose NPs were applied in isolation and enrichment of glycopeptides from horseradish peroxidase (HRP), immunoglobulin (IgG) digests. The MALDI-TOF mass spectrometric analysis indicated that the novel NPs exhibited high detection sensitivity in enrichment from HRP digests at concentration as low as 0.05 ng μL(-1), a large binding capacity up to 43 mg g(-1), and good recovery for glycopeptides enrichment (85-110%). Moreover, the Fe3O4-DA-Maltose NPs were applied to enrich glycopeptides from human renal mesangial cells (HRMC) for identification of N-glycosylation sites. Finally, we identified 115 different N-linked glycopeptides, representing 93 gene products and 124 glycosylation sites in HRMC.

Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins

PubMed Central

Li, Yingxue; Lefever, Mark R; Muthu, Dhanasekaran; Bidlack, Jean M; Bilsky, Edward J; Polt, Robin

2012-01-01

Over the past two decades, potent and selective analgesics have been developed from endogenous opioid peptides. Glycosylation provides an important means of modulating interaction with biological membranes, which greatly affects the pharmacodynamics and pharmacokinetics of the resulting glycopeptide analogues. Furthermore, manipulation of the membrane affinity allows penetration of cellular barriers that block efficient drug distribution, including the blood–brain barrier. Extremely potent and selective opiate agonists have been developed from endogenous peptides, some of which show great promise as drug candidates. PMID:22300099

An engineered high affinity Fbs1 carbohydrate binding protein for selective capture of N-glycans and N-glycopeptides

PubMed Central

Chen, Minyong; Shi, Xiaofeng; Duke, Rebecca M.; Ruse, Cristian I.; Dai, Nan; Taron, Christopher H.; Samuelson, James C.

2017-01-01

A method for selective and comprehensive enrichment of N-linked glycopeptides was developed to facilitate detection of micro-heterogeneity of N-glycosylation. The method takes advantage of the inherent properties of Fbs1, which functions within the ubiquitin-mediated degradation system to recognize the common core pentasaccharide motif (Man3GlcNAc2) of N-linked glycoproteins. We show that Fbs1 is able to bind diverse types of N-linked glycomolecules; however, wild-type Fbs1 preferentially binds high-mannose-containing glycans. We identified Fbs1 variants through mutagenesis and plasmid display selection, which possess higher affinity and improved recovery of complex N-glycomolecules. In particular, we demonstrate that the Fbs1 GYR variant may be employed for substantially unbiased enrichment of N-linked glycopeptides from human serum. Most importantly, this highly efficient N-glycopeptide enrichment method enables the simultaneous determination of N-glycan composition and N-glycosites with a deeper coverage (compared to lectin enrichment) and improves large-scale N-glycoproteomics studies due to greatly reduced sample complexity. PMID:28534482

Hexapeptide Derivatives of Glycopeptide Antibiotics: Tools for Mechanism of Action Studies

PubMed Central

Allen, Norris E.; LeTourneau, Deborah L.; Hobbs, Joe N.; Thompson, Richard C.

2002-01-01

Hexapeptide (des-N-methylleucyl) derivatives of LY264826 were prepared in order to examine further the role of N-substituted hydrophobic side chains in defining the mechanisms of action of semisynthetic glycopeptide antibiotics. The hexapeptide of LY264826 binds to the cell wall intermediate analog l-Lys-d-Ala-d-Ala with a 100-fold lower affinity than LY264826 and inhibits Micrococcus luteus almost 200-fold more poorly than LY264826 does. Alkylation of the 4-epi-vancosamine moiety of the disaccharide significantly enhanced the antibacterial activity of the hexapeptide. Alkylation did not affect the binding affinity for d-alanyl-d-alanine residues; however, it did enhance dimerization 7,000-fold and enhanced binding to bacterial membrane vesicles noticeably compared with the levels of dimerization and binding for the unsubstituted hexapeptide. The findings from this study complement those presented in an earlier report (N. E. Allen, D. L. LeTourneau, and J. N. Hobbs, Jr., J. Antibiot. 50:677-684, 1997) and are consistent with the conclusion that the enhanced antibacterial activities of semisynthetic glycopeptide antibiotics derive from the ability of the hydrophobic side chain to markedly affect both dimerization and binding to bacterial membranes. PMID:12121903

A fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic.

PubMed

Chen, Kuncai; He, Rong; Luo, Xiaoyan; Qin, Pengzhe; Tan, Lei; Tang, Youwen; Yang, Zhicong

2017-08-15

This paper demonstrates a new strategy for developing a fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic. The technique provides amino modified Mn-doped ZnS QDs as fluorescent supports, 4-vinylphenylbronic acid as a covalent monomer, N-isopropyl acrylamide as a thermo-responsive monomer in combination with acrylamide as a non-covalent monomer, and glycosyl moiety of a glycopeptide antibiotic as a template to produce fluorescent molecularly imprinted polymer (FMIP) in aqueous solution. The FMIP can alter its functional moieties and structure with pH and temperature stimulation. This allows recognition of target molecules through control of pH and temperature. The fluorescence intensity of the FMIP was enhanced gradually as the concentration of telavancin increased, and showed selective recognition toward the target glycopeptide antibiotic preferentially among other antibiotics. Using the FMIP as a sensing material, good linear correlations were obtained over the concentration range of 3.0-300.0μg/L and with a low limit of detection of 1.0μg/L. The analysis results of telavancin in real samples were consistent with that obtained by liquid chromatography tandem mass spectrometry. Copyright © 2017 Elsevier B.V. All rights reserved.

Heterogeneous resistance to vancomycin in Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains: characterisation of glycopeptide susceptibility profiles and cell wall thickening.

PubMed

Nunes, Ana Paula Ferreira; Teixeira, Lúcia Martins; Iorio, Natália Lopes Pontes; Bastos, Carla Callegário Reis; de Sousa Fonseca, Leila; Souto-Padrón, Thaís; dos Santos, Kátia Regina Netto

2006-04-01

The population analysis profile (PAP) method as well as analysis of autolytic activity and cellular ultrastructure by transmission electron microscopy (TEM) were used to characterise Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains with reduced susceptibility to glycopeptides. All strains showed heterogeneous profiles to vancomycin and teicoplanin by the PAP method. Subpopulations that grew in the presence of high concentrations of each drug were selected from the PAP as derivative strains. Their glycopeptide minimal inhibitory concentrations (MICs) were determined and subsequently all parental and derivative strains were grown in one-half of the MIC of vancomycin or teicoplanin. An increase in cell wall thickness of all derivative strains was seen by TEM, with statistically significant values (P<0.01) compared with their respective parental strains. In general, variable rates of autolysis among the strains were observed. Cell wall thickness is an important factor involved in glycopeptide resistance and, in association with PAP results, confirmed the Brazilian coagulase-negative staphylococci clinical isolates as being heteroresistant to glycopeptides. Detection of these heteroresistant organisms is important in order to achieve more judicious use of vancomycin and teicoplanin in hospitals.

Increasing the productivity of glycopeptides analysis by using higher-energy collision dissociation-accurate mass-product-dependent electron transfer dissociation.

PubMed

Saba, Julian; Dutta, Sucharita; Hemenway, Eric; Viner, Rosa

2012-01-01

Currently, glycans are attracting attention from the scientific community as potential biomarkers or as posttranslational modifications (PTMs) of therapeutic proteins. However, structural characterization of glycoproteins and glycopeptides remains analytically challenging. Here, we report on the implementation of a novel acquisition strategy termed higher-energy collision dissociation-accurate mass-product-dependent electron transfer dissociation (HCD-PD-ETD) on a hybrid linear ion trap-orbitrap mass spectrometer. This acquisition strategy uses the complementary fragmentations of ETD and HCD for glycopeptides analysis in an intelligent fashion. Furthermore, the approach minimizes user input for optimizing instrumental parameters and enables straightforward detection of glycopeptides. ETD spectra are only acquired when glycan oxonium ions from MS/MS HCD are detected. The advantage of this approach is that it streamlines data analysis and improves dynamic range and duty cycle. Here, we present the benefits of HCD-PD-ETD relative to the traditional alternating HCD/ETD for a trainer set containing twelve-protein mixture with two glycoproteins: human serotransferrin, ovalbumin and contaminations of two other: bovine alpha 1 acid glycoprotein (bAGP) and bovine fetuin.

Synthesis of hydrazide-functionalized hydrophilic polymer hybrid graphene oxide for highly efficient N-glycopeptide enrichment and identification by mass spectrometry.

PubMed

Bai, Haihong; Pan, Yiting; Guo, Cong; Zhao, Xinyuan; Shen, Bingquan; Wang, Xinghe; Liu, Zeyuan; Cheng, Yuanguo; Qin, Weijie; Qian, Xiaohong

2017-08-15

Protein N-glycosylation is one of the most important post-translational modifications, participating in many key biological and pathological processes. Large-scale and precise identification of N-glycosylated proteins and peptides is especially beneficial for understanding their biological functions and for discovery of new clinical biomarkers and therapeutic drug targets. However, protein N-glycosylation is microheterogeneous and low abundant in living organisms, therefore specific enrichment of N-glycosylated proteins/peptides before mass spectrometry analysis is a prerequisite. In this work, we developed a new type of polymer hybrid graphene oxide (GO) by in situ growth of hydrazide-functionalized hydrophilic polymer chains on the GO surface (GO-PAAH) for selective N-glycopeptide enrichment and identification by mass spectrometry. The densely attached and low steric hindrance hydrazide groups as well as the highly hydrophilic nature of GO-PAAH facilitate N-glycopeptide enrichment by the combination of hydrazide capturing and HILIC interaction. Taking advantage of the unique features of GO-PAAH, all of the three N-glycopeptides of bovine fetuin were successfully enriched and identified with significantly enhanced signal intensities from a digest mixture of bovine fetuin and bovine serum albumin at a mass ratio of 1:100, demonstrating the excellent enrichment selectivity of GO-PAAH. Furthermore, a total of 507 N-glycosylation sites and 480 N-glycopeptides in 232 N-glycoproteins were enriched and identified from 10μL of human serum by three replicates using this novel enrichment material, which is nearly two times higher than the commercial hydrazide resin based method (280 N-glycosylation sites, 261 N-glycopeptides and 144 N-glycoproteins in three experiments). Among the identified, 95 N-glycosylation sites were not reported in the Uniprot database, and 106 N-glycoproteins were disease related in the Nextprot database, indicating the potential of this new

Ultra-high performance liquid chromatography tandem mass spectrometry for the determination of five glycopeptide antibiotics in food and biological samples using solid-phase extraction.

PubMed

Deng, Fenfang; Yu, Hong; Pan, Xinhong; Hu, Guoyuan; Wang, Qiqin; Peng, Rongfei; Tan, Lei; Yang, Zhicong

2018-02-23

This paper demonstrated the development and validation of an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of five glycopeptide antibiotics in food and biological samples. The target glycopeptide antibiotics were isolated from the samples by solvent extraction, and the extracts were cleaned with a tandem solid-phase extraction step using mixed strong cation exchange and hydrophilic/lipophilic balance cartridges. Subsequently, the analytes were eluted with different solvents, and then quantified by UHPLC-MS/MS in the positive ionization mode with multiple reaction monitoring. Under optimal conditions, good linear correlations were obtained for the five glycopeptide antibiotics in the concentration range of 1.0 μg/L to 20.0 μg/L, and with linear correlation coefficients >0.998. Employing this method, the target glycopeptide antibiotics in food and biological samples were identified with a recovery of 83.0-102%, and a low quantitation limit of 1.0 μg/kg in food and 2.0 μg/L in biological samples with low matrix effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Facile and easily popularized synthesis of L-cysteine-functionalized magnetic nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides.

PubMed

Feng, Xiaoyan; Deng, Chunhui; Gao, Mingxia; Zhang, Xiangmin

2018-01-01

Protein glycosylation is one of the most important post-translational modifications. Also, efficient enrichment and separation of glycopeptides from complex samples are crucial for the thorough analysis of glycosylation. Developing novel hydrophilic materials with facile and easily popularized synthesis is an urgent need in large-scale glycoproteomics research. Herein, for the first time, a one-step functionalization strategy based on metal-organic coordination was proposed and Fe 3 O 4 nanoparticles were directly functionalized with zwitterionic hydrophilic L-cysteine (L-Cys), greatly simplifying the synthetic procedure. The easily synthesized Fe 3 O 4 /L-Cys possessed excellent hydrophilicity and brief composition, contributing to affinity for glycopeptides and reduction in nonspecific interaction. Thus, Fe 3 O 4 /L-Cys nanoparticles showed outstanding sensitivity (25 amol/μL), high selectivity (mixture of bovine serum albumin and horseradish peroxidase tryptic digests at a mass ratio of 100:1), good reusability (five repeated times), and stability (room temperature storage of 1 month). Encouragingly, in the glycosylation analysis of human serum, a total of 376 glycopeptides with 393 N-glycosylation sites corresponding to 118 glycoproteins were identified after enrichment with Fe 3 O 4 /L-Cys, which was superior to ever reported L-Cys modified magnetic materials. Furthermore, applying the one-step functionalization strategy, cysteamine and glutathione respectively direct-functionalized Fe 3 O 4 nanoparticles were successfully synthesized and also achieved efficient glycopeptide enrichment in human serum. The results indicated that we have presented an efficient and easily popularized strategy in glycoproteomics as well as in the synthesis of novel materials. Graphical abstract Fe 3 O 4 /L-Cys nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides.

3-Aminoquinoline/p-coumaric acid as a MALDI matrix for glycopeptides, carbohydrates, and phosphopeptides.

PubMed

Fukuyama, Yuko; Funakoshi, Natsumi; Takeyama, Kohei; Hioki, Yusaku; Nishikaze, Takashi; Kaneshiro, Kaoru; Kawabata, Shin-Ichirou; Iwamoto, Shinichi; Tanaka, Koichi

2014-02-18

Glycosylation and phosphorylation are important post-translational modifications in biological processes and biomarker research. The difficulty in analyzing these modifications is mainly their low abundance and dissociation of labile regions such as sialic acids or phosphate groups. One solution in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is to improve matrices for glycopeptides, carbohydrates, and phosphopeptides by increasing the sensitivity and suppressing dissociation of the labile regions. Recently, a liquid matrix 3-aminoquinoline (3-AQ)/α-cyano-4-hydroxycinnamic acid (CHCA) (3-AQ/CHCA), introduced by Kolli et al. in 1996, has been reported to increase sensitivity for carbohydrates or phosphopeptides, but it has not been systematically evaluated for glycopeptides. In addition, 3-AQ/CHCA enhances the dissociation of labile regions. In contrast, a liquid matrix 1,1,3,3-tetramethylguanidium (TMG, G) salt of p-coumaric acid (CA) (G3CA) was reported to suppress dissociation of sulfate groups or sialic acids of carbohydrates. Here we introduce a liquid matrix 3-AQ/CA for glycopeptides, carbohydrates, and phosphopeptides. All of the analytes were detected as [M + H](+) or [M - H](-) with higher or comparable sensitivity using 3-AQ/CA compared with 3-AQ/CHCA or 2,5-dihydroxybenzoic acid (2,5-DHB). The sensitivity was increased 1- to 1000-fold using 3-AQ/CA. The dissociation of labile regions such as sialic acids or phosphate groups and the fragmentation of neutral carbohydrates were suppressed more using 3-AQ/CA than using 3-AQ/CHCA or 2,5-DHB. 3-AQ/CA was thus determined to be an effective MALDI matrix for high sensitivity and the suppression of dissociation of labile regions in glycosylation and phosphorylation analyses.

Linkage-specific sialic acid derivatization for MALDI-TOF-MS profiling of IgG glycopeptides.

PubMed

de Haan, Noortje; Reiding, Karli R; Haberger, Markus; Reusch, Dietmar; Falck, David; Wuhrer, Manfred

2015-08-18

Glycosylation is a common co- and post-translational protein modification, having a large influence on protein properties like conformation and solubility. Furthermore, glycosylation is an important determinant of efficacy and clearance of biopharmaceuticals such as immunoglobulin G (IgG). Matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS) shows potential for the site-specific glycosylation analysis of IgG at the glycopeptide level. With this approach, however, important information about glycopeptide sialylation is not duly covered because of in-source and metastable decay of the sialylated species. Here, we present a highly repeatable sialic acid derivatization method to allow subclass-specific MALDI-TOF-MS analysis of tryptic IgG glycopeptides. The method, employing dimethylamidation with the carboxylic acid activator 1-ethyl-3-(3-dimethylamino)propyl)carbodiimide (EDC) and the catalyst 1-hydroxybenzotriazole (HOBt), results in different masses for the functionally divergent α2,3- and α2,6-linked sialic acids. Respective lactonization and dimethylamidation leads to their direct discrimination in MS and importantly, both glycan and peptide moieties reacted in a controlled manner. In addition, stabilization allowed the acquisition of fragmentation spectra informative with respect to glycosylation and peptide sequence. This was in contrast to fragmentation spectra of underivatized samples, which were dominated by sialic acid loss. The method allowed the facile discrimination and relative quantitation of IgG Fc sialylation in therapeutic IgG samples. The method has considerable potential for future site- and sialic acid linkage-specific glycosylation profiling of therapeutic antibodies, as well as for subclass-specific biomarker discovery in clinical IgG samples derived from plasma.

[Antipsychotic-induced weight gain--pharmacogenetic studies].

PubMed

Olajossy-Hilkesberger, Luiza; Godlewska, Beata; Marmurowska-Michałowskal, Halina; Olajossy, Marcin; Landowski, Jerzy

2006-01-01

Drug-naive patients with schizophrenia often present metabolic abnormalities and obesity. Weight gain may be the side effect of treatment with many antipsychotic drugs. Genetic effects, besides many other factors, are known to influence obesity in patients with schizophrenia treated with antipsychotics. Numerous studies of several genes' polymorphisms have been performed. -759C/T polymorphism of 5HT2C gene attracted most attention. In 5 independent studies of this polymorphism the association between T allele with the lower AP-induced weight gain was detected. No associations could be detected between weight gain and other polymorphisms of serotonergic system genes as well as histaminergic system genes. Studies of adrenergic and dopaminergic system have neither produced any unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene) confirmed the role of genetic factors in AP-induced weight gain. It is worth emphasising, that the studies have been conducted in relatively small and heterogenic groups and that various treatment strategies were used.

Genetically Encoded Fragment-Based Discovery of Glycopeptide Ligands for Carbohydrate-Binding Proteins

DOE PAGES

Ng, Simon; Lin, Edith; Kitov, Pavel I.; ...

2015-04-10

Here we describe an approach to accelerate the search for competitive inhibitors for carbohydrate-recognition domains (CRDs). Genetically encoded fragment-based-discovery (GE-FBD) uses selection of phagedisplayed glycopeptides to dock a glycan fragment at the CRD and guide selection of Synergistic peptide motifs adjacent to the CRD. Starting from concanavalin A (ConA), a mannose (Man)-binding protein, as a bait, we narrowed a library of 10 8 glycopeptides to 86 leads that share a consensus motif, Man-WYD. Validation of synthetic leads yielded Man-WYDLF that exhibited 40 50-fold enhancement in affinity over methyl α-D-mannopyranoside (MeMan). Lectin array Suggested specificity: Man-WYD derivative bound only to 3more » out of 17 proteins-ConA, LcH, and PSA-that bind to Man. An X-ray structure of ConA.:Man-WYD proved that the trimannoside core and Man-WYD exhibit identical CRD docking; but their extra-CRD binding modes are significantly. different. Still, they have comparable affinity and selectivity for various Man-binding proteins. The intriguing observation provides new insight into functional mimicry :of carbohydrates by peptide ligands. GE-FBD may provide an alternative to rapidly search for competitive inhibitors for lectins.« less

Genetically Encoded Fragment-Based Discovery of Glycopeptide Ligands for Carbohydrate-Binding Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Simon; Lin, Edith; Kitov, Pavel I.

Here we describe an approach to accelerate the search for competitive inhibitors for carbohydrate-recognition domains (CRDs). Genetically encoded fragment-based-discovery (GE-FBD) uses selection of phagedisplayed glycopeptides to dock a glycan fragment at the CRD and guide selection of Synergistic peptide motifs adjacent to the CRD. Starting from concanavalin A (ConA), a mannose (Man)-binding protein, as a bait, we narrowed a library of 10 8 glycopeptides to 86 leads that share a consensus motif, Man-WYD. Validation of synthetic leads yielded Man-WYDLF that exhibited 40 50-fold enhancement in affinity over methyl α-D-mannopyranoside (MeMan). Lectin array Suggested specificity: Man-WYD derivative bound only to 3more » out of 17 proteins-ConA, LcH, and PSA-that bind to Man. An X-ray structure of ConA.:Man-WYD proved that the trimannoside core and Man-WYD exhibit identical CRD docking; but their extra-CRD binding modes are significantly. different. Still, they have comparable affinity and selectivity for various Man-binding proteins. The intriguing observation provides new insight into functional mimicry :of carbohydrates by peptide ligands. GE-FBD may provide an alternative to rapidly search for competitive inhibitors for lectins.« less

Antipsychotic induced weight gain in schizophrenia:mechanisms and management.

PubMed

Rege, Sanil

2008-05-01

The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible

Parallel Comparison of N-Linked Glycopeptide Enrichment Techniques Reveals Extensive Glycoproteomic Analysis of Plasma Enabled by SAX-ERLIC.

PubMed

Totten, Sarah M; Feasley, Christa L; Bermudez, Abel; Pitteri, Sharon J

2017-03-03

Protein glycosylation is of increasing interest due to its important roles in protein function and aberrant expression with disease. Characterizing protein glycosylation remains analytically challenging due to its low abundance, ion suppression issues, and microheterogeneity at glycosylation sites, especially in complex samples such as human plasma. In this study, the utility of three common N-linked glycopeptide enrichment techniques is compared using human plasma. By analysis on an LTQ-Orbitrap Elite mass spectrometer, electrostatic repulsion hydrophilic interaction liquid chromatography using strong anion exchange solid-phase extraction (SAX-ERLIC) provided the most extensive N-linked glycopeptide enrichment when compared with multilectin affinity chromatography (M-LAC) and Sepharose-HILIC enrichments. SAX-ERLIC enrichment yielded 191 unique glycoforms across 72 glycosylation sites from 48 glycoproteins, which is more than double that detected using other enrichment techniques. The greatest glycoform diversity was observed in SAX-ERLIC enrichment, with no apparent bias toward specific glycan types. SAX-ERLIC enrichments were additionally analyzed by an Orbitrap Fusion Lumos mass spectrometer to maximize glycopeptide identifications for a more comprehensive assessment of protein glycosylation. In these experiments, 829 unique glycoforms were identified across 208 glycosylation sites from 95 plasma glycoproteins, a significant improvement from the initial method comparison and one of the most extensive site-specific glycosylation analysis in immunodepleted human plasma to date. Data are available via ProteomeXchange with identifier PXD005655.

Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring.

PubMed

Darebna, Petra; Novak, Petr; Kucera, Radek; Topolcan, Ondrej; Sanda, Miloslav; Goldman, Radoslav; Pompach, Petr

2017-02-05

Alternations in the glycosylation of proteins have been described in connection with several cancers, including hepatocellular carcinoma (HCC) and colorectal cancer. Analytical tools, which use combination of liquid chromatography and mass spectrometry, allow precise and sensitive description of these changes. In this study, we use MRM and FT-ICR operating in full-MS scan, to determine ratios of intensities of specific glycopeptides in HCC, colorectal cancer, and liver metastasis of colorectal cancer. Haptoglobin, hemopexin and complement factor H were detected after albumin depletion and the N-linked glycopeptides with fucosylated glycans were compared with their non-fucosylated forms. In addition, sialylated forms of an O-linked glycopeptide of hemopexin were quantified in the same samples. We observe significant increase in fucosylation of all three proteins and increase in bi-sialylated O-glycopeptide of hemopexin in HCC of hepatitis C viral (HCV) etiology by both LC-MS methods. The results of the MRM and full-MS scan FT-ICR analyses provide comparable quantitative readouts in spite of chromatographic, mass spectrometric and data analysis differences. Our results suggest that both workflows allow adequate relative quantification of glycopeptides and suggest that HCC of HCV etiology differs in glycosylation from colorectal cancer and liver metastasis of colorectal cancer. The article compares N- and O-glycosylation of several serum proteins in different diseases by a fast and easy sample preparation procedure in combination with high resolution Fourier transform ion cyclotron resonance mass spectrometry. The results show successful glycopeptides relative quantification in a complex peptide mixture by the high resolution instrument and the detection of glycan differences between the different types of cancer diseases. The presented method is comparable to conventional targeted MRM approach but allows additional curation of the data. Copyright © 2016 Elsevier B

Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring

PubMed Central

Darebna, Petra; Novak, Petr; Kucera, Radek; Topolcan, Ondrej; Sanda, Miloslav; Goldman, Radoslav; Pompach, Petr

2018-01-01

Alternations in the glycosylation of proteins have been described in connection with several cancers, including hepatocellular carcinoma (HCC) and colorectal cancer. Analytical tools, which use combination of liquid chromatography and mass spectrometry, allow precise and sensitive description of these changes. In this study, we use MRM and FT-ICR operating in full-MS scan, to determine ratios of intensities of specific glycopeptides in HCC, colorectal cancer, and liver metastasis of colorectal cancer. Haptoglobin, hemopexin and complement factor H were detected after albumin depletion and the N-linked glycopeptides with fucosylated glycans were compared with their non-fucosylated forms. In addition, sialylated forms of an O-linked glycopeptide of hemopexin were quantified in the same samples. We observe significant increase in fucosylation of all three proteins and increase in bisialylated O-glycopeptide of hemopexin in HCC of hepatitis C viral (HCV) etiology by both LC-MS methods. The results of the MRM and full-MS scan FT-ICR analyses provide comparable quantitative readouts in spite of chromatographic, mass spectrometric and data analysis differences. Our results suggest that both workflows allow adequate relative quantification of glycopeptides and suggest that HCC of HCV etiology differs in glycosylation from colorectal cancer and liver metastasis of colorectal cancer. Significance The article compares N- and O-glycosylation of several serum proteins in different diseases by a fast and easy sample preparation procedure in combination with high resolution Fourier transform ion cyclotron resonance mass spectrometry. The results show successful glycopeptides relative quantification in a complex peptide mixture by the high resolution instrument and the detection of glycan differences between the different types of cancer diseases. The presented method is comparable to conventional targeted MRM approach but allows additional curation of the data. PMID:27646713

Characterization of a novel antibacterial glycopeptide produced by Penicillium sp. M03.

PubMed

Yang, W H; Zhang, W C; Lu, X M; Jiang, G S; Gao, P J

2009-04-01

To isolate a novel antibiotic termed AF from fermentation broth of Penicillium sp. M03 and to examine its antimicrobial activity, biological properties and structure characteristics. Sephadex LH-20 and HPLC were used to purify AF from fermentation broth of Penicillium sp. M03. The antimicrobial activity of AF was evaluated with the agar diffusion test. Amino acid and monosaccharide composition of AF was analysed by a HITACHI 835 detector and HPLC assay, respectively. Matrix-assisted laser desorption time of flight mass spectrometry, FT-IR and (1)H nuclear magnetic resonance spectra analyses were performed to examine the initial structure of AF. Eighty milligrams of AF was isolated as white powder from 1-l Penicillium sp. M03 fermentation broth. It consists of five amino acid and two monosaccharide residues and the molecular weight of it was 1017, and it was stable to beta-lactamase, heat, acid and alkali. AF showed inhibitory activity to a wide range of bacteria, particularly to multidrug-resistant Staphylococcus aureus. AF was a novel antibacterial glycopeptide with a broad inhibitory spectrum to pathogenic bacteria including multidrug-resistant agents. Furthermore, it is difficult to generate bacteria resistant to AF. Characterization of AF made it a potential antibiotic to fight against antibiotic-resistant bacterial pathogens.

High-yield secretion of recombinant proteins expressed in tobacco cell culture with a designer glycopeptide tag: Process development.

PubMed

Zhang, Ningning; Gonzalez, Maria; Savary, Brett; Xu, Jianfeng

2016-03-01

Low-yield protein production remains the most significant economic hurdle with plant cell culture technology. Fusions of recombinant proteins with hydroxyproline-O-glycosylated designer glycopeptide tags have consistently boosted secreted protein yields. This prompted us to study the process development of this technology aiming to achieve productivity levels necessary for commercial viability. We used a tobacco BY-2 cell culture expressing EGFP as fusion with a glycopeptide tag comprised of 32 repeat of "Ser-Pro" dipeptide, or (SP)32 , to study cell growth and protein secretion, culture scale-up, and establishment of perfusion cultures for continuous production. The BY-2 cells accumulated low levels of cell biomass (~7.5 g DW/L) in Schenk & Hildebrandt medium, but secreted high yields of (SP)32 -tagged EGFP (125 mg/L). Protein productivity of the cell culture has been stable for 6.0 years. The BY-2 cells cultured in a 5-L bioreactor similarly produced high secreted protein yield at 131 mg/L. Successful operation of a cell perfusion culture for 30 days was achieved under the perfusion rate of 0.25 and 0.5 day(-1) , generating a protein volumetric productivity of 17.6 and 28.9 mg/day/L, respectively. This research demonstrates the great potential of the designer glycopeptide technology for use in commercial production of valuable proteins with plant cell cultures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sulfated glycopeptide nanostructures for multipotent protein activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptidemore » nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.« less

Resistance to exercise-induced weight loss: compensatory behavioral adaptations.

PubMed

Melanson, Edward L; Keadle, Sarah Kozey; Donnelly, Joseph E; Braun, Barry; King, Neil A

2013-08-01

In many interventions that are based on an exercise program intended to induce weight loss, the mean weight loss observed is modest and sometimes far less than what the individual expected. The individual responses are also widely variable, with some individuals losing a substantial amount of weight, others maintaining weight, and a few actually gaining weight. The media have focused on the subpopulation that loses little weight, contributing to a public perception that exercise has limited utility to cause weight loss. The purpose of the symposium was to present recent, novel data that help explain how compensatory behaviors contribute to a wide discrepancy in exercise-induced weight loss. The presentations provide evidence that some individuals adopt compensatory behaviors, that is, increased energy intake and/or reduced activity, that offset the exercise energy expenditure and limit weight loss. The challenge for both scientists and clinicians is to develop effective tools to identify which individuals are susceptible to such behaviors and to develop strategies to minimize their effect.

Resistance to exercise-induced weight loss: compensatory behavioral adaptations

PubMed Central

Melanson, Edward L.; Keadle, Sarah Kozey; Donnelly, Joseph E.; Braun, Barry; King, Neil A.

2013-01-01

In many interventions that are based on an exercise program intended to induce weight loss, the mean weight loss observed is modest and sometimes far less than the individual expected. The individual responses are also widely variable, with some individuals losing a substantial amount of weight, others maintaining weight, and a few actually gaining weight. The media have focused on the sub-population that loses little weight, contributing to a public perception that exercise has limited utility to cause weight loss. The purpose of the symposium was to present recent, novel data that help explain how compensatory behaviors contribute to a wide discrepancy in exercise-induced weight loss. The presentations provide evidence that some individuals adopt compensatory behaviors, i.e. increased energy intake and/or reduced activity, that offset the exercise energy expenditure and limit weight loss. The challenge for both scientists and clinicians is to develop effective tools to identify which individuals are susceptible to such behaviors, and to develop strategies to minimize their impact. PMID:23470300

Acute liver injury induced by weight-loss herbal supplements.

PubMed

Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

2010-11-27

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.

Acute liver injury induced by weight-loss herbal supplements

PubMed Central

Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

2010-01-01

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss. PMID:21173910

Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing

NASA Astrophysics Data System (ADS)

Both, P.; Green, A. P.; Gray, C. J.; Šardzík, R.; Voglmeir, J.; Fontana, C.; Austeri, M.; Rejzek, M.; Richardson, D.; Field, R. A.; Widmalm, G.; Flitsch, S. L.; Eyers, C. E.

2014-01-01

Mass spectrometry is the primary analytical technique used to characterize the complex oligosaccharides that decorate cell surfaces. Monosaccharide building blocks are often simple epimers, which when combined produce diastereomeric glycoconjugates indistinguishable by mass spectrometry. Structure elucidation frequently relies on assumptions that biosynthetic pathways are highly conserved. Here, we show that biosynthetic enzymes can display unexpected promiscuity, with human glycosyltransferase pp-α-GanT2 able to utilize both uridine diphosphate N-acetylglucosamine and uridine diphosphate N-acetylgalactosamine, leading to the synthesis of epimeric glycopeptides in vitro. Ion-mobility mass spectrometry (IM-MS) was used to separate these structures and, significantly, enabled characterization of the attached glycan based on the drift times of the monosaccharide product ions generated following collision-induced dissociation. Finally, ion-mobility mass spectrometry following fragmentation was used to determine the nature of both the reducing and non-reducing glycans of a series of epimeric disaccharides and the branched pentasaccharide Man3 glycan, demonstrating that this technique may prove useful for the sequencing of complex oligosaccharides.

Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics.

PubMed

Miura, Yuri; Hashii, Noritaka; Ohta, Yuki; Itakura, Yoko; Tsumoto, Hiroki; Suzuki, Junya; Takakura, Daisuke; Abe, Yukiko; Arai, Yasumichi; Toyoda, Masashi; Kawasaki, Nana; Hirose, Nobuyoshi; Endo, Tamao

2018-06-01

Glycosylation is highly susceptible to changes of the physiological conditions, and accordingly, is a potential biomarker associated with several diseases and/or longevity. Semi-supercentenarians (SSCs; older than 105 years) are thought to be a model of human longevity. Thus, we performed glycoproteomics using plasma samples of SSCs, and identified proteins and conjugated N-glycans that are characteristic of extreme human longevity. Plasma proteins from Japanese semi-supercentenarians (SSCs, 106-109 years), aged controls (70-88 years), and young controls (20-38 years) were analysed by using lectin microarrays and liquid chromatography/mass spectrometry (LC/MS). Peak area ratios of glycopeptides to corresponding normalising peptides were subjected to orthogonal projections to latent structures discriminant analysis (OPLS-DA). Furthermore, plasma levels of clinical biomarkers were measured. We found two lectins such as Phaseolus vulgaris, and Erythrina cristagalli (ECA), of which protein binding were characteristically increased in SSCs. Peak area ratios of ECA-enriched glycopeptides were successfully discriminated between SSCs and controls using OPLS-DA, and indicated that tri-antennary and sialylated N-glycans of haptoglobin at Asn207 and Asn211 sites were characterized in SSCs. Sialylated glycans of haptoglobin are a potential biomarker of several diseases, such as hepatocellular carcinoma, liver cirrhosis, and IgA-nephritis. However, the SSCs analysed here did not suffer from these diseases. Tri-antennary and sialylated N-glycans on haptoglobin at the Asn207 and Asn211 sites were abundant in SSCs and characteristic of extreme human longevity. We found abundant glycans in SSCs, which may be associated with human longevity. Copyright © 2018 Elsevier B.V. All rights reserved.

Determination of asparagine, glutamine and pyrrolidonecarboxylic acid in total enzymic hydrolysates of peptides and glycopeptides by gas–liquid chromatography

PubMed Central

Hediger, Hedy; Stevens, Richard L.; Brandenberger, Hans; Schmid, Karl

1973-01-01

A new procedure for the qualitative and quantitative determination of asparagine, glutamine and pyrrolidonecarboxylic acid in total enzymic hydrolysates of peptides and glycopeptides based on g.l.c. has been developed. Under the conditions of esterification and trifluoroacetylation N-trifluoroacetylaspartic acid mono-n-butyl ester was formed from asparagine and N-trifluoroacetylglutamic acid mono-n-butyl ester from both glutamine and pyrrolidonecarboxylic acid. To distinguish between the latter two compounds, the esterification was carried out at room temperature yielding 30% of esterified pyrrolidonecarboxylic acid but less than 1% of esterified glutamine. In extending the g.l.c. of amino acids, the previously unknown positions in the g.l.c. elution pattern of the following amino acids could also be reproducibly determined: carboxymethylcysteine, homoserine, hydroxylysine and ∈-methyl-lysine. Further, certain glycopeptides were investigated and the artifacts due to their carbohydrate moieties were determined. PMID:4733240

Crystal Structure of StaL, A Glycopeptide Antibiotic Sulfotransferase from Streptomyces Toyocaensis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi,R.; Lamb, S.; Bhat, S.

2007-01-01

Over the past decade, antimicrobial resistance has emerged as a major public health crisis. Glycopeptide antibiotics such as vanco-mycin and teicoplanin are clinically important for the treatment of Gram-positive bacterial infections. StaL is a 3'-phosphoadenosine 5'-phosphosulfate-dependent sulfotransferase capable of sulfating the cross-linked heptapeptide substrate both in vivo and in vitro, yielding the product A47934 [GenBank], unique teicoplanin-class glycopeptide antibiotic. The sulfonation reaction catalyzed by StaL constitutes the final step in A47934 [GenBank] biosynthesis. Here we report the crystal structure of StaL and its complex with the cofactor product 3'-phosphoadenosine 5'-phosphate. This is only the second prokaryotic sulfotransferase to be structurallymore » characterized. StaL belongs to the large sulfotransferase family and shows higher similarity to cytosolic sulfotransferases (ST) than to the bacterial ST (Stf0). StaL has a novel dimerization motif, different from any other STs that have been structurally characterized. We have also applied molecular modeling to investigate the binding mode of the unique substrate, desulfo-A47934. Based on the structural analysis and modeling results, a series of residues was mutated and kinetically characterized. In addition to the conserved residues (Lys{sup 12}, His{sup 67}, and Ser{sup 98}), molecular modeling, fluorescence quenching experiments, and mutagenesis studies identified several other residues essential for substrate binding and/or activity, including Trp{sup 34}, His{sup 43}, Phe{sup 77}, Trp{sup 132}, and Glu{sup 205}.« less

Comparison of HPLC/ESI-FTICR MS Versus MALDI-TOF/TOF MS for Glycopeptide Analysis of a Highly Glycosylated HIV Envelope Glycoprotein

PubMed Central

Irungu, Janet; Go, Eden P.; Zhang, Ying; Dalpathado, Dilusha S.; Liao, Hua-Xin; Haynes, Barton F.; Desaire, Heather

2013-01-01

Defining the structures and locations of the glycans attached on secreted proteins and virus envelope proteins is important in understanding how glycosylation affects their biological properties. Glycopeptide mass spectrometry (MS)-based analysis is a very powerful, emerging approach to characterize glycoproteins, in which glycosylation sites and the corresponding glycan structures are elucidated in a single MS experiment. However, to date there is not a consensus regarding which mass spectrometric platform provides the best glycosylation coverage information. Herein, we employ two of the most widely used MS approaches, online high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI-MS) and offline HPLC followed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), to determine which of the two approaches provides the best glycosylation coverage information of a complex glycoprotein, the group M consensus HIV-1 envelope, CON-S gp140ΔCFI, which has 31 potential glycosylation sites. Our results highlight differences in the informational content obtained between the two methods such as the overall number of glycosylation sites detected, the numbers of N-linked glycans present at each site, and the type of confirmatory information obtained about the glycopeptide using MS/MS experiments. The two approaches are quite complementary, both in their coverage of glycopeptides and in the information they provide in MS/MS experiments. The information in this study contributes to the field of mass spectrometry by demonstrating the strengths and limitations of two widely used MS platforms in glycoprotein analysis. PMID:18565761

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

PubMed Central

2012-01-01

Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted. PMID:22891821

Obesity-induced decreases in muscle performance are not reversed by weight loss.

PubMed

Seebacher, F; Tallis, J; McShea, K; James, R S

2017-08-01

Obesity can affect muscle phenotypes, and may thereby constrain movement and energy expenditure. Weight loss is a common and intuitive intervention for obesity, but it is not known whether the effects of obesity on muscle function are reversible by weight loss. Here we tested whether obesity-induced changes in muscle metabolic and contractile phenotypes are reversible by weight loss. We used zebrafish (Danio rerio) in a factorial design to compare energy metabolism, locomotor capacity, muscle isometric force and work-loop power output, and myosin heavy chain (MHC) composition between lean fish, diet-induced obese fish, and fish that were obese and then returned to lean body mass following diet restriction. Obesity increased resting metabolic rates (P<0.001) and decreased maximal metabolic rates (P=0.030), but these changes were reversible by weight loss, and were not associated with changes in muscle citrate synthase activity. In contrast, obesity-induced decreases in locomotor performance (P=0.0034), and isolated muscle isometric stress (P=0.01), work-loop power output (P<0.001) and relaxation rates (P=0.012) were not reversed by weight loss. Similarly, obesity-induced decreases in concentrations of fast and slow MHCs, and a shift toward fast MHCs were not reversed by weight loss. Obesity-induced changes in locomotor performance and muscle contractile function were not reversible by weight loss. These results show that weight loss alone may not be a sufficient intervention.

Hypothalamic ghrelin signalling mediates olanzapine-induced hyperphagia and weight gain in female rats.

PubMed

Zhang, Qingsheng; He, Meng; Deng, Chao; Wang, Hongqin; Lian, Jiamei; Huang, Xu-Feng

2014-05-01

Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from hyperphagia.

Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass.

PubMed

Bourron, Olivier; Ciangura, Cécile; Bouillot, Jean-Luc; Massias, Laurent; Poitou, Christine; Oppert, Jean-Michel

2007-11-01

Gastric bypass is increasingly used in morbidly obese patients to achieve significant reduction of body weight and fat mass and concurrent improvement in co-morbidities. We report the case of a 53-year-old male patient (141 kg, BMI 50 kg/m2), successfully treated by amiodarone for supraventricular arrythmia, who underwent Roux-en-Y gastric bypass (RYGBP). 6 months after surgery, he had lost 45% of his preoperative weight (44.8% of weight loss was lean mass) and developed amiodarone-induced subclinical hyperthyroidism. We hypothesize the following sequence of events: weight loss after RYGBP, therefore fat loss, decrease in distribution volume of amiodarone inducing iodine overload and hyperthyroidism, reinforcing weight loss and particularly loss of lean mass. This report emphasizes the importance of careful monitoring of weight and body composition changes after RYGBP. In this situation, checking thyroid status is recommended, especially when there is a history of thyroid disease or potentially toxic thyroid medication.

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

PubMed Central

Burford, B; Gentry-Maharaj, A; Graham, R; Allen, D; Pedersen, J W; Nudelman, A S; Blixt, O; Fourkala, E O; Bueti, D; Dawnay, A; Ford, J; Desai, R; David, L; Trinder, P; Acres, B; Schwientek, T; Gammerman, A; Reis, C A; Silva, L; Osório, H; Hallett, R; Wandall, H H; Mandel, U; Hollingsworth, M A; Jacobs, I; Fentiman, I; Clausen, H; Taylor-Papadimitriou, J; Menon, U; Burchell, J M

2013-01-01

Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection. PMID:23652307

Quinolone and Glycopeptide Therapy for Infection in Mouse Following Exposure to Mixed-Field Neutron-Gamma-Photon Radiation

DTIC Science & Technology

1993-01-01

prevents mortality, the addition of a glycopeptide can gens such as Staphylococcus spp., evaluating the enhance systemic infection by resistant...bacteria 35 10 15- 20 25 30 60 (including six E.faecalis and five Staphylococcus aureus) L IJ Days (Table 3). Treatment In the third experiment the...5.00 and 5.25Gy and most Staphylococcus spp. were of Streplococcus spp. increased. 3.3. Antimicrobial serum concentrations Antimicrobial serum

Glycopeptide Resistance vanA Operons in Paenibacillus Strains Isolated from Soil

PubMed Central

Guardabassi, Luca; Perichon, Bruno; van Heijenoort, Jean; Blanot, Didier; Courvalin, Patrice

2005-01-01

The sequence and gene organization of the van operons in vancomycin (MIC of >256 μg/ml)- and teicoplanin (MIC of ≥32 μg/ml)-resistant Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B isolated from soil were determined. Both operons had regulatory (vanR and vanS), resistance (vanH, vanA, and vanX), and accessory (vanY, vanZ, and vanW) genes homologous to the corresponding genes in enterococcal vanA and vanB operons. The vanAPT operon in P. thiaminolyticus PT-2B1 had the same gene organization as that of vanA operons whereas vanAPA in P. apiarius PA-B2B resembled vanB operons due to the presence of vanW upstream from the vanHAX cluster but was closer to vanA operons in sequence. Reference P. apiarius strains NRRL B-4299 and NRRL B-4188 were found to harbor operons indistinguishable from vanAPA by PCR mapping, restriction fragment length polymorphism, and partial sequencing, suggesting that this operon was species specific. As in enterococci, resistance was inducible by glycopeptides and associated with the synthesis of pentadepsipeptide peptidoglycan precursors ending in d-Ala-d-Lac, as demonstrated by d,d-dipeptidase activities, high-pressure liquid chromatography, and mass spectrometry. The precursors differed from those in enterococci by the presence of diaminopimelic acid instead of lysine in the peptide chain. Altogether, the results are compatible with the notion that van operons in soil Paenibacillus strains and in enterococci have evolved from a common ancestor. PMID:16189102

Glycopeptide resistance vanA operons in Paenibacillus strains isolated from soil.

PubMed

Guardabassi, Luca; Perichon, Bruno; van Heijenoort, Jean; Blanot, Didier; Courvalin, Patrice

2005-10-01

The sequence and gene organization of the van operons in vancomycin (MIC of >256 microg/ml)- and teicoplanin (MIC of > or =32 microg/ml)-resistant Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B isolated from soil were determined. Both operons had regulatory (vanR and vanS), resistance (vanH, vanA, and vanX), and accessory (vanY, vanZ, and vanW) genes homologous to the corresponding genes in enterococcal vanA and vanB operons. The vanA(PT) operon in P. thiaminolyticus PT-2B1 had the same gene organization as that of vanA operons whereas vanA(PA) in P. apiarius PA-B2B resembled vanB operons due to the presence of vanW upstream from the vanHAX cluster but was closer to vanA operons in sequence. Reference P. apiarius strains NRRL B-4299 and NRRL B-4188 were found to harbor operons indistinguishable from vanA(PA) by PCR mapping, restriction fragment length polymorphism, and partial sequencing, suggesting that this operon was species specific. As in enterococci, resistance was inducible by glycopeptides and associated with the synthesis of pentadepsipeptide peptidoglycan precursors ending in D-Ala-D-Lac, as demonstrated by D,D-dipeptidase activities, high-pressure liquid chromatography, and mass spectrometry. The precursors differed from those in enterococci by the presence of diaminopimelic acid instead of lysine in the peptide chain. Altogether, the results are compatible with the notion that van operons in soil Paenibacillus strains and in enterococci have evolved from a common ancestor.

Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats.

PubMed

Devenny, James J; Godonis, Helen E; Harvey, Susan J; Rooney, Suzanne; Cullen, Mary J; Pelleymounter, Mary Ann

2012-08-01

Dapagliflozin is a potent and selective sodium glucose cotransporter-2 (SGLT2) inhibitor which promotes urinary glucose excretion and induces weight loss. Since metabolic compensation can offset a negative energy balance, we explored the potential for a compensatory physiological response to the weight loss induced by dapagliflozin. Dapagliflozin was administered (0.5-5 mpk; p.o.) to diet-induced obese (DIO) rats with or without ad libitum access to food for 38 days. Along with inducing urinary glucose excretion, chronic administration of dapagliflozin dose-dependently increased food and water intake relative to vehicle-treated controls. Despite this, it reduced body weight by 4% (relative to controls) at the highest dose. The degree of weight loss was increased by an additional 9% if hyperphagia was prevented by restricting food intake to that of vehicle controls. Neither oxygen consumption (vO2) or the respiratory exchange ratio (RER) were altered by dapagliflozin treatment alone. Animals treated with dapagliflozin and pair-fed to vehicle controls (5 mpk PF-V) showed a reduction in RER and an elevation in nonfasting β-hydroxybutyrate (BHBA) relative to ad libitum-fed 5 mpk counterparts. Fasting BHBA was elevated in the 1 mpk, 5 mpk, and 5 mpk PF-V groups. Serum glucose was reduced in the fasted, but not the unfasted state. Insulin was reduced in the non-fasted state. These data suggest that in rodents, the persistent urinary glucose excretion induced by dapagliflozin was accompanied by compensatory hyperphagia, which attenuated the weight loss induced by SGLT2 inhibition. Therefore, it is possible that dapagliflozin-induced weight loss could be enhanced with dietary intervention.

Clozapine-induced dysphagia with secondary substantial weight loss.

PubMed

Osman, Mugtaba; Devadas, Vekneswaran

2016-08-19

Dysphagia is listed as a 'rare' side effect following clozapine treatment. In this case report, we describe how significant clozapine-induced dysphagia has led to significant reduction of nutritional intake with subsequent substantial weight loss. An 18-year-old single man with an established diagnosis of treatment-resistant paranoid schizophrenia recovered well on a therapeutic dose of clozapine. However, he was noted to lose weight significantly (up to 20% of his original weight) as the dose was uptitrated. This was brought about by development of dysphagia, likely to be due to clozapine. Addition of nutritional supplementary liquids and initiation of a modified behavioural dietary/swallowing programme, while repeatedly mastering the Mendelsohn manoeuvre technique, alleviated the swallowing difficulties and restored his weight. 2016 BMJ Publishing Group Ltd.

Excitatory Hindbrain–Forebrain Communication Is Required for Cisplatin-Induced Anorexia and Weight Loss

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Zheng, Huiyuan; Rinaman, Linda; Grill, Harvey J.

2017-01-01

Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN) and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation. To test whether lPBN→CeA projection neurons are required for cisplatin-induced anorexia and weight loss, we inhibited these neurons chemogenetically using a retrograde Cre-recombinase-expressing canine adenovirus-2 in combination with Cre-dependent inhibitory Designer Receptors Exclusive Activated by Designer Drugs (DREADDs) before cisplatin treatment. Inhibition of lPBN→CeA neurons attenuated cisplatin-induced anorexia and body weight loss significantly. Using a similar approach, we additionally demonstrated that inhibition of NTS→lPBN neurons attenuated cisplatin-induced anorexia and body weight loss significantly. Together, our data support the view that excitatory hindbrain–forebrain projections are necessary for cisplatin's untoward effects on energy intake, elucidating a key neuroanatomical circuit driving pathological anorexia and weight loss that accompanies chemotherapy treatment. SIGNIFICANCE STATEMENT Chemotherapy treatments are commonly used to treat cancers despite accompanying anorexia and weight loss that may limit treatment adherence and reduce patient quality of life. Strikingly, we lack a neural understanding of, and effective treatments for, chemotherapy-induced anorexia and weight

Preparation of hydrophilic monolithic capillary column by in situ photo-polymerization of N-vinyl-2-pyrrolidinone and acrylamide for highly selective and sensitive enrichment of N-linked glycopeptides.

PubMed

Jiang, Hao; Yuan, Huiming; Qu, Yanyan; Liang, Yu; Jiang, Bo; Wu, Qi; Deng, Nan; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

2016-01-01

In this study, a novel kind of amide functionalized hydrophilic monolith was synthesized by the in situ photo-polymerization of N-vinyl-2-pyrrolidinone (NVP), acrylamide (AM), and N, N'-methylenebisacrylamide (MBA) in a UV transparent capillary, and successfully applied for hydrophilic interaction chromatography (HILIC) based enrichment of N-linked glycopeptides. With 2 μg of the tryptic digests of IgG as the sample, after enrichment, 18 glycopeptides could be identified by MALDI-TOF/TOF MS analysis. Furthermore, with the mixture of BSA and IgG digests (10,000:1, m/m) as the sample, 6 N-linked glycopeptides were unambiguously identified after enrichment, indicating the high selectivity and good specificity of such material. Moreover, such a monolithic capillary column was also applied for the N-glycosylation sites profiling of 6 μg protein digests from HeLa cells and 1 μL human serum. In total, 530 and 262 unique N-glycosylated peptides were identified, respectively, corresponding to 282 and 124N-glycoproteins, demonstrating its great potential for the large scale glycoproteomics analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study.

PubMed

Wadden, T A; Hollander, P; Klein, S; Niswender, K; Woo, V; Hale, P M; Aronne, L

2013-11-01

Liraglutide, a once-daily human glucagon-like peptide-1 analog, induced clinically meaningful weight loss in a phase 2 study in obese individuals without diabetes. The present randomized phase 3 trial assessed the efficacy of liraglutide in maintaining weight loss achieved with a low-calorie diet (LCD). Obese/overweight participants (≥18 years, body mass index ≥30 kg m(-2) or ≥27 kg m(-2) with comorbidities) who lost ≥5% of initial weight during a LCD run-in were randomly assigned to liraglutide 3.0 mg per day or placebo (subcutaneous administration) for 56 weeks. Diet and exercise counseling were provided throughout the trial. Co-primary end points were percentage weight change from randomization, the proportion of participants that maintained the initial ≥5% weight loss, and the proportion that lost ≥5% of randomization weight (intention-to-treat analysis). ClinicalTrials.gov identifier: NCT00781937. Participants (n=422) lost a mean 6.0% (s.d. 0.9) of screening weight during run-in. From randomization to week 56, weight decreased an additional mean 6.2% (s.d. 7.3) with liraglutide and 0.2% (s.d. 7.0) with placebo (estimated difference -6.1% (95% class intervals -7.5 to -4.6), P<0.0001). More participants receiving liraglutide (81.4%) maintained the ≥5% run-in weight loss, compared with those receiving placebo (48.9%) (estimated odds ratio 4.8 (3.0; 7.7), P<0.0001), and 50.5% versus 21.8% of participants lost ≥5% of randomization weight (estimated odds ratio 3.9 (2.4; 6.1), P<0.0001). Liraglutide produced small but statistically significant improvements in several cardiometabolic risk factors compared with placebo. Gastrointestinal (GI) disorders were reported more frequently with liraglutide than placebo, but most events were transient, and mild or moderate in severity. Liraglutide, with diet and exercise, maintained weight loss achieved by caloric restriction and induced further weight loss over 56 weeks. Improvements in some

Metformin for olanzapine-induced weight gain: a systematic review and meta-analysis.

PubMed

Praharaj, Samir Kumar; Jana, Amlan Kusum; Goyal, Nishant; Sinha, Vinod Kumar

2011-03-01

Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n= 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P= 0.00002, I(2) = 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m(-2) lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity

PubMed Central

Pepino, Marta Yanina; Stein, Richard I.; Eagon, J. Christopher; Klein, Samuel

2014-01-01

Objective To test the hypotheses that bariatric surgery-induced weight loss: 1) induces remission of food addiction (FA), and 2) normalizes other eating behaviors associated with FA. Design and Methods Forty-four obese subjects (BMI= 48±8 kg/m2) were studied before and after ~20% weight loss induced by bariatric surgery (25 Roux-en-Y gastric bypass, 11 laparoscopic adjustable gastric banding, and 8 sleeve gastrectomy). We assessed: 1) FA (Yale Food Addiction Scale), 2) food cravings (Food Craving Inventory) and 3) restrictive, emotional and external eating behaviors (Dutch Eating Behavior Questionnaire). Results FA was identified in 32% of subjects before surgery. Compared with non-FA subjects, those with FA craved foods more frequently, and had higher scores for emotional and external eating behaviors (all P-values <0.01; all Cohen’s d >0.8). Surgery-induced weight loss resulted in remission of FA in 93% of FA subjects; no new cases of FA developed after surgery. Surgery-induced weight loss decreased food cravings, and emotional and external eating behaviors in both groups (all P-values <0.001; all Cohen’s d≥0.8). Restrictive eating behavior did not change in non-FA subjects but increased in FA subjects (P<0.01; Cohen’s d>1.1). Conclusion Bariatric surgery-induced weight loss induces remission of FA and improves several eating behaviors that are associated with FA. PMID:24852693

Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity.

PubMed

Pepino, Marta Yanina; Stein, Richard I; Eagon, J Christopher; Klein, Samuel

2014-08-01

To test the hypotheses that bariatric surgery-induced weight loss: induces remission of food addiction (FA), and normalizes other eating behaviors associated with FA. Forty-four obese subjects (BMI= 48 ± 8 kg/m(2) ) were studied before and after ∼20% weight loss induced by bariatric surgery (25 Roux-en-Y gastric bypass, 11 laparoscopic adjustable gastric banding, and eight sleeve gastrectomy). We assessed: FA (Yale Food Addiction Scale), food cravings (Food Craving Inventory), and restrictive, emotional and external eating behaviors (Dutch Eating Behavior Questionnaire). FA was identified in 32% of subjects before surgery. Compared with non-FA subjects, those with FA craved foods more frequently, and had higher scores for emotional and external eating behaviors (all P-values <0.01; all Cohen's d >0.8). Surgery-induced weight loss resulted in remission of FA in 93% of FA subjects; no new cases of FA developed after surgery. Surgery-induced weight loss decreased food cravings, and emotional and external eating behaviors in both groups (all P-values < 0.001; all Cohen's d ≥ 0.8). Restrictive eating behavior did not change in non-FA subjects but increased in FA subjects (P < 0.01; Cohen's d>1.1). Bariatric surgery-induced weight loss induces remission of FA and improves several eating behaviors that are associated with FA. Copyright © 2014 The Obesity Society.

The size-weight illusion induced through human echolocation.

PubMed

Buckingham, Gavin; Milne, Jennifer L; Byrne, Caitlin M; Goodale, Melvyn A

2015-02-01

Certain blind individuals have learned to interpret the echoes of self-generated sounds to perceive the structure of objects in their environment. The current work examined how far the influence of this unique form of sensory substitution extends by testing whether echolocation-induced representations of object size could influence weight perception. A small group of echolocation experts made tongue clicks or finger snaps toward cubes of varying sizes and weights before lifting them. These echolocators experienced a robust size-weight illusion. This experiment provides the first demonstration of a sensory substitution technique whereby the substituted sense influences the conscious perception through an intact sense. © The Author(s) 2014.

Accuracy of the VITEK 2 System To Detect Glycopeptide Resistance in Enterococci

PubMed Central

van den Braak, Nicole; Goessens, Wil; van Belkum, Alex; Verbrugh, Henri A.; Endtz, Hubert P.

2001-01-01

We evaluated the accuracy of the VITEK 2 fully automated system to detect and identify glycopeptide-resistant enterococci (GRE) compared to a reference agar dilution method. The sensitivity of vancomycin susceptibility testing with VITEK 2 for the detection of vanA, vanB, and vanC1 strains was 100%. The sensitivity of vancomycin susceptibility testing of vanC2 strains was 77%. The sensitivity of teicoplanin susceptibility testing of vanA strains was 90%. Of 80 vanC enterococci, 78 (98%) were correctly identified by VITEK 2 as Enterococcus gallinarum/Enterococcus casseliflavus. Since the identification and susceptibility data are produced within 3 and 8 h, respectively, VITEK 2 appears a fast and reliable method for detection of GRE in microbiology laboratories. PMID:11136798

The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum.

PubMed

Sun, Li-Xin; Lin, Zhi-Bin; Lu, Jie; Li, Wei-Dong; Niu, Yan-Dong; Sun, Yu; Hu, Chen-Yang; Zhang, Guo-Qiang; Duan, Xin-Suo

2017-06-01

Ganoderma lucidum (Fr.) Karst (Ganodermataceae) is a medicinal mushroom that has been extensively used in China for centuries to promote longevity and improve vigor without significant adverse effects. There is continuous interest in the bioactive properties of G. lucidum in view of its newly developed popularity in other regions besides Asia, such as Europe. Glycopeptide derived from G. lucidum (Gl-PS) is one of the main effective components isolated from this mushroom. The Gl-PS has been demonstrated pleiotropic with many bioactivities including immunomodulatory and antitumor effects. Macrophages are important cells involved in innate and adaptive immunity. Classically activated macrophages (M1) and alternatively activated macrophages (M2), with their different roles, display distinct cytokine profiles: M1 preferentially produces TNF-α, IL-6, and IL-12; conversely, M2 generates more IL-10 and arginase. Gl-PS might have the potential to promote macrophage M1 polarization by lipopolysaccharide (LPS). In this study, LPS was used to induce the M1 polarization. It was shown that the level of the TNF-α, IL-6, and IL-12 were increased and the IL-10 and arginase I were decreased in the polarized M1 macrophages after application of Gl-PS compared to the control. The results indicated the potential of Gl-PS to promote M1 polarization vs M2, with the health beneficial understanding of the bioactivities of Gl-PS.

Excitatory Hindbrain-Forebrain Communication Is Required for Cisplatin-Induced Anorexia and Weight Loss.

PubMed

Alhadeff, Amber L; Holland, Ruby A; Zheng, Huiyuan; Rinaman, Linda; Grill, Harvey J; De Jonghe, Bart C

2017-01-11

Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN) and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation. To test whether lPBN→CeA projection neurons are required for cisplatin-induced anorexia and weight loss, we inhibited these neurons chemogenetically using a retrograde Cre-recombinase-expressing canine adenovirus-2 in combination with Cre-dependent inhibitory Designer Receptors Exclusive Activated by Designer Drugs (DREADDs) before cisplatin treatment. Inhibition of lPBN→CeA neurons attenuated cisplatin-induced anorexia and body weight loss significantly. Using a similar approach, we additionally demonstrated that inhibition of NTS→lPBN neurons attenuated cisplatin-induced anorexia and body weight loss significantly. Together, our data support the view that excitatory hindbrain-forebrain projections are necessary for cisplatin's untoward effects on energy intake, elucidating a key neuroanatomical circuit driving pathological anorexia and weight loss that accompanies chemotherapy treatment. Chemotherapy treatments are commonly used to treat cancers despite accompanying anorexia and weight loss that may limit treatment adherence and reduce patient quality of life. Strikingly, we lack a neural understanding of, and effective treatments for, chemotherapy-induced anorexia and weight loss. The current data

Antipsychotic-induced weight gain: a comprehensive research synthesis.

PubMed

Allison, D B; Mentore, J L; Heo, M; Chandler, L P; Cappelleri, J C; Infante, M C; Weiden, P J

1999-11-01

The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.

The Effect of Ranitidine on Olanzapine-Induced Weight Gain

PubMed Central

Ranjbar, Fatemeh; Ghanepour, Alireza; Asadlo, Mahbob; Alizadeh, Amineh

2013-01-01

Induced weight gain is a disturbing side effect of Olanzapine that affects the quality of life in psychotic patients. The aim of this study was to assess the efficacy of Ranitidine in attenuating or preventing Olanzapine-induced weight gain. A parallel 2-arm clinical trial was done on 52 patients with schizophrenia, schizoaffective and schizophreniform disorders who received Olanzapine for the first time. All these were first-episode admitted patients. They were randomly allocated to receive either Ranitidine or placebo. The trend of body mass index (BMI) was compared between groups over 16-week course of treatment. Mean weight was 62.3 (SD: 9.6) kg at baseline. Thirty-three subjects (63.5%) had positive family history of obesity. The average BMI increment was 1.1 for Ranitidine group and 2.4 for the placebo group. The multivariate analysis showed this effect to be independent of sex, family history of obesity, and baseline BMI value. The longitudinal modeling after controlling for baseline values failed to show the whole trend slope to be different. Although the slight change in trend's slope puts forward a hypothesis that combined use of Ranitidine and Olanzapine may attenuate the weight gain long run, this needs to be retested in future larger scale long-term studies. This trial is registered with IRCT.ir 201009112181N5. PMID:23984393

The effect of ranitidine on olanzapine-induced weight gain.

PubMed

Ranjbar, Fatemeh; Ghanepour, Alireza; Sadeghi-Bazargani, Homayoun; Asadlo, Mahbob; Alizadeh, Amineh

2013-01-01

Induced weight gain is a disturbing side effect of Olanzapine that affects the quality of life in psychotic patients. The aim of this study was to assess the efficacy of Ranitidine in attenuating or preventing Olanzapine-induced weight gain. A parallel 2-arm clinical trial was done on 52 patients with schizophrenia, schizoaffective and schizophreniform disorders who received Olanzapine for the first time. All these were first-episode admitted patients. They were randomly allocated to receive either Ranitidine or placebo. The trend of body mass index (BMI) was compared between groups over 16-week course of treatment. Mean weight was 62.3 (SD: 9.6) kg at baseline. Thirty-three subjects (63.5%) had positive family history of obesity. The average BMI increment was 1.1 for Ranitidine group and 2.4 for the placebo group. The multivariate analysis showed this effect to be independent of sex, family history of obesity, and baseline BMI value. The longitudinal modeling after controlling for baseline values failed to show the whole trend slope to be different. Although the slight change in trend's slope puts forward a hypothesis that combined use of Ranitidine and Olanzapine may attenuate the weight gain long run, this needs to be retested in future larger scale long-term studies. This trial is registered with IRCT.ir 201009112181N5.

Weight Loss Decreases Inherent and Allergic Methacholine Hyperresponsiveness in Mouse Models of Diet-Induced Obese Asthma

PubMed Central

Ather, Jennifer L.; Chung, Michael; Hoyt, Laura R.; Randall, Matthew J.; Georgsdottir, Anna; Daphtary, Nirav A.; Aliyeva, Minara I.; Suratt, Benjamin T.; Bates, Jason H. T.; Irvin, Charles G.; Russell, Sheila R.; Forgione, Patrick M.; Dixon, Anne E.

2016-01-01

Obese asthma presents with inherent hyperresponsiveness to methacholine or augmented allergen-driven allergic asthma, with an even greater magnitude of methacholine hyperresponsiveness. These physiologic parameters and accompanying obese asthma symptoms can be reduced by successful weight loss, yet the underlying mechanisms remain incompletely understood. We implemented mouse models of diet-induced obesity, dietary and surgical weight loss, and environmental allergen exposure to examine the mechanisms and mediators of inherent and allergic obese asthma. We report that the methacholine hyperresponsiveness in these models of inherent obese asthma and obese allergic asthma manifests in distinct anatomical compartments but that both are amenable to interventions that induce substantial weight loss. The inherent obese asthma phenotype, with characteristic increases in distal airspace tissue resistance and tissue elastance, is associated with elevated proinflammatory cytokines that are reduced with dietary weight loss. Surprisingly, bariatric surgery–induced weight loss further elevates these cytokines while reducing methacholine responsiveness to levels similar to those in lean mice or in formerly obese mice rendered lean through dietary intervention. In contrast, the obese allergic asthma phenotype, with characteristic increases in central airway resistance, is not associated with increased adaptive immune responses, yet diet-induced weight loss reduces methacholine hyperresponsiveness without altering immunological variables. Diet-induced weight loss is effective in models of both inherent and allergic obese asthma, and our examination of the fecal microbiome revealed that the obesogenic Firmicutes/Bacteroidetes ratio was normalized after diet-induced weight loss. Our results suggest that structural, immunological, and microbiological factors contribute to the manifold presentations of obese asthma. PMID:27064658

Efficacy of ranitidine in olanzapine-induced weight gain: a dose-response study.

PubMed

Mehta, Varun S; Ram, Daya

2016-12-01

Weight gain has long been recognized as a side-effect of atypical antipsychotic drugs. Numerous new approaches have been tried for prevention of weight gain, the H2 blockers being one of them. The study was conducted with the aim to evaluate the efficacy of ranitidine in olanzapine-induced weight gain at two fixed doses of 150 and 300 mg day -1 . Seventy-five inpatients with an ICD-10-DCR diagnosis of schizophrenia as their first episode were randomized into three groups of 25 patients each, receiving 150 mg day -1 ranitidine, 300 mg day -1 ranitidine and third group receiving only olanzapine. Their weight and body mass index (BMI) were measured at baseline and at intervals of 4 and 8 weeks. All patients were comparable with respect to their weight and BMI at baseline. When a change in the weight and BMI was assessed at 4 and 8 weeks from baseline, no significant difference was observed between the three groups. Ranitidine at doses of 150 and 300 mg day -1 when combined with olanzapine was ineffective in attenuating olanzapine-induced weight gain. The likely reasons could be the use of low doses for a shorter period of time, or mechanisms other than H2 receptors might play an important role in weight gain. © 2014 Wiley Publishing Asia Pty Ltd.

Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

PubMed

Turánek, Jaroslav; Ledvina, Miroslav; Kasná, Andrea; Vacek, Antonín; Hríbalova, Vera; Krejcí, Josef; Miller, Andrew D

2006-04-12

The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

Physiological mechanisms of sustained fumagillin-induced weight loss.

PubMed

An, Jie; Wang, Liping; Patnode, Michael L; Ridaura, Vanessa K; Haldeman, Jonathan M; Stevens, Robert D; Ilkayeva, Olga; Bain, James R; Muehlbauer, Michael J; Glynn, Erin L; Thomas, Steven; Muoio, Deborah; Summers, Scott A; Vath, James E; Hughes, Thomas E; Gordon, Jeffrey I; Newgard, Christopher B

2018-03-08

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by gut microbiota, and caloric spilling in the urine. Studies in gnotobiotic mice reveal that effects of fumagillin on energy expenditure but not feeding behavior may be mediated by the gut microbiota. In sum, fumagillin engages weight loss-inducing behavioral and physiologic circuits distinct from those activated by simple caloric restriction.

Physiological mechanisms of sustained fumagillin-induced weight loss

PubMed Central

An, Jie; Patnode, Michael L.; Haldeman, Jonathan M.; Stevens, Robert D.; Ilkayeva, Olga; Bain, James R.; Muehlbauer, Michael J.; Glynn, Erin L.; Thomas, Steven; Muoio, Deborah; Summers, Scott A.; Vath, James E.; Hughes, Thomas E.; Gordon, Jeffrey I.; Newgard, Christopher B.

2018-01-01

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by gut microbiota, and caloric spilling in the urine. Studies in gnotobiotic mice reveal that effects of fumagillin on energy expenditure but not feeding behavior may be mediated by the gut microbiota. In sum, fumagillin engages weight loss–inducing behavioral and physiologic circuits distinct from those activated by simple caloric restriction. PMID:29515039

A systematic review of the interrelation between diet- and surgery-induced weight loss and vitamin D status.

PubMed

Himbert, Caroline; Ose, Jennifer; Delphan, Mahmoud; Ulrich, Cornelia M

2017-02-01

Obesity is a major global health problem and has been associated with vitamin D deficiency. Intentional weight loss may alter vitamin D status and, conversely, vitamin D supplementation has been hypothesized to aid in weight loss. A systematic literature search in PubMed/Medline identified 3173 articles of which 37 studies (randomized controlled trials (RCT) [n=17], non-RCTs [n=20]) are summarized as effect of: (I) diet-induced weight loss on vitamin D status (n=7), (II) vitamin D supplementation on diet-induced weight loss (n=11), (III) surgery-induced weight loss on vitamin D status (n=15), and (IV) vitamin D supplementation after surgery-induced weight loss on vitamin D status (n=5). While all studies on the effect of diet-induced weight loss on vitamin D status have consistently reported increased vitamin D levels, the targeted percentage of weight loss that is necessary for an increase has varied between 5% and >10%. N=11 RCTs testing the effect of vitamin D supplementation observe that vitamin D supplementation does not result in increased weight loss, but may affect body fat loss. Vitamin D deficiency and subsequent hyperparathyroidism have been detected in post-surgery patients, and there is evidence that vitamin D supplementation improves these post-surgery complications. We review the current evidence addressing the role of vitamin D status and supplementation in diet- and surgery-induced weight loss. Subsequently, we highlight gaps in current research and suggest directions for future research including differences in vitamin D supplementation dosages, indoor vs. outdoor exercise, and the assessment of vitamin D status in different body pools. Published by Elsevier Inc.

In Vitro Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic, against 377 Strains of Anaerobic Bacteria and 34 Strains of Corynebacterium Species

PubMed Central

Citron, Diane M.; Warren, Yumi A.; Goldstein, Ellie J. C.

2012-01-01

TD-1792 is a multivalent glycopeptide-cephalosporin heterodimer antibiotic with potent activity against Gram-positive bacteria. We tested TD-1792 against 377 anaerobes and 34 strains of Corynebacterium species. Against nearly all Gram-positive strains, TD-1792 had an MIC90 of 0.25 μg/ml and was typically 3 to 7 dilutions more active than vancomycin and daptomycin. PMID:22290981

Persistence of Animal and Human Glycopeptide-Resistant Enterococci on Two Norwegian Poultry Farms Formerly Exposed to Avoparcin Is Associated with a Widespread Plasmid-Mediated vanA Element within a Polyclonal Enterococcus faecium Population

PubMed Central

Johnsen, P. J.; Østerhus, J. I.; Sletvold, H.; Sørum, M.; Kruse, H.; Nielsen, K.; Simonsen, G. S.; Sundsfjord, A.

2005-01-01

The evolutionary processes responsible for the long-term persistence of glycopeptide-resistant Enterococcus faecium (GREF) in nonselective environments were addressed by genetic analyses of E. faecium populations in animals and humans on two Norwegian poultry farms that were previously exposed to avoparcin. A total of 222 fecal GREF (n = 136) and glycopeptide-susceptible (n = 86) E. faecium (GSEF) isolates were obtained from farmers and poultry on three separate occasions in 1998 and 1999. Pulsed-field gel electrophoresis (PFGE) and plasmid DNA analyses discerned 22 GREF and 32 GSEF PFGE types within shifting polyclonal animal and human E. faecium populations and indicated the presence of transferable plasmid-mediated vanA resistance, respectively. Examples of dominant, persistent GREF PFGE types supported the notion that environmentally well-adapted GREF types may counteract the reversal of resistance. PFGE analyses, sequencing of the purK housekeeping gene, and partial typing of vanA-containing Tn1546 suggested a common animal and human reservoir of glycopeptide resistance. Inverse PCR amplification and sequence analyses targeting the right end of the Tn1546-plasmid junction fragment strongly indicated the presence of a common single Tn1546-plasmid-mediated element in 20 of 22 GREF PFGE types. This observation was further strengthened by vanY-vanZ hybridization analyses of plasmid DNAs as well as the finding of a physical linkage between Tn1546 and a putative postsegregation killing system for seven GREF PFGE types. In conclusion, our observations suggest that the molecular unit of persistence of glycopeptide resistance is a common mobile plasmid-mediated vanA-containing element within a polyclonal GREF population that changes over time. In addition, we propose that “plasmid addiction systems” may contribute to the persistence of GREF in nonselective environments. PMID:15640183

Quantitative synthesis of genetically encoded glycopeptide libraries displayed on M13 phage.

PubMed

Ng, Simon; Jafari, Mohammad R; Matochko, Wadim L; Derda, Ratmir

2012-09-21

Phage display is a powerful technology that enables the discovery of peptide ligands for many targets. Chemical modification of phage libraries have allowed the identification of ligands with properties not encountered in natural polypeptides. In this report, we demonstrated the synthesis of 2 × 10(8) genetically encoded glycopeptides from a commercially available phage-displayed peptide library (Ph.D.-7) in a two-step, one-pot reaction in <1.5 h. Unlike previous reports, we bypassed genetic engineering of phage. The glycan moiety was introduced via an oxime ligation following oxidation of an N-terminal Ser/Thr; these residues are present in the peptide libraries at 20-30% abundance. The construction of libraries was facilitated by simple characterization, which directly assessed the yield and regioselectivity of chemical reactions performed on phage. This quantification method also allowed facile yield determination of reactions in 10(9) distinct molecules. We envision that the methodology described herein will find broad application in the synthesis of custom chemically modified phage libraries.

Metformin for treatment of antipsychotic-induced weight gain: a randomized, placebo-controlled study.

PubMed

Wang, Man; Tong, Jian-hua; Zhu, Gang; Liang, Guang-ming; Yan, Hong-fei; Wang, Xiu-zhen

2012-06-01

To evaluate the efficacy of metformin for treatment of antipsychotic-induced weight gain. Seventy-two patients with first-episode schizophrenia who gained more than 7% of their predrug weight were randomly assigned to receive 1000 mg/d of metformin or placebo in addition to their ongoing treatment for 12 weeks using a double-blind study design. The primary outcome was change in body weight. The secondary outcomes included changes in body mass index, fasting glucose and insulin, and insulin resistance index. Of the 72 patients who were randomly assigned, 66 (91.6%) completed treatments. The body weight, body mass index, fasting insulin and insulin resistance index decreased significantly in the metformin group, but increased in the placebo group during the 12-week follow-up period. Significantly more patients in the metformin group lost their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight loss. Metformin was tolerated well by majority patients. Metformin was effective and safe in attenuating antipsychotic-induced weight gain and insulin resistance in first-episode schizophrenia patients. Patients displayed good adherence to metformin. Copyright © 2012 Elsevier B.V. All rights reserved.

Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

PubMed Central

Thatcher, Brendan S.; Reidelberger, Roger D.; Ogimoto, Kayoko; Wolden-Hanson, Tami; Baskin, Denis G.; Schwartz, Michael W.; Blevins, James E.

2012-01-01

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fak/fak) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs. PMID:22008455

Prevalence and correlates of self-induced vomiting as weight-control strategy among adolescents in Taiwan.

PubMed

Liou, Yiing Mei; Hsu, Ya-Wen; Ho, Jow-Fei; Lin, Che-Hung; Hsu, Wen-Yen; Liou, Tsan-Hon

2012-01-01

This study was designed to assess the prevalence and correlates of self-induced vomiting to control body weight among adolescents in Taiwan. Over the past decades, the rate of obesity among children in Taiwan has nearly tripled. Educational authorities have devoted considerable effort to prevent the increase in childhood obesity. An observational exploratory design to investigate the problem of using unhealthy weight-reduction strategy. This study consists of a cross-sectional study aimed at collecting national representative data. We chose 120 representative schools using a three-stage stratified systematic sampling design with probability proportionate to the size of the population in Taiwan. Participants consisted of 8673 girls and 7043 boys, aged 10-18 old. Of the participants, 13% reported using self-induced vomiting, the prevalence being highest in participants aged 10-12 (15·9%) and lowest in participants aged 16-18 (7·5%). Several factors were significantly and positively associated with the use of self-induced vomiting as a weight-loss strategy, specifically subjects who (1) watched television, used computer, surfed the Internet or played video games for greater than or equal to two hours/day, (2) consumed fried food every day and (3) ate night-time snacks every day (odds ratio = 1·55, 2·10 and 1·51, respectively; p < 0·05). Eating breakfast every day and sleeping for more than eight hours a day were both protective factors against the use of self-induced vomiting to control body weight (odds ratio = 0·43 and 0·86, respectively; p < 0·05). Self-induced vomiting was prevalent among adolescents who had tried to lose weight; sedentary lifestyle, shorter sleep length and unhealthy eating habits may contribute significantly to this behaviour among these adolescents. School nurses who are helping adolescents lose weight should also pay attention to the possibility they are using self-induced vomiting as a weight-control strategy. © 2011 Blackwell

The Glycan Role in the Glycopeptide Immunogenicity Revealed by Atomistic Simulations and Spectroscopic Experiments on the Multiple Sclerosis Biomarker CSF114(Glc)

NASA Astrophysics Data System (ADS)

Bruno, Agostino; Scrima, Mario; Novellino, Ettore; D'Errico, Gerardino; D'Ursi, Anna Maria; Limongelli, Vittorio

2015-03-01

Glycoproteins are often recognized as not-self molecules by antibodies triggering the onset of severe autoimmune diseases such as Multiple Sclerosis (MS). Thus, the development of antigen-mimicking biomarkers represents an attractive strategy for an early diagnosis of the disease. An example is the synthetic glycopeptide CSF114(Glc), which was designed and tested as MS biomarker and whose clinical application was limited by its reduced ability to detect autoantibodies in MS patients. In the attempt to improve the efficacy of CSF114(Glc), we have characterized all the events leading to the final binding of the biomarker to the autoantibody using atomistic simulations, ESR and NMR experiments. The glycosydic moiety plays a primary role in the whole process. In particular, in an environment mimicking that used in the clinical tests the glycopeptide assumes a α-helix structure that is functional for the interaction with the antibody. In this conformation CSF114(Glc) binds the monoclonal antibody mAb8-18C5 similarly to the myelin oligodendrocyte glycoprotein MOG, which is a known MS auto-antigen, thus explaining its diagnostic activity. Our study offers new molecular bases to design more effective biomarkers and provides a most valid protocol to investigate other systems where the environment effect is determinant for the biological activity.

Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy.

PubMed

Nørgaard, Sisse A; Sand, Fredrik W; Sørensen, Dorte B; Abelson, Klas Sp; Søndergaard, Henrik

2018-01-01

The streptozotocin (STZ)-induced diabetic mouse is a widely used model of diabetes and diabetic nephropathy (DN). However, it is a well-known issue that this model is challenged by high weight loss, which despite supportive measures often results in high euthanization rates. To overcome these issues, we hypothesized that supplementing STZ-induced diabetic mice with water-softened chow in addition to normal chow would reduce weight loss, lower the need for supportive treatment, and reduce the number of mice reaching the humane endpoint of 20% weight loss. In a 15 week STZ-induced DN study we demonstrated that diabetic male mice receiving softened chow had reduced acute weight loss following STZ treatment ( p = 0.045) and additionally fewer mice were euthanized due to weight loss. By supplementing the diabetic mice with softened chow, no mice reached 20% weight loss whereas 37.5% of the mice without this supplement reached this humane endpoint ( p = 0.0027). Excretion of corticosterone metabolites in faeces was reduced in diabetic mice on softened chow ( p = 0.0007), suggesting lower levels of general stress. Finally, it was demonstrated that the water-softened chow supplement did not significantly affect the induction of key disease parameters, i.e. %HbA1C and albuminuria nor result in abnormal teeth wear. In conclusion, supplementation of softened food is refining the STZ-induced diabetic mouse model significantly by reducing stress, weight loss and the number of animals sacrificed due to humane endpoints, while maintaining the key phenotypes of diabetes and nephropathy.

Postnatal Weight Gain Modifies Severity and Functional Outcome of Oxygen-Induced Proliferative Retinopathy

PubMed Central

Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R.; Krah, Nathan M.; Dennison, Roberta J.; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D.; Smith, Lois E.H.

2010-01-01

In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r2 = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome. PMID:21056995

Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy.

PubMed

Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R; Krah, Nathan M; Dennison, Roberta J; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D; Smith, Lois E H

2010-12-01

In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.

Knowing prior methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization status increases the empirical use of glycopeptides in MRSA bacteraemia and may decrease mortality.

PubMed

Robinson, J O; Phillips, M; Christiansen, K J; Pearson, J C; Coombs, G W; Murray, R J

2014-06-01

To compare the management and outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in patients known to be MRSA-colonized/infected (C-patients) with the management and outcome in those not known to be colonized/infected (NC-patients), we conducted a 10-year retrospective review of MRSA bacteraemia in an adult tertiary hospital. Clinical data were obtained by chart review, and mortality data from linked databases. Prior MRSA colonization/infection status was available to treating clinicians at the time of the bacteraemia as a 'Micro-Alert' tag on the patient's labels, in medical charts, and in electronic information systems. C-patients accounted for 35.4% of all MRSA bacteraemia episodes. C-patients were more likely to be indigenous, to be diabetic, or to have a history of previous S. aureus infection. Markers of illness severity (Simplified Acute Physiology Score (SAPS)-II, need for admission to the intensive-care unit, length of stay, and metastatic seeding) were similar in both groups. Empirical therapy included a glycopeptide in 49.3% of C-patients vs. 18.9% of NC-patients (p <0.01), and contained an antibiotic to which the MRSA isolate tested susceptible in vitro in 56.7% of C-patients vs. 45.1% of NC-patients (p 0.13). All-cause 7-day and 30-day mortality were 7.5% vs. 18.9% (p 0.04), and 22.4% vs. 31.1% (p 0.20), in the C-patient and NC-patient groups, respectively. Knowing MRSA colonization status was significantly associated with lower 30-day mortality in Cox regression analysis (p <0.01). These data suggest that mortality from MRSA bacteraemia is lower in C-patients, which may reflect the earlier use of glycopeptides. The low use of empirical glycopeptides in septic patients known to be previously MRSA-colonized/infected may represent a missed opportunity for infection control to positively impact on clinical management. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and

High-performance liquid chromatographic enantioseparation of 2-aminomono- and dihydroxycyclopentanecarboxylic and 2-aminodihydroxycyclohexanecarboxylic acids on macrocyclic glycopeptide-based phases.

PubMed

Berkecz, Róbert; Ilisz, István; Benedek, Gabriella; Fülöp, Ferenc; Armstrong, Daniel W; Péter, Antal

2009-02-06

The direct separation of the enantiomers of four 2-aminomono- or dihydroxycyclopentanecarboxylic acids and four 2-aminodihydroxycyclohexanecarboxylic acids was performed on chiral stationary phases containing macrocyclic glycopeptide antibiotics such as teicoplanin (Astec Chirobiotic T and T2), teicoplanin aglycone (Chirobiotic TAG) or ristocetin A (Chirobiotic R) as chiral selectors. The effects of the nature of organic modifiers, the pH, the mobile phase composition and the structures of the analytes on the separation were investigated. Chirobiotic TAG, and in some cases Chirobiotic T, proved to be the most useful of these columns. The elution sequence was determined in most cases.

Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

PubMed

Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

2016-09-01

Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Propolis prevents diet-induced hyperlipidemia and mitigates weight gain in diet-induced obesity in mice.

PubMed

Koya-Miyata, Satomi; Arai, Norie; Mizote, Akiko; Taniguchi, Yoshifumi; Ushio, Shimpei; Iwaki, Kanso; Fukuda, Shigeharu

2009-12-01

We examined the hypolipidemic effect of propolis in a mouse obesity model induced by a high fat-diet. C57BL/6N mice were fed a high-fat diet ad libitum and given propolis extract intragastrically at 0 mg/kg (control), 5 mg/kg or 50 mg/kg twice daily for 10 d. Compared with mice in the control group, mice in the propolis extract-administrated groups displayed a reduction in all of the following parameters: body weight gain, weight of visceral adipose tissue, liver and serum triglycerides, cholesterol, and non-esterified fatty acids. Real-time polymerase chain reaction analysis of the liver showed down-regulation of mRNA expression associated with fatty acid biosynthesis, including fatty acid synthase, acetyl-CoA carboxylase alpha, and sterol regulatory element binding protein in the propolis-administrated mice. Subsequently, obese C57BL/6N mice that had been administered a high-fat diet were given propolis extract at 0 mg/kg (control), 2.5 mg/kg or 25 mg/kg for 4 weeks. The propolis extract treated mice showed a decrease in weight gain, a reduction of serum non-esterified fatty acids, and lipid accumulation in the liver. These results suggest that propolis extract prevented and mitigated high-fat diet-induced hyperlipidemia by down-regulating the expression of genes associated with lipid metabolism.

Retinopathy of prematurity-induced blindness: birth weight-specific survival and the new epidemic.

PubMed

Gibson, D L; Sheps, S B; Uh, S H; Schechter, M T; McCormick, A Q

1990-09-01

A recent population-based study in the Canadian province of British Columbia showed that, since the mid-1960s, there has been a significant increase in the incidence of retinopathy of prematurity-induced blindness in infants weighing 750 to 999 g at birth. To determine the impact of changing birth weight-specific survival on this new epidemic, all infants born in the province in the period 1952 through 1986 and known to the British Columbia Health Surveillance Registry as having retinopathy of prematurity-induced blindness were identified. In addition, the birth registration records for the 1,299 740 infants born in British Columbia in the same period and the death records of the 22,940 British Columbia-born infants who died in the province before the end of their first year of life were linked using a combination of probabilistic and manual record linkage techniques. These linked records and the records from the Health Surveillance Registry were used to calculate birth weight-specific incidence rates of retinopathy of prematurity-induced blindness in liveborn infants and first-year-of-life survivors. The rates, in 5-year intervals, showed that, in both liveborn infants and first-year survivors, the highest birth weight-specific rates occurred during the first epidemic of retinopathy of prematurity, which ended in British Columbia in 1954. Since the mid-to late-1960s, the incidence of retinopathy of prematurity-induced blindness in liveborn infants weighing less than 1000 g increased steadily whereas in infants weighting 1000 to 1499 g, incidence decreased slightly since the original epidemic ended. However, the experience of first-year-of-life survivors is substantially different.(ABSTRACT TRUNCATED AT 250 WORDS)

A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics

PubMed Central

Delgado, Fernanda; Umans, Benjamin D.; Gerding, Matthew A.; Davis, Brigid M.

2016-01-01

Gram-negative bacteria are notoriously resistant to a variety of high-molecular-weight antibiotics due to the limited permeability of their outer membrane (OM). The basis of OM barrier function and the genetic factors required for its maintenance remain incompletely understood. Here, we employed transposon insertion sequencing to identify genes required for Vibrio cholerae resistance to vancomycin and bacitracin, antibiotics that are thought to be too large to efficiently penetrate the OM. The screen yielded several genes whose protein products are predicted to participate in processes important for OM barrier functions and for biofilm formation. In addition, we identified a novel factor, designated vigA (for vancomycin inhibits growth), that has not previously been characterized or linked to outer membrane function. The vigA open reading frame (ORF) codes for an inner membrane protein, and in its absence, cells became highly sensitive to glycopeptide antibiotics (vancomycin and ramoplanin) and bacitracin but not to other large antibiotics or detergents. In contrast to wild-type (WT) cells, the vigA mutant was stained with fluorescent vancomycin. These observations suggest that VigA specifically prevents the periplasmic accumulation of certain large antibiotics without exerting a general role in the maintenance of OM integrity. We also observed marked interspecies variability in the susceptibilities of Gram-negative pathogens to glycopeptides and bacitracin. Collectively, our findings suggest that the OM barrier is not absolute but rather depends on specific OM-antibiotic interactions. PMID:27216069

1D Self-Assembly and Ice Recrystallization Inhibition Activity of Antifreeze Glycopeptide-Functionalized Perylene Bisimides.

PubMed

Adam, Madeleine K; Jarrett-Wilkins, Charles; Beards, Michael; Staykov, Emiliyan; MacFarlane, Liam R; Bell, Toby D M; Matthews, Jacqueline M; Manners, Ian; Faul, Charl F J; Moens, Pierre D J; Ben, Robert N; Wilkinson, Brendan L

2018-06-04

Antifreeze glycoproteins (AFGPs) are polymeric natural products that have drawn considerable interest in diverse research fields owing to their potent ice recrystallization inhibition (IRI) activity. Self-assembled materials have emerged as a promising class of biomimetic ice growth inhibitor, yet the development of AFGP-based supramolecular materials that emulate the aggregative behavior of AFGPs have not yet been reported. This work reports the first example of the 1D self-assembly and IRI activity of AFGP-functionalized perylene bisimides (AFGP-PBIs). Glycopeptide-functionalized PBIs underwent 1D self-assembly in water and showed modest IRI activity, which could be tuned through substitution of the PBI core. This work presents essential proof-of-principle for the development of novel IRIs as potential supramolecular cryoprotectants and glycoprotein mimics. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Beta-glucan-depleted, glycopeptide-rich extracts from Brewer's and Baker's yeast (Saccharomyces cerevisiae) lower interferon-gamma production by stimulated human blood cells in vitro.

PubMed

Williams, Roderick; Dias, Daniel A; Jayasinghe, Nirupama; Roessner, Ute; Bennett, Louise E

2016-04-15

Regulation of the human immune system requires controlled pro- and anti-inflammatory responses for host defence against infection and disease states. Yeasts (Saccharomyces cerevisiae), as used in brewing and baking, are mostly known for ability to stimulate the human immune-system predominantly reflecting the pro-inflammatory cell wall β-glucans. However, in this study, using food-compatible processing methods, glycopeptide-enriched and β-glucan-depleted products were each prepared from Brewer's and Baker's yeasts, which suppressed production of interferon-γ (IFN-γ) in human whole blood cell assay, signifying that anti-inflammatory factors are also present in yeast. Anti-inflammatory bioactivities of products prepared from Brewer's and Baker's yeast were compared with the commercial yeast product, Epicor®. While unfractionated Epicor was inactive, the C18 resin-binding fractions of Brewer's and Baker's yeast products and Epicor dose-dependently lowered IFN-γ, demonstrating that Epicor also contained both pro-inflammatory (β-glucans) and anti-inflammatory components. Anti-inflammatory activity was attributed to C18 resin-binding species glyco-peptides in Epicor and experimental yeast products. This study demonstrated that pro- and anti-inflammatory factors could be resolved and enriched in yeasts by suitable processing, with potential to improve specific activities. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report.

PubMed

Okazaki, Kosuke; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2017-01-01

Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases. We treated a case of olanzapine-induced weight gain in a 41-year-old man with schizophrenia by switching his medication from olanzapine to asenapine. The weight gain improved after switching the medication, from 80.3 to 75.0 kg, a weight loss of 6.6%, and there was no significant worsening of psychological symptoms or other adverse effects. Asenapine might be effective for treating patients with schizophrenia who experience olanzapine-induced weight gain.

Alterations to Melanocortinergic, GABAergic and Cannabinoid Neurotransmission Associated with Olanzapine-Induced Weight Gain

PubMed Central

Weston-Green, Katrina; Huang, Xu-Feng; Deng, Chao

2012-01-01

Background/Aim Second generation antipsychotics (SGAs) are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. Methodology/Results Levels of pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and glutamic acid decarboxylase (GAD65, enzyme for GABA synthesis) mRNA expression, and cannabinoid CB1 receptor (CB1R) binding density (using [3H]SR-141716A) were examined in the arcuate nucleus (Arc) and dorsal vagal complex (DVC) of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days). Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. Conclusions Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug. PMID:22438946

Weight loss induced by bariatric surgery restores adipose tissue PNPLA3 expression.

PubMed

Wieser, Verena; Adolph, Timon E; Enrich, Barbara; Moser, Patrizia; Moschen, Alexander R; Tilg, Herbert

2017-02-01

Obesity and its related co-morbidities such as non-alcoholic fatty liver disease (NAFLD) are increasing dramatically worldwide. The genetic variation in Patatin-like phospholipase domain-containing protein 3 (PNPLA3), which is also called adiponutrin (ADPN), in residue 148 (I148M, rs738409) has been associated with NAFLD. However, the regulation and function of PNPLA3 in metabolic diseases remains unclear. Laparoscopic gastric banding (LAGB) of severely obese patients reduces body weight, liver and adipose tissue inflammation. In this study, we investigated whether weight loss induced by LAGB affected PNPLA3 expression in hepatic and adipose tissue. Liver and subcutaneous adipose tissue samples were collected from 28 severely obese patients before and 6 months after LAGB. PNPLA3 expression was assessed by quantitative real-time PCR. To understand whether inflammatory stimuli regulated PNPLA3 expression, we studied the effect of tumour necrosis factor alpha (TNFα) and lipopolysaccharide (LPS) on PNPLA3 expression in human adipocytes and hepatocytes. PNPLA3 was strongly expressed in the liver and clearly detectable in subcutaneous adipose tissue of obese patients. Weight loss induced by LAGB of severely obese patients led to significantly increased adipose, but not hepatic, tissue expression of PNPLA3. Subcutaneous PNPLA3 expression negatively correlated with body-mass-index, fasting glucose and fasting insulin. TNFα potently suppressed PNPLA3 expression in adipocytes but not hepatocytes. Weight loss induced by LAGB restored adipose tissue PNPLA3 expression which is suppressed by TNFα. Further studies will be required to determine the functional impact of PNPLA3 and its related genetic variation on adipose tissue inflammation and NAFLD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-cooperative ligand binding and dimerisation in the glycopeptide antibiotic dalbavancin† †Electronic supplementary information (ESI) available. See DOI: 10.1039/C3OB42428F Click here for additional data file.

PubMed Central

Cheng, Mu; Ziora, Zyta M.; Hansford, Karl A.; Blaskovich, Mark A.; Butler, Mark S.

2014-01-01

Dalbavancin, a semi-synthetic glycopeptide with enhanced antibiotic activity compared to vancomycin and teicoplanin, binds to the C-terminal lysyl-d-alanyl-d-alanine subunit of Lipid II, inhibiting peptidoglycan biosynthesis. In this study, micro-calorimetry and electrospray ionization (ESI)-MS have been used to investigate the relationship between oligomerisation of dalbavancin and binding of a Lipid II peptide mimic, diacetyl-Lys-d-Ala-d-Ala (Ac2-Kaa). Dalbavancin dimerised strongly in an anti-cooperative manner with ligand-binding, as was the case for ristocetin A, but not for vancomycin and teicoplanin. Dalbavancin and ristocetin A both adopt an ‘closed’ conformation upon ligand binding, suggesting anti-cooperative dimerisation with ligand-binding may be a general feature of dalbavancin/ristocetin A-like glycopeptides. Understanding these effects may provide insight into design of novel dalbavancin derivatives with cooperative ligand-binding and dimerisation characteristics that could enhance antibiotic activity. PMID:24608916

Effect of gonadectomy on AgRP-induced weight gain in rats.

PubMed

Goodin, Sean Z; Kiechler, Alicia R; Keichler, Alicia R; Smith, Marissa; Wendt, Donna; Strader, April D

2008-12-01

Agouti-related peptide (AgRP), the endogenous antagonist to the melanocortin 3 and 4 receptors, elicits robust hyperphagia and weight gain in rodents when administered directly into the central nervous system. The relative influence of AgRP to cause weight gain in rodents partially depends on the activity level of the melanocortin agonist-producing proopiomelanocortin neurons. Both proopiomelanocortin and AgRP neurons within the arcuate nucleus receive energy storage information from circulating peripheral signals such as leptin and insulin. Another modulator of AgRP activity includes the cell surface molecule syndecan-3. Because leptin and insulin affect food intake in a sexually dimorphic way in rodents and syndecan-3-deficient mice regulate adiposity levels through distinct physiological mechanisms, we hypothesized that AgRP-induced weight gain would also be sexually dimorphic in rats. In the present study, the behavioral and physiological effects of centrally-administered AgRP in male and female were investigated. In male rats, AgRP (1 nmol) induced 5 days (P < 0.0001) of significantly elevated feeding compared with vehicle-treated controls, while females displayed 3 days of hyperphagia (P < 0.05). However, 1 wk after the injection, both male and female rats gained the same percent body weight (6%). Interestingly, female rats exhibited a greater reduction in energy expenditure (Vo2) following AgRP compared with male rats (P < 0.05). Removal of the gonads did not alter cumulative food intake in male or female rats but did attenuate the dramatic reduction in Vo2 exhibited by females. Both intact and gonadectomized rats demonstrated significantly increased respiratory quotient supporting the anabolic action of AgRP (P < 0.01). These findings are novel in that they reveal sex-specific underlying physiology used to achieve weight gain following central AgRP in rats.

The defence of body weight: a physiological basis for weight regain after weight loss.

PubMed

Sumithran, Priya; Proietto, Joseph

2013-02-01

Although weight loss can usually be achieved by restricting food intake, the majority of dieters regain weight over the long-term. In the hypothalamus, hormonal signals from the gastrointestinal tract, adipose tissue and other peripheral sites are integrated to influence appetite and energy expenditure. Diet-induced weight loss is accompanied by several physiological changes which encourage weight regain, including alterations in energy expenditure, substrate metabolism and hormone pathways involved in appetite regulation, many of which persist beyond the initial weight loss period. Safe effective long-term strategies to overcome these physiological changes are needed to help facilitate maintenance of weight loss. The present review, which focuses on data from human studies, begins with an outline of body weight regulation to provide the context for the subsequent discussion of short- and long-term physiological changes which accompany diet-induced weight loss.

The adjunctive use of metformin to treat or prevent atypical antipsychotic-induced weight gain: a review.

PubMed

Khan, Ahsan Y; Macaluso, Matthew; McHale, Robert J; Dahmen, Megan M; Girrens, Kathrine; Ali, Faryal

2010-09-01

Patients with schizophrenia have a greater incidence of being overweight or obese compared with the general population. Such individuals are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidemia, and other metabolic derangements. As a result, frequent monitoring of weight and other metabolic parameters is recommended. In addition, several pharmacologic strategies to help prevent or reduce SGA-induced weight gain have been proposed. Despite this, clinicians often struggle to manage obesity and metabolic issues in such patients. Metformin has attracted attention as a potential treatment option because it is thought to result in weight reduction and improved glycemic control in obese patients with and without type 2 diabetes mellitus. This article focuses on relevant pharmacologic aspects of metformin and reviews currently available evidence on the use of metformin as an augmentation agent for the treatment or prevention of SGA-induced weight gain.

Herpes virus entry mediator signaling in the brain is imperative in acute inflammation-induced anorexia and body weight loss.

PubMed

Kim, Kwang Kon; Jin, Sung Ho; Lee, Byung Ju

2013-09-01

Reduced appetite and body weight loss are typical symptoms of inflammatory diseases. A number of inflammatory stimuli are responsible for the imbalance in energy homeostasis, leading to metabolic disorders. The herpes virus entry mediator (HVEM) protein plays an important role in the development of various inflammatory diseases, such as intestinal inflammation and diet-induced obesity. However, the role of HVEM in the brain is largely unknown. This study aims to investigate whether HVEM signaling in the brain is involved in inflammation-induced anorexia and body weight loss. Food intake and body weight were measured at 24 hours after intraperitoneal injection of lipopolysaccharide (LPS) or intracerebroventricular injection of recombinant mouse LIGHT (also called tumor necrosis factor receptor superfamily 14, TNFSF14), an HVEM ligand, into 8- to 10-week-old male C57BL/6 mice and mice lacking HVEM expression (HVEM-/-). We also assessed LPS-induced change in hypothalamic expression of HVEM using immunohistochemistry. Administration of LPS significantly reduced food intake and body weight, and moreover, increased expression of HVEM in the hypothalamic arcuate nucleus. However, LPS induced only minor decreases in food intake and body weight in HVEM-/- mice. Administration of LIGHT into the brain was very effective at decreasing food intake and body weight in wild-type mice, but was less effective in HVEM-/- mice. Activation of brain HVEM signaling is responsible for inflammation-induced anorexia and body weight loss.

Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation.

PubMed Central

Calvete, J J; Rivas, G; Maruri, M; Alvarez, M V; McGregor, J L; Hew, C L; Gonzalez-Rodriguez, J

1988-01-01

Early digestion of pure human platelet glycoprotein IIIa (GPIIIa) leads to a single cleavage of the molecule at 23 kDa far from one of the terminal amino acids. Automated Edman degradation demonstrates that GPIIIa and the smaller (23 kDa) tryptic fragment share the same N-terminal amino acid sequence. A further cleavage occurs in the larger fragment (80 kDa), reducing its apparent molecular mass by 10 kDa. The 23 kDa fragment remains attached to the larger ones in unreduced samples. Stepwise reduction of early digested GPIIIa with dithioerythritol selectively reduces the single disulphide bond joining the smaller (23 kDa) to the larger (80/70 kDa) fragments. Two fractions were obtained by size-exclusion chromatography of early digested GPIIIa after partial or full reduction and alkylation. The larger-size fraction contains the 80/70 kDa fragments, while the 23 kDa fragment is isolated in the smaller. The amino acid compositions of these fractions do not differ very significantly from the composition of GPIIIa; however the 23 kDa fragment contains only 10.2% by weight of sugars and is richer in neuraminic acid. Disulphide bonds are distributed four in the 23 kDa glycopeptide and 20-21 in the 80/70 kDa glycopeptide. The epitope for P37, a monoclonal antibody which inhibits platelet aggregation [Melero & González-Rodríguez (1984) Eur. J. Biochem. 141, 421-427] is situated within the first 17 kDa of the N-terminal region of GPIIIa, which gives a special functional interest to this extracellular region of GPIIIa. On the other hand, the epitopes for GPIIIa-specific monoclonal antibodies, P6, P35, P40 and P97, which do not interfere with platelet aggregation, are located within the larger tryptic fragment (80/70 kDa). Thus, the antigenic areas available in the extracellular surface of GPIIIa for these five monoclonal antibodies are now more precisely delineated. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2455507

Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats

PubMed Central

Fisas, Angels; Codony, Xavier; Romero, Gonzalo; Dordal, Alberto; Giraldo, Jesus; Mercé, Ramon; Holenz, Jörg; Heal, David; Buschmann, Helmut; Pauwels, Petrus Johan

2006-01-01

E-6837 is a novel, selective and high-affinity 5-HT6 receptor ligand (pKi: 9.13) which in vitro demonstrates partial agonism at a presumably silent rat 5-HT6 receptor and full agonism at a constitutively active human 5-HT6 receptor by monitoring the cAMP signaling pathway. The effects of chronic treatment with E-6837 were determined in diet-induced obese (DIO)-rats on changes in body weight, food and water intake, plasma indices of comorbid risk factors, and weight regain on compound withdrawal. The centrally acting antiobesity drug, sibutramine, was used as the reference comparator. Sustained body weight loss and decreased cumulative food intake of DIO-rats was observed with E-6837 (30 mg kg−1, p.o., twice a day) during the 4-week treatment period. The onset of the E-6837 effect on body weight was slower than that of sibutramine (5 mg kg−1, p.o.), while its maximal effect was greater, that is −15.7 versus −11.0%. E-6837-induced weight loss was exclusively mediated by a decrease (31.7%) in fat mass, with a concomitant reduction (49.6%) in plasma leptin. Reduced obesity was also reflected in improved glycemic control. Although weight regain occurred after withdrawal from either compound, the body weights after E-6837 (−6.6%) remained lower than after sibutramine (−3.8%) indicating that the greater efficacy of the former did not result in profound rebound hyperphagia/weight gain. These results show that the 5-HT6 receptor partial agonist, E-6837, is a promising new approach to the management of obesity with the potential to produce greater sustained weight loss than sibutramine. PMID:16783408

Prior exercise training blunts short-term high-fat diet-induced weight gain.

PubMed

Snook, Laelie A; MacPherson, Rebecca E K; Monaco, Cynthia M F; Frendo-Cumbo, Scott; Castellani, Laura; Peppler, Willem T; Anderson, Zachary G; Buzelle, Samyra L; LeBlanc, Paul J; Holloway, Graham P; Wright, David C

2016-08-01

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet. Copyright © 2016 the American Physiological Society.

Effect of diet-induced weight loss on inflammatory cytokines in obese women.

PubMed

Tajik, N; Keshavarz, S A; Masoudkabir, F; Djalali, M; Sadrzadeh-Yeganeh, H Hale; Eshraghian, M R; Chamary, M; Ahmadivand, Z; Yazdani, T; Javanbakht, M H

2013-04-01

Obesity is associated with lowgrade systemic inflammation which has been linked to the increased risk of cardiovascular disease and Type 2 diabetes in obese patients. To evaluate changes in pro/anti-inflammatory adipocytokines and metabolic profile after moderate diet-induced weight loss. Twenty-nine pre-menopausal obese women (body mass index ≥30 kg/m2) aged 21 to 54 years without diabetes, hypertension, or hyperlipidemia, were enrolled in this study. We measured anthropometric parameters, lipid and glucose profiles, interleukin (IL)-6, IL-10, and IL-18 in obese women, who then entered a medically supervised program aimed at reducing body weight by 10% or more. Obese women restricted their caloric intake (by 500-1000 kcal/day) and consumed 50 g/day of a fiber supplement (Slim Last Powder) for 12 weeks. By completing the dietary intervention program, weight (Δ = -10.0%, p<0.0001), body mass index, waist circumference, triceps skinfold thickness, total cholesterol, triglyceride, and fasting plasma glucose significantly decreased, while HDL-cholesterol significantly increased. While plasma levels of IL-6 and IL-18 decreased by 27% after 12 weeks, no significant change was observed in circulating levels of IL-10. Our study suggests that an improved body composition induced by restriction of energy intake is associated with favorable serum concentrations of IL-6 and IL-18 in obese women. However, the anti-inflammatory IL-10 is not affected by a moderate weight decrease.

Topiramate-induced weight loss in schizophrenia: a retrospective case series study.

PubMed

Lévy, Emmanuel; Agbokou, Catherine; Ferreri, Florian; Chouinard, Guy; Margolese, Howard C

2007-01-01

Atypical antipsychotics have been associated with weight gain. This study examines the efficacy of adjunctive topiramate in patients with schizophrenia and schizoaffective disorder with antipsychotic-induced weight gain. A 2-year retrospective case analysis was performed in all 300 patients of the outpatient Special Follow-up Clinic for chronic schizophrenia and related psychoses at the Allan Memorial Institute, McGill University Health Centre (Montreal, Canada), a tertiary care University teaching hospital. 10 patients met study inclusion criteria. Mean daily topiramate dose was 197.5 mg (A+/-77) (range, 125-400 mg). Topiramate produced continued weight loss throughout the study duration without tolerance. Patients treated for 6 months and more had significantly higher Body Mass Index (BMI) differences than those treated for shorter durations (BMI-d6 months=-4.7A+/-2.4; BMI-d2 months=-3.2A+/-2.3; P=0.015). BMI changes were similar across genders. This study supports topiramate use to target weight loss in stable overweight schizophrenic patients as a potential therapy that requires further investigation.

Effect of CMC Molecular Weight on Acid-Induced Gelation of Heated WPI-CMC Soluble Complex.

PubMed

Huan, Yan; Zhang, Sha; Vardhanabhuti, Bongkosh

2016-02-01

Acid-induced gelation properties of heated whey protein isolate (WPI) and carboxymethylcellulose (CMC) soluble complex were investigated as a function of CMC molecular weight (270, 680, and 750 kDa) and concentrations (0% to 0.125%). Heated WPI-CMC soluble complex with 6% protein was made by heating biopolymers together at pH 7.0 and 85 °C for 30 min and diluted to 5% protein before acid-induced gelation. Acid-induced gel formed from heated WPI-CMC complexes exhibited increased hardness and decreased water holding capacity with increasing CMC concentrations but gel strength decreased at higher CMC content. The highest gel strength was observed with CMC 750 k at 0.05%. Gels with low CMC concentration showed homogenous microstructure which was independent of CMC molecular weight, while increasing CMC concentration led to microphase separation with higher CMC molecular weight showing more extensive phase separation. When heated WPI-CMC complexes were prepared at 9% protein the acid gels showed improved gel hardness and water holding capacity, which was supported by the more interconnected protein network with less porosity when compared to complexes heated at 6% protein. It is concluded that protein concentration and biopolymer ratio during complex formation are the major factors affecting gel properties while the effect of CMC molecular weight was less significant. © 2016 Institute of Food Technologists®

Examination of mechanisms (E-MECHANIC) of exercise-induced weight compensation: study protocol for a randomized controlled trial.

PubMed

Myers, Candice A; Johnson, William D; Earnest, Conrad P; Rood, Jennifer C; Tudor-Locke, Catrine; Johannsen, Neil M; Cocreham, Shannon; Harris, Melissa; Church, Timothy S; Martin, Corby K

2014-06-07

Weight loss induced only by exercise is frequently less than expected, possibly because of compensatory changes in energy intake and/or energy expenditure. The purpose of the Examination of Mechanisms (E-MECHANIC) of Exercise-Induced Weight Compensation trial is to examine whether increased energy intake and/or reduced spontaneous activity or energy expenditure (outside of structured exercise) account for the less than expected, exercise-associated weight loss. E-MECHANIC is a three-arm, 6-month randomized (1:1:1) controlled trial. The two intervention arms are exercise doses that reflect current recommendations for (1) general health (8 kcal/kg body weight per week (8 KKW), about 900 kcal/wk) and (2) weight loss (20 KKW, about 2,250 kcal/wk). The third arm, a nonexercise control group, will receive health information only. The sample will include a combined total of 198sedentary, overweight or obese (body mass index: ≥25 kg/m² to ≤45 kg/m²) men and women ages 18 to 65 years. The exercise dose will be supervised and tightly controlled in an exercise training laboratory. The primary outcome variables are energy intake, which will be measured using doubly labeled water (adjusted for change in energy stores) and laboratory-based food intake tests, and the discrepancy between expected weight loss and observed weight loss. Secondary outcomes include changes in resting metabolic rate (adjusted for change in body mass), activity levels (excluding structured exercise) and body composition. In an effort to guide the development of future interventions, the participants will be behaviorally phenotyped and defined as those who do compensate (that is, fail to lose the amount of weight expected) or do not compensate (that is, lose the amount of weight expected or more). In this study, we will attempt to identify underlying mechanisms to explain why exercise elicits less weight loss than expected. This information will guide the development of interventions to increase

Antibody induction directed against the tumor-associated MUC4 glycoprotein.

PubMed

Cai, Hui; Palitzsch, Björn; Hartmann, Sebastian; Stergiou, Natascha; Kunz, Horst; Schmitt, Edgar; Westerlind, Ulrika

2015-04-13

Mucin glycoproteins are important diagnostic and therapeutic targets for cancer treatment. Although several strategies have been developed to explore anti-tumor vaccines based on MUC1 glycopeptides, only few studies have focused on vaccines directed against the tumor-associated MUC4 glycoprotein. MUC4 is an important tumor marker overexpressed in lung cancer and uniquely expressed in pancreatic ductual adenocarcinoma. The aberrant glycosylation of MUC4 in tumor cells results in an exposure of its peptide backbone and the formation of tumor-associated glycopeptide antigens. Due to the low immunogenicity of these endogenous structures, their conjugation with immune stimulating peptide or protein carriers are required. In this study, MUC4 tandem-repeat glycopeptides were conjugated to the tetanus toxoid and used for vaccination of mice. Immunological evaluations showed that our MUC4-based vaccines induced very strong antigen-specific immune responses. In addition, antibody binding epitope analysis on glycopeptide microarrays, were demonstrating a clear glycosylation site dependence of the induced antibodies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acidosis and weight loss are induced by cyclosporin A in uninephrectomized rats.

PubMed

Jaramillo-Juárez, F; Rodríguez-Vázquez, M L; Namorado, M C; Martín, D; Reyes, J L

2000-02-01

The effects of cyclosporin A (CyA, 50 mg/kg body weight) or its commercial vehicle (cremophor) on the acid-base regulation of uninephrectomized rats were assessed for 7 days and in non-nephrectomized rats for 15 days. CyA induced a marked systemic acidosis, accompanied by decreases in blood PCO(2) and plasma bicarbonate. Untreated uninephrectomized rats did not show the acidosis. In CyA-treated rats the urine pH decreased (control 6. 65+/-0.06 vs. CyA 6.18+/-0.08; P<0.01) as well as urinary bicarbonate (non-nephrectomized rats 7.50+/-1.88 mM vs. uninephrectomy plus CyA 0.75+/- 0.06 mM; P<0.01), suggesting partial renal compensation of systemic acidosis. Titratable acidity increased in CyA-treated rats (control 21.6+/-1.2 vs. CyA 63.3+/-12.0 microEq/l; P<0.001). Phosphate, glucose, and osmolar clearances were not significantly altered in non-nephrectomized rats treated with CyA for 15 days. There was a striking decrease in body weight in CyA-treated rats (control 274.0+/-3.8 vs. CyA 225.0+/-5.1 g; P<0. 01), but compensatory growth of the remaining kidney was not prevented by this drug or by its vehicle. In summary, CyA induced a severe metabolic acidosis in uninephrectomized rats that was not compensated by the remaining kidney, in spite of the well-preserved compensatory weight gain of this organ. Loss of body weight was significant in CyA-treated animals.

High molecular weight hyaluronan decreases oxidative DNA damage induced by EDTA in human corneal epithelial cells

PubMed Central

Ye, J; Wu, H; Wu, Y; Wang, C; Zhang, H; Shi, X; Yang, J

2012-01-01

Purpose To investigate the toxic effects of ethylenediaminetetraacetic acid disodium salt (EDTA), a corneal penetration enhancer in topical ophthalmic formulations, on DNA in human corneal epithelial cells (HCEs), and to investigate whether the effect induced by EDTA can be inhibited by high molecular weight hyaluronan (HA). Methods Cells were exposed to EDTA in concentrations ranging from 0.00001 to 0.01% for 60 min, or 30 min high molecular weight HA pretreatment followed by EDTA treatment. The cell viability was measured by the MTT test. Cell apoptosis was determined with annexin V staining by flow cytometry. The DNA single- and double-strand breaks of HCEs were examined by alkaline comet assay and by immunofluorescence microscope detection of the phosphorylated form of histone variant H2AX (γH2AX) foci, respectively. Reactive oxygen species (ROS) production was assessed by the fluorescent probe, 2′, 7′-dichlorodihydrofluorescein diacetate. Results EDTA exhibited no adverse effect on cell viability and did not induce cell apoptosis in human corneal epithelial cells at concentrations lower than 0.01%. However, a significant increase of DNA single- and double-strand breaks was observed in a dose-dependent manner with all the concentrations of EDTA tested in HCEs. In addition, EDTA treatment led to elevated ROS generation. Moreover, 30 min preincubation with high molecular weight HA significantly decreased EDTA-induced ROS generation and DNA damage. Conclusions EDTA could induce DNA damage in HCEs, probably through oxidative stress. Furthermore, high molecular weight HA was an effective protective agent that had antioxidant properties and decreased DNA damage induced by EDTA. PMID:22595911

Diet-induced thermogenesis in postoperatve Roux-en-Y gastric bypass patients with weight regain.

PubMed

Cardeal, Mariane de Almeida; Faria, Silvia Leite; Faria, Orlando Pereira; Facundes, Marcela; Ito, Marina Kiyomi

2016-06-01

Bariatric surgery has been shown to be an effective treatment for obesity. Changes in energy expenditure, especially through diet-induced thermogenesis (DIT), have been identified as one of the mechanisms to explain this success. However, not all patients are able to maintain healthy postoperative weight loss. Therefore, a question arises: In the weight regain after bariatric surgery, are these changes in energy metabolism still active? To investigate if weight regain after Roux-en-Y gastric bypass (RYGB) surgery is associated with a lower diet-induced thermogenesis in the late postoperative period. A cross-sectional study with the participants chosen from among the patients from a private practice. This was a cross-sectional study where 3 groups of female patients were evaluated: (1) 20 patients with a RYGB postoperative time period of at least 2 years, who kept a healthy weight after surgery (loss of at least 50% of excess weight; Healthy group); (2) 19 patients with clinically severe obesity (BMI>40 kg/m(2), without co-morbidities and>35 kg/m(2), with co-morbidities; Pre group); (3) 18 patients who experienced weight regain after RYGB (Regain group). The 3 groups were submitted to indirect calorimetry to measure resting metabolic rate (RMR), respiratory quotient (RQ), and DIT. Immediately after the RMR measurement, a mixed meal of regular consistency was offered. Ten minutes after the food intake began, energy expenditure measurements were initiated continuing throughout the following 3 postprandial hours. Body composition was evaluated using multifrequency bioelectrical impedance. In subgroups of the studied population, glucose and insulin levels were measured at baseline and at 30, 60, 90, 120, and 180 minutes after feeding. The mean area under the curve (AUC) between the 3 groups and measurements at baseline were compared using the analysis of variance (ANOVA). The Healthy group had the highest weight adjusted RMR value compared with both the Pre and Regain

Mechanisms of Weight Regain following Weight Loss.

PubMed

Blomain, Erik Scott; Dirhan, Dara Anne; Valentino, Michael Anthony; Kim, Gilbert Won; Waldman, Scott Arthur

2013-01-01

Obesity is a world-wide pandemic and its incidence is on the rise along with associated comorbidities. Currently, there are few effective therapies to combat obesity. The use of lifestyle modification therapy, namely, improvements in diet and exercise, is preferable over bariatric surgery or pharmacotherapy due to surgical risks and issues with drug efficacy and safety. Although they are initially successful in producing weight loss, such lifestyle intervention strategies are generally unsuccessful in achieving long-term weight maintenance, with the vast majority of obese patients regaining their lost weight during followup. Recently, various compensatory mechanisms have been elucidated by which the body may oppose new weight loss, and this compensation may result in weight regain back to the obese baseline. The present review summarizes the available evidence on these compensatory mechanisms, with a focus on weight loss-induced changes in energy expenditure, neuroendocrine pathways, nutrient metabolism, and gut physiology. These findings have added a major focus to the field of antiobesity research. In addition to investigating pathways that induce weight loss, the present work also focuses on pathways that may instead prevent weight regain. Such strategies will be necessary for improving long-term weight loss maintenance and outcomes for patients who struggle with obesity.

Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation.

PubMed

Fernø, Johan; Varela, Luis; Skrede, Silje; Vázquez, María Jesús; Nogueiras, Rubén; Diéguez, Carlos; Vidal-Puig, Antonio; Steen, Vidar M; López, Miguel

2011-01-01

The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance.

Olanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylation

PubMed Central

Fernø, Johan; Vázquez, María Jesús; Nogueiras, Rubén; Diéguez, Carlos; Vidal-Puig, Antonio; Steen, Vidar M.; López, Miguel

2011-01-01

The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance. PMID:21695181

Hypothalamic histamine H1 receptor-AMPK signaling time-dependently mediates olanzapine-induced hyperphagia and weight gain in female rats.

PubMed

He, Meng; Zhang, Qingsheng; Deng, Chao; Wang, Hongqin; Lian, Jiamei; Huang, Xu-Feng

2014-04-01

Although second-generation antipsychotics induce severe weight gain and obesity, there is a lack of detailed knowledge about the progressive development of antipsychotic-induced obesity. This study examined the hypothalamic histamine H1 receptor and AMP-activated protein kinase (H1R-AMPK) signaling at three distinctive stages of olanzapine-induced weight gain (day 1-12: early acceleration, day 13-28: middle new equilibrium, and day 29-36: late heavy weight maintenance). At the early acceleration stage, the rats were hyperphagic with an underlying mechanism of olanzapine-increased H1R mRNA expression and AMPK phosphorylation (pAMPK), in which pAMPK levels positively correlated with H1R mRNA expression and food intake. At the middle stage, when the rats were no longer hyperphagic, the changes in H1R-AMPK signaling vanished. At the late stage, olanzapine increased H1R mRNA expression but decreased pAMPK which were positively and negatively correlated with weight gain, respectively. These data suggest a time-dependent change of H1R-AMPK signaling, where olanzapine activates AMPK by blocking the H1Rs and causing hyperphagia in the acute phase. The chronic blockade of H1R may contribute to the late stage of olanzapine-induced heavy weight maintenance. However, pAMPK was no longer elevated and actually decreased. This indicates that AMPK acts as an energy sensor and negatively responds to the positive energy balance induced by olanzapine. Furthermore, we showed that an H1R agonist, 2-(3-trifluoromethylphenyl) histamine, can significantly inhibit olanzapine-induced hyperphagia and AMPK activation in the mediobasal hypothalamus in a dose dependent manner. Therefore, lowering H1R-AMPK signaling is an effective treatment for the olanzapine-induced hyperphagia associated with the development of obesity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Decreased plasma levels of ceruloplasmin after diet-induced weight loss in obese women.

PubMed

Tajik, N; Golpaie, A; Keshavarz, S A; Djalali, M; Sehat, M; Masoudkabir, F; Ahmadivand, Z; Fatehi, F; Zare, M; Yazdani, T

2012-06-01

Plasma ceruloplasmin (Cp) has been shown to be a risk factor for cardiovascular disease and also to be associated with obesity. However, it is not known whether weight loss could decrease the plasma Cp levels. To investigate the effect of diet-induced weight loss on plasma Cp in obese women. Sixty-seven healthy obese women [age =33.4±8.7 yr, body mass index (BMI) =36.0±4.8 kg/m2] were entered into a medically supervised program aimed at reducing body weight by 10% or more. Weight loss was achieved through a diet providing a daily energy deficit of 500-1000 kcal/day. In addition, all patients were prescribed to use 50 g of a fiber supplement per day. For all subjects, assessment of dietary intake, anthropometric indices, and plasma levels of C-reactive protein and Cp was performed at the first visit and repeated at 12th week of follow-up. By completing the program, weight (Δ=-9.5%, p<0.0001), BMI (Δ=-9.7%, p<0.0001), waist-circumference (Δ=-6.1%, p<0.0001), and triceps skinfold thickness (Δ=-14.9%, p<0.0001) significantly decreased. Plasma Cp significantly decreased after 12 weeks of dietary intervention (33.6±5.6 mg/dl vs 25.2±5.8 mg/dl, p<0.0001). Percent change in Cp was correlated with percent change in waist-circumference (r=446, p=0.015). Our study suggests that an improved body composition induced by restriction of energy intake is associated with decreased serum concentrations of Cp in obese women which in turn might have reduced the subjects' risk of developing cardiovascular disease.

Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats

PubMed Central

Haver, Alvin; Chelikani, Prasanth K.; Apenteng, Bettye; Perriotte-Olson, Curtis; Anders, Krista; Steenson, Sharalyn; Blevins, James E.

2012-01-01

Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg−1·h−1)] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg−1·h−1) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats. PMID:22510712

Effects of canagliflozin on weight loss in high-fat diet-induced obese mice.

PubMed

Ji, Wenjun; Zhao, Mei; Wang, Meng; Yan, Wenhui; Liu, Yuan; Ren, Shuting; Lu, Jun; Wang, Bing; Chen, Lina

2017-01-01

Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been shown to reduce body weight during the treatment of type 2 diabetes mellitus (T2DM). In this study, we sought to determine the role of canagliflozin in body weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive control. The body weight, liver weight, liver morphology, total cholesterol (TC) and triglyceride (TG) levels were examined. Signaling molecules, including diacylgycero1 acyltransferase-2 (DGAT2), peroxisome proliferation receptor alpha-1 (PPARα1), PPARγ1, PPARγ2 mRNA levels and the protein expression of SGLT2 were evaluated. Canagliflozin reduced body weight, especially the high-dose canagliflozin, and resulted in increased body weight loss compared with orlistat. Moreover, canagliflozin reduced the liver weight and the ratio of liver weight to body weight, lowered the serum levels of TC and TG, and ameliorated liver steatosis. During the canagliflozin treatment, SGLT2, DGAT2, PPARγ1 and PPARγ2 were inhibited, and PPARα1 was elevated in the liver tissues. This finding may explain why body weight was reduced and secondary liver injury was ameliorated in response to canagliflozin. Together, the results suggest that canagliflozin may be a potential anti-obesity strategy.

Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol

PubMed Central

Cluny, Nina L.; Keenan, Catherine M.; Reimer, Raylene A.; Le Foll, Bernard; Sharkey, Keith A.

2015-01-01

Objective Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Methods Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. Results THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Conclusions Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity. PMID:26633823

Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol.

PubMed

Cluny, Nina L; Keenan, Catherine M; Reimer, Raylene A; Le Foll, Bernard; Sharkey, Keith A

2015-01-01

Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.

Epidemiological and molecular characterization of Staphylococcus haemolyticus strains, from a hematology ward, with decreased susceptibility to glycopeptides.

PubMed

Ma, Xiao Xue; Sun, Dan Dan; Hu, Jian; Wang, En Hua; Luo, En Jie

2011-06-01

In the present study, we report on the reduced susceptibility to teicoplanin among clinical isolates of Staphylococcus haemolyticus in a hematology ward of a teaching hospital. The molecular characterization of 17 S. haemolyticus strains was performed using mec gene complex classification, pulsed-field gel electrophoresis analysis, and minimum inhibitory concentration examination. Pulsotype A strains carrying a class C2 mec gene complex were the most prevalent strains, at 64.7%. In vivo selection of stepwise increase in resistance to vancomycin and teicoplanin was observed in three S. haemolyticus strains serially isolated from a case patient. The results of the present study suggest the regional spread of certain S. haemolyticus clones with diminished susceptibility to glycopeptides, emphasizing the need for continuous monitoring of minimum inhibitory concentration levels of vancomycin and teicoplanin in S. haemolyticus strains, and the importance of infection control practices to prevent its transmission.

Theonellamide G, a potent antifungal and cytotoxic bicyclic glycopeptide from the Red Sea marine sponge Theonella swinhoei.

PubMed

Youssef, Diaa T A; Shaala, Lamiaa A; Mohamed, Gamal A; Badr, Jihan M; Bamanie, Faida H; Ibrahim, Sabrin R M

2014-04-01

In our search for bioactive metabolites from marine organisms, we have investigated the polar fraction of the organic extract of the Red Sea sponge Theonella swinhoei. Successive chromatographic separations and final HPLC purification of the potent antifungal fraction afforded a new bicyclic glycopeptide, theonellamide G. The structure of the peptide was determined using extensive 1D and 2D NMR and high-resolution mass spectral determinations. The absolute configuration of theonellamide G was determined by chemical degradation and 2D NMR spectroscopy. Theonellamide G showed potent antifungal activity towards wild and amphotericin B-resistant strains of Candida albicans with IC₅₀ of 4.49 and 2.0 μM, respectively. Additionally, it displayed cytotoxic activity against the human colon adenocarcinoma cell line (HCT-16) with IC₅₀ of 6.0 μM. These findings provide further insight into the chemical diversity and biological activities of this class of compounds.

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats.

PubMed

Foletto, Kelly Carraro; Melo Batista, Bruna Aparecida; Neves, Alice Magagnin; de Matos Feijó, Fernanda; Ballard, Cíntia Reis; Marques Ribeiro, Maria Flávia; Bertoluci, Marcello Casaccia

2016-01-01

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low molecular-weight gel fraction of Aloe vera exhibits gastroprotection by inducing matrix metalloproteinase-9 inhibitory activity in alcohol-induced acute gastric lesion tissues.

PubMed

Park, Chul-Hong; Son, Hyeong-U; Yoo, Chi-Yeol; Lee, Sang-Han

2017-12-01

Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.

Multivalent glycopeptide dendrimers for the targeted delivery of antigens to dendritic cells.

PubMed

García-Vallejo, Juan J; Ambrosini, Martino; Overbeek, Annemieke; van Riel, Wilhelmina E; Bloem, Karien; Unger, Wendy W J; Chiodo, Fabrizio; Bolscher, Jan G; Nazmi, Kamran; Kalay, Hakan; van Kooyk, Yvette

2013-04-01

Dendritic cells are the most powerful type of antigen presenting cells. Current immunotherapies targeting dendritic cells have shown a relative degree of success but still require further improvement. One of the most important issues to solve is the efficiency of antigen delivery to dendritic cells in order to achieve an appropriate uptake, processing, and presentation to Ag-specific T cells. C-type lectins have shown to be ideal receptors for the targeting of antigens to dendritic cells and allow the use of their natural ligands - glycans - instead of antibodies. Amongst them, dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) is an interesting candidate due to its biological properties and the availability of its natural carbohydrate ligands. Using Le(b)-conjugated poly(amido amine) (PAMAM) dendrimers we aimed to characterize the optimal level of multivalency necessary to achieve the desired internalization, lysosomal delivery, Ag-specific T cell proliferation, and cytokine response. Increasing DC-SIGN ligand multivalency directly translated in an enhanced binding, which might also be interesting for blocking purposes. Internalization, routing to lysosomal compartments, antigen presentation and cytokine response could be optimally achieved with glycopeptide dendrimers carrying 16-32 glycan units. This report provides the basis for the design of efficient targeting of peptide antigens for the immunotherapy of cancer, autoimmunity and infectious diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

DRD2 Promoter Region Variation Predicts Antipsychotic-Induced Weight Gain in First Episode Schizophrenia

PubMed Central

Lencz, Todd; Robinson, Delbert G.; Napolitano, Barbara; Sevy, Serge; Kane, John M.; Goldman, David; Malhotra, Anil K.

2010-01-01

Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between −141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone (RIS) vs. olanzapine (OLZ). Carriers of the deletion allele (n=29) were compared to Ins/Ins homozygotes (non-carriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers demonstrated significantly more weight gain after 6 weeks of treatment regardless of assigned medication. While deletion carriers were prescribed higher doses of OLZ (but not RIS), dose did not appear to account for the genotype effects on weight gain. Given previous evidence that deletion carriers demonstrate reduced symptom response to medication, additional study of appropriate treatment options for these patients appears warranted. PMID:20664489

Multi-hormonal weight loss combinations in diet-induced obese rats: therapeutic potential of cholecystokinin?

PubMed

Trevaskis, James L; Turek, Victoria F; Griffin, Peter S; Wittmer, Carrie; Parkes, David G; Roth, Jonathan D

2010-05-11

Cholecystokinin (CCK) acutely synergizes with amylin to suppress food intake in lean mice. To extend on these findings, the present studies sought to identify neural correlates for the interaction of amylin and CCK, as well as further understand the therapeutic potential of CCK-based combinations in obesity. First, c-Fos activation was assessed in various brain nuclei after a single intraperitoneal injection of amylin (5microg/kg) and/or CCK (5microg/kg). Amylin and CCK additively increased c-Fos within the area postrema (AP), predominantly in noradrenergic (e.g., dopamine-beta-hydroxylase-containing) cells. Next, amylin (100 or 300microg/kg/d) and/or CCK (100 or 300microg/kg/d) were subcutaneously infused for 7days in diet-induced obese (DIO) rats. Amylin treatment of DIO rats for 7days induced significant body weight loss. CCK, while ineffective alone, significantly enhanced body weight loss when co-administered with the higher dose of amylin. Finally, the addition of CCK (300microg/kg/d) to leptin (125microg/kg/d), and to the combination of amylin (50microg/kg/d) and leptin (125microg/kg/d), was also explored in DIO rats via sustained subcutaneous infusion for 14days. Infusion of amylin/leptin/CCK for 14days exerted significantly greater body weight loss, inhibition of food intake, and reduction in adiposity compared to amylin/leptin treatment alone in DIO rats. However, co-infusion of CCK and leptin was an ineffective weight loss regimen in this model. Whereas CCK agonism alone is ineffective at eliciting or maintaining weight loss, it durably augmented the food intake and body weight-lowering effects of amylin and amylin/leptin in a relevant disease model, and when combined with amylin, cooperatively activated neurons within the caudal brainstem. Copyright 2010 Elsevier Inc. All rights reserved.

Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease.

PubMed

Teff, Karen L; Rickels, Michael R; Grudziak, Joanna; Fuller, Carissa; Nguyen, Huong-Lan; Rickels, Karl

2013-09-01

Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior.

High-performance liquid chromatographic enantioseparation of monoterpene-based 2-amino carboxylic acids on macrocyclic glycopeptide-based phases.

PubMed

Sipos, László; Ilisz, István; Pataj, Zoltán; Szakonyi, Zsolt; Fülöp, Ferenc; Armstrong, Daniel W; Péter, Antal

2010-10-29

The enantiomers of five monoterpene-based 2-amino carboxylic acids were directly separated on chiral stationary phases containing macrocyclic glycopeptide antibiotics such as teicoplanin (Astec Chirobiotic T and T2) and teicoplanin aglycone (Chirobiotic TAG) as chiral selectors. The effects of pH, the mobile phase composition, the structure of the analyte and temperature on the separations were investigated. Experiments were performed at constant mobile phase compositions in the temperature range 10-40°C to study the effects of temperature and thermodynamic parameters on separations. Apparent thermodynamic parameters and T(iso) values were calculated from plots of ln k or ln α versus 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantioseparations were in most cases enthalpy driven. The sequence of elution of the enantiomers was determined in all cases. Copyright © 2010 Elsevier B.V. All rights reserved.

Frequency weighting for vibration-induced white finger compatible with exposure-response models.

PubMed

Brammer, Anthony J; Pitts, Paul M

2012-01-01

An analysis has been performed to derive a frequency weighting for the development of vibration-induced white finger (VWF). It employs a model to compare health risks for pairs of population groups that are selected to have similar health outcomes from operating power tools or machines with markedly different acceleration spectra (rock drills, chain saws, pavement breakers and motorcycles). The model defines the Relative Risk, RR(f(trial)), which is constructed from the ratio of daily exposures and includes a trial frequency weighting that is applied to the acceleration spectra. The trial frequency weighting consists of a frequency-independent primary frequency range, and subordinate frequency ranges in which the response to vibration diminishes, with cut-off frequencies that are changed to influence the magnitude of RR(f(trial)). The frequency weighting so derived when RR(f(trial)) = 1 is similar to those obtained by other methods (W(hf), W(hT)). It consists of a frequency independent range from about 25 Hz to 500 Hz (-3 dB frequencies), with an amplitude cut-off rate of 12 dB/octave below 25 Hz and above 500 Hz. The range is compatible with studies of vasoconstriction in persons with VWF. The results provide further evidence that the ISO frequency weighting may be inappropriate for assessing the risk of developing VWF.

Preventing Olanzapine-Induced Weight Gain Using Betahistine: A Study in a Rat Model with Chronic Olanzapine Treatment

PubMed Central

Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

2014-01-01

Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (−45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (−51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment. PMID:25084453

Changes in Leptin Signaling by SOCS3 Modulate Fasting-Induced Hyperphagia and Weight Regain in Mice.

PubMed

Pedroso, João A B; Silveira, Marina A; Lima, Leandro B; Furigo, Isadora C; Zampieri, Thais T; Ramos-Lobo, Angela M; Buonfiglio, Daniella C; Teixeira, Pryscila D S; Frazão, Renata; Donato, Jose

2016-10-01

Weight regain frequently follows interventions that reduce body weight, leading to a failure in long-term obesity treatment. Inhibitory proteins of the leptin signaling pathway, such as the suppressor of cytokine signaling 3 (SOCS3), have been studied in conditions that predispose animals to obesity. However, whether SOCS3 modulates postrestriction hyperphagia and weight regain remains unknown. Mice lacking SOCS3 protein specifically in leptin receptor (LepR)-expressing cells (LepR SOCS3 knockout [KO]) were generated and studied in fasting and refeeding conditions. LepR SOCS3 KO mice exhibited increased leptin sensitivity in the hypothalamus. Notably, LepR SOCS3 KO males and females showed attenuated food intake and weight regain after 48 hours of fasting. Postrestriction hyperleptinemia was also prevented in LepR SOCS3 KO mice. Next, we studied possible mechanisms and neural circuits involved in the SOCS3 effects. SOCS3 deletion did not prevent fasting- or refeeding-induced c-Fos expression in the arcuate nucleus of the hypothalamus (ARH) nor fasting-induced increased excitability of ARH LepR-expressing cells. On the other hand, SOCS3 ablation reduced the mRNA levels of hypothalamic orexigenic neuropeptides during fasting (neuropeptide Y, agouti-related protein, orexin, and melanin-concentrating hormone). In summary, our findings suggest that increased leptin sensitivity contributes to the maintenance of a reduced body weight after food deprivation. In addition, the attenuated postrestriction food intake observed in mutant mice was not explained by fasting-induced changes in the activity of ARH neurons but exclusively by a lower transcription of orexigenic neuropeptides during fasting. These results indicate a partial dissociation between the regulation of neuronal activity and gene expression in ARH LepR-expressing cells.

The DPP-IV inhibitor linagliptin and GLP-1 induce synergistic effects on body weight loss and appetite suppression in the diet-induced obese rat.

PubMed

Hansen, Henrik H; Hansen, Gitte; Paulsen, Sarah; Vrang, Niels; Mark, Michael; Jelsing, Jacob; Klein, Thomas

2014-10-15

Linagliptin is a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes. DPP-IV inhibitors are considered weight neutral, suggesting that elevation of endogenous incretin levels is not sufficient to promote weight loss per se. Here we evaluated the effect of linagliptin in combination with subcutaneous treatment of GLP-1(7-36) on body weight regulation in diet-induced obese (DIO) rats. Linagliptin administered perorally (1.5mg/kg, b.i.d.), but not subcutaneously (0.5mg/kg, b.i.d.), evoked a very modest body weight loss (2.2%) after 28 days of treatment. GLP-1 (0.5mg/kg, s.c.) treatment alone induced a body weight loss of 4.1%. In contrast, combined linagliptin (1.5mg/kg, p.o., or 0.5mg/kg, s.c.) and GLP-1 (0.5mg/kg) treatment evoked a marked anorectic response with both routes of linagliptin administration being equally effective on final body weight loss (7.5-8.0%). In comparison, liraglutide monotherapy (0.2mg/kg, s.c., b.i.d.) reduced body weight by 10.1%. Interestingly, the weight lowering effect of combined linagliptin and GLP-1 treatment was associated with a marked increase in chow preference, being more pronounced as compared to liraglutide treatment. In addition, linagliptin and GLP-1 co-treatment, but not liraglutide, specifically increased prepro-dynorphin mRNA levels in the caudate-putamen, an effect not obtained with administration of the compounds individually. In conclusion, co-treatment with linagliptin and GLP-1 synergistically reduces body weight in obese rats. The anti-obesity effect was caused by appetite suppression with a concomitant change in diet preference, which may potentially be associated with increased dynorphin activity in forebrain regions involved in reward anticipation and habit learning. Copyright © 2014 Elsevier B.V. All rights reserved.

[Atypical antipsychotic-induced weight gain].

PubMed

Godlewska, Beata R; Olajossy-Hilkesberger, Luiza; Marmurowska-Michałowska, Halina; Olajossy, Marcin; Landowski, Jerzy

2006-01-01

Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.

High molecular weight of polysaccharides from Hericium erinaceus against amyloid beta-induced neurotoxicity.

PubMed

Cheng, Jai-Hong; Tsai, Chia-Ling; Lien, Yi-Yang; Lee, Meng-Shiou; Sheu, Shyang-Chwen

2016-06-07

Hericium erinaceus (HE) is a well-known mushroom in traditional Chinese food and medicine. HE extracts from the fruiting body and mycelia not only exhibit immunomodulatory, antimutagenic and antitumor activity but also have neuroprotective properties. Here, we purified HE polysaccharides (HEPS), composed of two high molecular weight polysaccharides (1.7 × 10(5) Da and 1.1 × 10(5) Da), and evaluated their protective effects on amyloid beta (Aβ)-induced neurotoxicity in rat pheochromocytoma PC12 cells. HEPS were prepared and purified using a 95 % ethanol extraction method. The components of HEPS were analyzed and the molecular weights of the polysaccharides were determined using high-pressure liquid chromatography (HPLC). The neuroprotective effects of the polysaccharides were evaluated through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and an MTT assay and by quantifying reactive oxygen species (ROS) and mitochondrial membrane potentials (MMP) of Aβ-induced neurotoxicity in cells. Our results showed that 250 μg/ml HEPS was harmless and promoted cell viability with 1.2 μM Aβ treatment. We observed that the free radical scavenging rate exceeded 90 % when the concentration of HEPS was higher than 1 mg/mL in cells. The HEPS decreased the production of ROS from 80 to 58 % in a dose-dependent manner. Cell pretreatment with 250 μg/mL HEPS significantly reduced Aβ-induced high MMPs from 74 to 51 % and 94 to 62 % at 24 and 48 h, respectively. Finally, 250 μg/mL of HEPS prevented Aβ-induced cell shrinkage and nuclear degradation of PC12 cells. Our results demonstrate that HEPS exhibit antioxidant and neuroprotective effects on Aβ-induced neurotoxicity in neurons.

Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice.

PubMed

Garcia, Jose M; Scherer, Thomas; Chen, Ji-an; Guillory, Bobby; Nassif, Anriada; Papusha, Victor; Smiechowska, Joanna; Asnicar, Mark; Buettner, Christoph; Smith, Roy G

2013-09-01

Cachexia, defined as an involuntary weight loss ≥ 5%, is a serious and dose-limiting side effect of chemotherapy that decreases survival in cancer patients. Alterations in lipid metabolism are thought to cause the lipodystrophy commonly associated with cachexia. Ghrelin has been proposed to ameliorate the alterations in lipid metabolism due to its orexigenic and anabolic properties. However, the mechanisms of action through which ghrelin could potentially ameliorate chemotherapy-associated cachexia have not been elucidated. The objectives of this study were to identify mechanisms by which the chemotherapeutic agent cisplatin alters lipid metabolism and to establish the role of ghrelin in reversing cachexia. Cisplatin-induced weight and fat loss were prevented by ghrelin. Cisplatin increased markers of lipolysis in white adipose tissue (WAT) and of β-oxidation in liver and WAT and suppressed lipogenesis in liver, WAT, and muscle. Ghrelin prevented the imbalance between lipolysis, β-oxidation, and lipogenesis in WAT and muscle. Pair-feeding experiments demonstrated that the effects of cisplatin and ghrelin on lipogenesis, but not on lipolysis and β-oxidation, were due to a reduction in food intake. Thus, ghrelin prevents cisplatin-induced weight and fat loss by restoring adipose tissue functionality. An increase in caloric intake further enhances the anabolic effects of ghrelin.

Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Wink, Logan K.; Adams, Ryan; Pedapati, Ernest V.; Dominick, Kelli C.; Fox, Emma; Buck, Catherine; Erickson, Craig A.

2017-01-01

Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of…

Low molecular weight heparin restores antithrombin III activity from hyperglycemia induced alterations.

PubMed

Ceriello, A; Marchi, E; Palazzni, E; Quatraro, A; Giugliano, D

1990-01-01

Alteration of antithrombin III (ATIII) activity, glycemia level dependent, exists in diabetes mellitus. In this study the ability of a low molecular weight heparin (LMWH) (Fluxum, Alfa-Wassermann S.p.A., Bologna, Italy), as well as unfractioned héparin, to preserve ATIII activity from glucose-induced alterations, both in vitro and in vivo, is reported. The subcutaneous and intravenous LMWH and heparin administration increases basal depressed ATIII activity in diabetic patients. Heparin shows an equivalent effect on both anti-IIa and anti-Xa activity of ATIII, while LMWH is more effective in preserving the anti-Xa activity. Similarity, heparin preserves ATIII activity from hyperglycemia-induced alterations, during hyperglycemic clamp, and LMWH infusion is able to preserve a significant amount of anti-Xa activity from glucose-induced alterations. Since diabetic patients show a high incidence of thrombotic accidents, LMWH appears to be a promising innovation for the prevention of diabetic thrombophylia.

[Acupuncture Intervention Reduced Weight Gain Induced by Hypoglycemic Agents through Food Intake-related Targets in Central Nervous System].

PubMed

Jing, Xin-yue; Ou, Chen; Lu, Sheng-feng; Zhu, Bing-mei

2015-12-01

Clinical practice shows that thiazolidinediones (TZDs) induce weight gain in patients with type-II diabetes mellitus during treatment, which restrains its application and generalization clinically. It has been demonstrated that acupuncture therapy is useful in easing obesity in clinical trials. In the present paper, we summarize the underlying mechanism of weight gain induced by TZDs through food intake-related targets in the central nervous system and analyze the possible effects of acupuncture therapy. Acupuncture therapy is expected to reduce weight gain side effect of TZDs through 1) lowering permeability of blood brain barrier to reduce TZDs concentration in the brain, 2) upregulating the expression of hypothalamic leptin and inhibiting hypothalamic neuropiptide Y expression, and 3) down-regulating activities of peroxisome proliferator-activated receptor to reduce energy intake and fat syntheses.

Effect of diet-induced weight loss on lipoprotein(a) levels in obese individuals with and without type 2 diabetes.

PubMed

Berk, Kirsten A; Yahya, Reyhana; Verhoeven, Adrie J M; Touw, Jeanette; Leijten, Frank P; van Rossum, Elisabeth F; Wester, Vincent L; Lips, Mirjam A; Pijl, Hanno; Timman, Reinier; Erhart, Gertraud; Kronenberg, Florian; Roeters van Lennep, Jeanine E; Sijbrands, Eric J G; Mulder, Monique T

2017-06-01

Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for cardiovascular disease (CVD), particularly in individuals with type 2 diabetes. Although weight loss improves conventional risk factors for CVD in type 2 diabetes, the effects on Lp(a) are unknown and may influence the long-term outcome of CVD after diet-induced weight loss. The aim of this clinical study was to determine the effect of diet-induced weight loss on Lp(a) levels in obese individuals with type 2 diabetes. Plasma Lp(a) levels were determined by immunoturbidimetry in plasma obtained before and after 3-4 months of an energy-restricted diet in four independent study cohorts. The primary cohort consisted of 131 predominantly obese patients with type 2 diabetes (cohort 1), all participants of the Prevention Of Weight Regain in diabetes type 2 (POWER) trial. The secondary cohorts consisted of 30 obese patients with type 2 diabetes (cohort 2), 37 obese individuals without type 2 diabetes (cohort 3) and 26 obese individuals without type 2 diabetes who underwent bariatric surgery (cohort 4). In the primary cohort, the energy-restricted diet resulted in a weight loss of 9.9% (95% CI 8.9, 10.8) and improved conventional CVD risk factors such as LDL-cholesterol levels. Lp(a) levels increased by 14.8 nmol/l (95% CI 10.2, 20.6). In univariate analysis, the change in Lp(a) correlated with baseline Lp(a) levels (r = 0.38, p < 0.001) and change in LDL-cholesterol (r = 0.19, p = 0.033). In cohorts 2 and 3, the weight loss of 8.5% (95% CI 6.5, 10.6) and 6.5% (95% CI 5.7, 7.2) was accompanied by a median increase in Lp(a) of 13.5 nmol/l (95% CI 2.3, 30.0) and 11.9 nmol/l (95% CI 5.7, 19.0), respectively (all p < 0.05). When cohorts 1-3 were combined, the diet-induced increase in Lp(a) correlated with weight loss (r = 0.178, p = 0.012). In cohort 4, no significant change in Lp(a) was found (-7.0 nmol/l; 95% CI -18.8, 5.3) despite considerable weight loss (14.0%; 95% CI 12.2, 15

The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.

PubMed

Poyurovsky, Michael; Pashinian, Artashes; Levi, Aya; Weizman, Ronit; Weizman, Abraham

2005-03-01

Histamine antagonism has been implicated in antipsychotic drug-induced weight gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in three first-episode schizophrenia patients for 6 weeks. Body weight was measured at baseline and weekly thereafter. Clinical rating scales were completed at baseline and at week 6. All participants gained weight (mean weight gain 3.1+/-0.9 kg) and a similar pattern of weight gain was observed: an increase during the first 2 weeks and no additional weight gain (two patients) or minor weight loss (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the cut-off for clinically significant weight gain. Betahistine was safe and well tolerated and did not interfere with the antipsychotic effect of olanzapine. Our findings justify a placebo-controlled evaluation of the putative weight-attenuating effect of betahistine in olanzapine-induced weight gain.

Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice.

PubMed

Seimon, Radhika V; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A; Nguyen, Amy D; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F; Lau, Jackie; Herzog, Herbert; Sainsbury, Amanda

2016-01-01

Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)-(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups. Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative to energy

High-performance liquid chromatographic enantioseparation of unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids on macrocyclic glycopeptide-based chiral stationary phases.

PubMed

Sipos, László; Ilisz, István; Nonn, Melinda; Fülöp, Ferenc; Pataj, Zoltán; Armstrong, Daniel W; Péter, Antal

2012-04-06

The enantiomers of four unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids were directly separated on chiral stationary phases containing macrocyclic glycopeptide antibiotics teicoplanin (Astec Chirobiotic T and T2), teicoplanin aglycone (Chirobiotic TAG), vancomycin (Chirobiotic V) and vancomycin aglycone (Chirobiotic VAG) as chiral selectors. The effects of the mobile phase composition, the structure of the analytes and temperature on the separations were investigated. Experiments were performed at constant mobile phase compositions in the temperature range 5-45 °C to study the effects of temperature, and thermodynamic parameters were calculated from plots of lnk or lnα versus 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantiomeric separations were in most cases enthalpy-driven. The sequence of elution of the enantiomers was determined in all cases. Copyright © 2011 Elsevier B.V. All rights reserved.

Pharmacological Strategies to Counteract Antipsychotic-Induced Weight Gain and Metabolic Adverse Effects in Schizophrenia: A Systematic Review and Meta-analysis

PubMed Central

Mizuno, Yuya; Suzuki, Takefumi; Nakagawa, Atsuo; Yoshida, Kazunari; Mimura, Masaru; Fleischhacker, Walter Wolfgang; Uchida, Hiroyuki

2014-01-01

Background: Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. Objective: To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Data Sources: Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Study Selection: Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Data Extraction: Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Data Synthesis: Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to −3.17 kg (95% CI: −4.44 to −1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. Conclusion: When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia. PMID:24636967

N-linked (N-) glycoproteomics of urinary exosomes. [Corrected].

PubMed

Saraswat, Mayank; Joenväära, Sakari; Musante, Luca; Peltoniemi, Hannu; Holthofer, Harry; Renkonen, Risto

2015-02-01

Epithelial cells lining the urinary tract secrete urinary exosomes (40-100 nm) that can be targeted to specific cells modulating their functionality. One potential targeting mechanism is adhesion between vesicle surface glycoproteins and target cells. This makes the glycopeptide analysis of exosomes important. Exosomes reflect the physiological state of the parent cells; therefore, they are a good source of biomarkers for urological and other diseases. Moreover, the urine collection is easy and noninvasive and urinary exosomes give information about renal and systemic organ systems. Accordingly, multiple studies on proteomic characterization of urinary exosomes in health and disease have been published. However, no systematic analysis of their glycoproteomic profile has been carried out to date, whereas a conserved glycan signature has been found for exosomes from urine and other sources including T cell lines and human milk. Here, we have enriched and identified the N-glycopeptides from these vesicles. These enriched N-glycopeptides were solved for their peptide sequence, glycan composition, structure, and glycosylation site using collision-induced dissociation MS/MS (CID-tandem MS) data interpreted by a publicly available software GlycopeptideId. Released glycans from the same sample was also analyzed with MALDI-MS. We have identified the N-glycoproteome of urinary exosomes. In total 126 N-glycopeptides from 51 N-glycosylation sites belonging to 37 glycoproteins were found in our results. The peptide sequences of these N-glycopeptides were identified unambiguously and their glycan composition (for 125 N-glycopeptides) and structures (for 87 N-glycopeptides) were proposed. A corresponding glycomic analysis with released N-glycans was also performed. We identified 66 unique nonmodified N-glycan compositions and in addition 13 sulfated/phosphorylated glycans were also found. This is the first systematic analysis of N-glycoproteome of urinary exosomes. © 2015 by The

[Cyanidin-3-glucoside attenuates body weight gain, serum lipid concentrations and insulin resistance in high-fat diet-induced obese rats].

PubMed

Yu, Ren-Qiang; Wu, Xiao-You; Zhou, Xiang; Zhu, Jing; Ma, Lu-Yi

2014-05-01

Cyanidin-3-glucoside (C3G) is the main active ingredient of anthocyanidin. This study aimed to evaluate the effects of C3G on body weight gain, visceral adiposity, lipid profiles and insulin resistance in high-fat diet-induced obese rats. Thirty male Sprague-Dawley rats were randomly divided into a control group (n=8) and a high fat diet group (n=22), and were fed with standard diet or high fat diet. Five weeks later, 17 high-fat diet-induced obese rats were randomly given C3G [100 mg/(kg·d)] or normal saline via intragastric administration for 5 weeks. Five weeks later, body weight, visceral adiposity and food intake were measured. Blood samples were collected for detecting fasting glucose, serum insulin, lipid profiles and adiponectin. Insulin resistance index, atherosclerosis index and average feed efficiency ratio were calculated. C3G supplementation markedly decreased body weight, visceral adiposity, average feed efficiency ratio, triglyceride, total cholesterol, low density lipoprotein cholesterol, fasting glucose, serum insulin, insulin resistance index and atherosclerosis index in high-fat diet-induced obese rats. C3G supplementation normalized serum adiponectin and high density lipoprotein cholesterol levels in high-fat diet-induced obese rats. Cyanidin-3-glucoside can reduce body weight gain, and attenuate obesity-associated dyslipidemia and insulin resistance in high-fat diet-fed rats via up-regulating serum adiponectin level.

Illustrative examples of probable transfer of resistance determinants from food animals to humans: Streptothricins, glycopeptides, and colistin

PubMed Central

Webb, Hattie E.; Angulo, Frederick J.; Granier, Sophie A.; Scott, H. Morgan; Loneragan, Guy H.

2017-01-01

Use, overuse, and misuse of antimicrobials contributes to selection and dissemination of bacterial resistance determinants that may be transferred to humans and constitute a global public health concern. Because of the continued emergence and expansion of antimicrobial resistance, combined with the lack of novel antimicrobial agents, efforts are underway to preserve the efficacy of current available life-saving antimicrobials in humans. As a result, uses of medically important antimicrobials in food animal production have generated debate and led to calls to reduce both antimicrobial use and the need for use. This manuscript, commissioned by the World Health Organization (WHO) to help inform the development of the WHO guidelines on the use of medically important antimicrobials in food animals, includes three illustrations of antimicrobial use in food animal production that has contributed to the selection—and subsequent transfer—of resistance determinants from food animals to humans. Herein, antimicrobial use and the epidemiology of bacterial resistance are described for streptothricins, glycopeptides, and colistin. Taken together, these historical and current narratives reinforce the need for actions that will preserve the efficacy of antimicrobials. PMID:29188021

The ABC transporter Tba of Amycolatopsis balhimycina is required for efficient export of the glycopeptide antibiotic balhimycin.

PubMed

Menges, R; Muth, G; Wohlleben, W; Stegmann, E

2007-11-01

All known gene clusters for glycopeptide antibiotic biosynthesis contain a conserved gene supposed to encode an ABC-transporter. In the balhimycin-producer Amycolatopsis balhimycina this gene (tba) is localised between the prephenate dehydrogenase gene pdh and the peptide synthetase gene bpsA. Inactivation of tba in A. balhimycina by gene replacement did not interfere with growth and did not affect balhimycin resistance. However, in the supernatant of the tba mutant RM43 less balhimycin was accumulated compared to the wild type; and the intra-cellular balhimycin concentration was ten times higher in the tba mutant RM43 than in the wild type. These data suggest that the ABC transporter encoded in the balhimycin biosynthesis gene cluster is not involved in resistance but is required for the efficient export of the antibiotic. To elucidate the activity of Tba it was heterologously expressed in Escherichia coli with an N-terminal His-tag and purified by nickel chromatography. A photometric assay revealed that His(6)-Tba solubilised in dodecylmaltoside possesses ATPase activity, characteristic for ABC-transporters.

Exercise, appetite and weight management: understanding the compensatory responses in eating behaviour and how they contribute to variability in exercise-induced weight loss.

PubMed

King, N A; Horner, K; Hills, A P; Byrne, N M; Wood, R E; Bryant, E; Caudwell, P; Finlayson, G; Gibbons, C; Hopkins, M; Martins, C; Blundell, J E

2012-04-01

Does exercise promote weight loss? One of the key problems with studies assessing the efficacy of exercise as a method of weight management and obesity is that mean data are presented and the individual variability in response is overlooked. Recent data have highlighted the need to demonstrate and characterise the individual variability in response to exercise. Do people who exercise compensate for the increase in energy expenditure via compensatory increases in hunger and food intake? The authors address the physiological, psychological and behavioural factors potentially involved in the relationship between exercise and appetite, and identify the research questions that remain unanswered. A negative consequence of the phenomena of individual variability and compensatory responses has been the focus on those who lose little weight in response to exercise; this has been used unreasonably as evidence to suggest that exercise is a futile method of controlling weight and managing obesity. Most of the evidence suggests that exercise is useful for improving body composition and health. For example, when exercise-induced mean weight loss is <1.0 kg, significant improvements in aerobic capacity (+6.3 ml/kg/min), systolic (-6.00 mm Hg) and diastolic (-3.9 mm Hg) blood pressure, waist circumference (-3.7 cm) and positive mood still occur. However, people will vary in their responses to exercise; understanding and characterising this variability will help tailor weight loss strategies to suit individuals.

Transport stress induces weight loss and heart injury in chicks: disruption of ionic homeostasis via modulating ion transporting ATPases

PubMed Central

Xia, Jun; Li, Xue-Nan; Ge, Jing; Zhang, Cong; Li, Jin-Long

2017-01-01

Transportation is inevitable in the poultry industry, and it can induce stress to chicks in varying degrees, such as mild discomfort, sometimes even death. However, the research about the effects of transport stress on the weight loss and heart injury of chicks is lacking. To elucidate the underlying mechanism of transport stress-induced effects, chicks were transported for 2h, 4h and 8h. The creatinine kinase (CK) activities, the ionic contents, the ATPases activities and the transcription of the ATPase associated subunits in chick heart were detected. The results showed that transport stress increased the weight loss and the CK activity, disturbed the ionic (K+, Ca2+, Mg2+) homeostasis and inhibited the ATPase (Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and Ca2+-Mg2+-ATPase) activities, increased the ATP content and downregulated the gene expression levels of the ATPase associated subunits in heart. In conclusion, transport stress disturbed the ionic homeostasis via modulating ion transporting ATPases and the transcriptions of the associated subunits, and ultimately induced weight loss and heart injury in chicks. PMID:28445983

Quality of Life after Diet or Exercise-Induced Weight Loss in Overweight to Obese Postmenopausal Women: The SHAPE-2 Randomised Controlled Trial.

PubMed

van Gemert, Willemijn A M; van der Palen, Job; Monninkhof, Evelyn M; Rozeboom, Anouk; Peters, Roelof; Wittink, Harriet; Schuit, Albertine J; Peeters, Petra H

2015-01-01

This study investigates the effect of a modest weight loss either by a calorie restricted diet or mainly by increased physical exercise on health related quality of life (HRQoL) in overweight-to-obese and inactive postmenopausal women. We hypothesize that HRQoL improves with weight loss, and that exercise-induced weight loss is more effective for this than diet-induced weight loss. The SHAPE-2 trial was primarily designed to evaluate any additional effect of weight loss by exercise compared with a comparable amount of weight loss by diet on biomarkers relevant for breast cancer risk. In the present analysis we focus on HRQoL. We randomly assigned 243 eligible women to a diet (n = 97), exercise (n = 98), or control group (n = 48). Both interventions aimed for 5-6 kg weight loss. HRQoL was measured at baseline and after 16 weeks by the SF-36 questionnaire. Data of 214 women were available for analysis. Weight loss was 4.9 kg (6.1%) and 5.5 kg (6.9%) with diet and exercise, respectively. Scores of the SF-36 domain 'health change' increased significantly by 8.8 points (95% CI 1.6;16.1) with diet, and by 20.5 points (95% CI 13.2;27.7) with exercise when compared with control. Direct comparison of diet and exercise showed a statistically significantly stronger improvement with exercise. Both intervention groups showed a tendency towards improvements in most other domains, which were more pronounced in the exercise group, but not statistically different from control or each other. In a randomized trial in overweight-to-obese and inactive postmenopausal women a comparable 6%-7% weight loss was achieved by diet-only or mainly by exercise and showed improvements in physical and mental HRQoL domains, but results were not statistically significant in either the diet or exercise group. However, a modest weight loss does lead to a positive change in self-perceived health status. This effect was significantly larger with exercise-induced weight loss than with comparable diet-induced

High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women.

PubMed

Smith, Gordon I; Yoshino, Jun; Kelly, Shannon C; Reeds, Dominic N; Okunade, Adewole; Patterson, Bruce W; Klein, Samuel; Mittendorfer, Bettina

2016-10-11

High-protein (HP) intake during weight loss (WL) therapy is often recommended because it reduces the loss of lean tissue mass. However, HP intake could have adverse effects on metabolic function, because protein ingestion reduces postprandial insulin sensitivity. In this study, we compared the effects of ∼10% WL with a hypocaloric diet containing 0.8 g protein/kg/day and a hypocaloric diet containing 1.2 g protein/kg/day on muscle insulin action in postmenopausal women with obesity. We found that HP intake reduced the WL-induced decline in lean tissue mass by ∼45%. However, HP intake also prevented the WL-induced improvements in muscle insulin signaling and insulin-stimulated glucose uptake, as well as the WL-induced adaptations in oxidative stress and cell structural biology pathways. Our data demonstrate that the protein content of a WL diet can have profound effects on metabolic function and underscore the importance of considering dietary macronutrient composition during WL therapy for people with obesity. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

PubMed Central

Seimon, Radhika V.; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A.; Nguyen, Amy D.; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F.; Lau, Jackie

2016-01-01

Background Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Methods Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5–6 consecutive days, and ad libitum intake for 1–3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)–(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Results Mice on the ID showed transient hyperphagia relative to controls during each 1–3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups. Conclusion Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces

Sibutramine in the treatment of antipsychotic-induced weight gain: a pilot study in patients with schizophrenia.

PubMed

Biedermann, Falko; Fleischhacker, W Wolfgang; Kemmler, Georg; Ebenbichler, Christoph F; Lechleitner, Monika; Hofer, Alex

2014-05-01

Weight gain represents a frequent side effect of antipsychotic drug treatment. The current trial investigated the effect of add-on treatment with sibutramine in schizophrenia outpatients who had gained more than 7% of weight during the course of treatment. This 24-week placebo-controlled study evaluated the effects of sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio, BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several laboratory tests were performed. Psychopathological symptoms and side effects were assessed frequently. Fifteen patients were assigned randomly to add-on treatment with sibutramine 10 mg or placebo. The two groups did not differ in weight, sociodemographic, or clinical data. Eleven patients were considered for statistical analysis. Significant weight loss was observed in the sibutramine group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in the placebo group. No significant between-group differences were found in changes in psychopathology or drug safety. This pilot trial suggests that adjunctive treatment with sibutramine may be safe and effective in schizophrenic patients with antipsychotic-induced weight gain.

Effectiveness of a structured diet program in antipsychotic-induced weight gain in patients with schizophrenia.

PubMed

Direk, Nese; Ucok, Alp

2008-01-01

Objective.The aim of this study was to evaluate the effectiveness of a structured diet program in weight loss in patients with schizophrenia. Methods. A total of 38 outpatients diagnosed with schizophrenia according to DSM-IV and who had complaints of weight gain during treatment with various antipsychotic drugs were invited to participate in a 3-month structured diet program. Thirty-two patients and another 40 patients were included as the control group. At the beginning of the diet program, the patients were given a form in order to evaluate their eating habits, and blood samples were taken to measure plasma lipid profile, and fasting blood glucose (FBG) level. Patients' baseline weight, body mass index (BMI), and basal metabolism rate (BMR) were recorded. Results. Thirty-two patients with schizophrenia, who attended a 3-month structured diet program had mean weight loss of 6.19 kg, whereas patients in the control group gained 1.6 kg. Conclusion. Our findings show that a diet program is effective in managing antipsychotic-induced weight gain. The degree of weight loss seems to be correlated with the duration in which the patient is on the diet program. However; younger patients had less benefit from the diet program.

Effects of low-molecular-weight-chitosan on the adenine-induced chronic renal failure rats in vitro and in vivo

NASA Astrophysics Data System (ADS)

Zhi, Xuan; Han, Baoqin; Sui, Xianxian; Hu, Rui; Liu, Wanshun

2015-02-01

The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37° for 24 h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growth. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The results after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100 mg kg-1 d-1.

Polysaccharide peptide isolated from grass-cultured Ganoderma lucidum induces anti-proliferative and pro-apoptotic effects in the human U251 glioma cell line

PubMed Central

Wang, Chunhua; Lin, Dongmei; Chen, Quan; Lin, Shuqian; Shi, Songsheng; Chen, Chunmei

2018-01-01

The Ganoderma lucidum (G. lucidum) mushroom is one of the most extensively studied functional foods, known for its numerous health benefits, including the inhibition of tumor cell growth. The present study assessed the anti-proliferative and pro-apoptotic activity of a novel G. lucidum polysaccharide peptide (GL-PP) in human glioma U251 cells, which was purified from grass-cultured G. lucidum. GL-PP is a glycopeptide with an average molecular weight of 42,635 Da and a polysaccharide-to-peptide ratio of 88.70:11.30. The polysaccharides were composed of l-arabinose, d-mannose and d-glucose at a molar ratio of 1.329:0.372:2.953 and a total of 17 amino acids were detected. The results of the current study demonstrated that GL-PP significantly inhibited U251 cellular proliferation. The proportion of G0/G1 phase cells and sub-G1 phase cells significantly increased as the concentration of GL-PP increased, as did the activity of caspase-3. These results indicate that GL-PP directly inhibited human glioma U251 proliferation by inducing cell cycle arrest and promoting apoptosis. PMID:29541200

Polysaccharide peptide isolated from grass-cultured Ganoderma lucidum induces anti-proliferative and pro-apoptotic effects in the human U251 glioma cell line.

PubMed

Wang, Chunhua; Lin, Dongmei; Chen, Quan; Lin, Shuqian; Shi, Songsheng; Chen, Chunmei

2018-04-01

The Ganoderma lucidum ( G. lucidum ) mushroom is one of the most extensively studied functional foods, known for its numerous health benefits, including the inhibition of tumor cell growth. The present study assessed the anti-proliferative and pro-apoptotic activity of a novel G. lucidum polysaccharide peptide (GL-PP) in human glioma U251 cells, which was purified from grass-cultured G. lucidum . GL-PP is a glycopeptide with an average molecular weight of 42,635 Da and a polysaccharide-to-peptide ratio of 88.70:11.30. The polysaccharides were composed of l-arabinose, d-mannose and d-glucose at a molar ratio of 1.329:0.372:2.953 and a total of 17 amino acids were detected. The results of the current study demonstrated that GL-PP significantly inhibited U251 cellular proliferation. The proportion of G 0 /G 1 phase cells and sub-G 1 phase cells significantly increased as the concentration of GL-PP increased, as did the activity of caspase-3. These results indicate that GL-PP directly inhibited human glioma U251 proliferation by inducing cell cycle arrest and promoting apoptosis.

Importance of early weight changes to predict long-term weight gain during psychotropic drug treatment.

PubMed

Vandenberghe, Frederik; Gholam-Rezaee, Mehdi; Saigí-Morgui, Núria; Delacrétaz, Aurélie; Choong, Eva; Solida-Tozzi, Alessandra; Kolly, Stéphane; Thonney, Jacques; Gallo, Sylfa Fassassi; Hedjal, Ahmed; Ambresin, Anne-Emmanuelle; von Gunten, Armin; Conus, Philippe; Eap, Chin B

2015-11-01

Psychotropic drugs can induce substantial weight gain, particularly during the first 6 months of treatment. The authors aimed to determine the potential predictive power of an early weight gain after the introduction of weight gain-inducing psychotropic drugs on long-term weight gain. Data were obtained from a 1-year longitudinal study ongoing since 2007 including 351 psychiatric (ICD-10) patients, with metabolic parameters monitored (baseline and/or 1, 3, 6, 9, 12 months) and with compliance ascertained. International Diabetes Federation and World Health Organization definitions were used to define metabolic syndrome and obesity, respectively. Prevalences of metabolic syndrome and obesity were 22% and 17%, respectively, at baseline and 32% and 24% after 1 year. Receiver operating characteristic analyses indicated that an early weight gain > 5% after a period of 1 month is the best predictor for important long-term weight gain (≥ 15% after 3 months: sensitivity, 67%; specificity, 88%; ≥ 20% after 12 months: sensitivity, 47%; specificity, 89%). This analysis identified most patients (97% for 3 months, 93% for 12 months) who had weight gain ≤ 5% after 1 month as continuing to have a moderate weight gain after 3 and 12 months. Its predictive power was confirmed by fitting a longitudinal multivariate model (difference between groups in 1 year of 6.4% weight increase as compared to baseline, P = .0001). Following prescription of weight gain-inducing psychotropic drugs, a 5% threshold for weight gain after 1 month should raise clinician concerns about weight-controlling strategies. © Copyright 2015 Physicians Postgraduate Press, Inc.

The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat.

PubMed

Martins, C; Kulseng, B; King, N A; Holst, J J; Blundell, J E

2010-04-01

The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic and anorexigenic peptides. The aim of the study was to investigate the effects of medium-term exercise on fasting/postprandial levels of appetite-related hormones and subjective appetite sensations in overweight/obese individuals. We conducted a longitudinal study in a university research center. Twenty-two sedentary overweight/obese individuals (age, 36.9 +/- 8.3 yr; body mass index, 31.3 +/- 3.3 kg/m(2)) took part in a 12-wk supervised exercise programme (five times per week, 75% maximal heart rate) and were requested not to change their food intake during the study. We measured changes in body weight and fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite. Exercise resulted in a significant reduction in body weight and fasting insulin and an increase in AG plasma levels and fasting hunger sensations. A significant reduction in postprandial insulin plasma levels and a tendency toward an increase in the delayed release of glucagon-like peptide-1 (90-180 min) were also observed after exercise, as well as a significant increase (127%) in the suppression of AG postprandially. Exercise-induced weight loss is associated with physiological and biopsychological changes toward an increased drive to eat in the fasting state. However, this seems to be balanced by an improved satiety response to a meal and improved sensitivity of the appetite control system.

Rats fed only during the light period are resistant to stress-induced weight loss.

PubMed

Harris, Ruth B S; Zhou, Jun; Mitchell, Tiffany; Hebert, Sadie; Ryan, Donna H

2002-08-01

Repeated restraint stress (3 h/day for 3 days) causes a chronic down-regulation of body weight in rats. This study determined whether weight loss was influenced by the time of day that rats had access to food or that stress was applied. Groups of male Sprague-Dawley rats were fed a 40% kcal fat diet with food given ad libitum, only during the light phase or only during the dark phase. After 2 weeks of adaptation, rats within each feeding treatment were divided into four groups. One was exposed to repeated restraint at the start of the light phase, another was restrained at the start of the dark phase and the remaining groups were nonstressed controls for restrained rats. Body weight was significantly reduced in ad libitum- and dark-fed restrained rats, compared with nonstressed controls, from Day 2 of restraint, regardless of the time of day that they were stressed. There was no significant effect of restraint on weight change of light-fed rats. Food intake was inhibited by stress in ad libitum- and dark-fed rats, but it was not changed in light-fed rats. Serum corticosterone was increased by restraint in all rats irrespective of feeding schedule. This study demonstrates that stress-induced weight loss only occurs when rats have food available during their normal feeding period (dark phase) and is not determined by increased corticosterone release.

Tributyltin exposure induces gut microbiome dysbiosis with increased body weight gain and dyslipidemia in mice.

PubMed

Guo, Hao; Yan, Haotian; Cheng, Dong; Wei, Xinglong; Kou, Ruirui; Si, Jiliang

2018-05-03

Gut microbiome dysbiosis plays a profound role in the pathogenesis of obesity and tributyltin (TBT) has been found as an environmental obesogen. However, whether TBT could disturb gut microbiome and the relationship between obesity induced by TBT exposure and alteration in gut microbiota are still unknown. In order to assess the association between them, mice were exposed to TBTCl (50 μg kg -1 ) once every three days from postnatal days (PNDs) 24 to 54. The results demonstrated that TBT exposure resulted in increased body weight gain, lager visceral fat accumulation and dyslipidemia in male mice on PND 84. Correspondingly, 16S rRNA gene sequencing revealed that TBT treatment decreased gut microbial species and perturbed the microbiome composition in mice. Furthermore, Pearson's corelation coefficient analysis showed a significantly negative correlation between the body weight and the alpha diversity of gut microbiome. These results suggested that TBT exposure could induce gut microbiome dysbiosis in mice, which might contribute to the obesity pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Weight Loss Behaviors Used by Active Duty Air Force Personnel to Maintain Compliance with Weight Control Standards

DTIC Science & Technology

1997-05-01

lose weight. The methods of weight loss reported were exercising , skipping meals, using diet pills, and self- induced vomiting. In each case, females...Restrictive Diet Popular Diet Self- induced Vomifing Laxatives Diuretics Diet Pills Exercise Other Note- N = frequency of resf were allowed to...Rate 69 Demographic Data 69 Exercise 70 Weight Loss Beliefs and Practices 71 Additional Data Collected 76 Implications for Military Health Care

Preferential reductions in intermuscular and visceral adipose tissue with exercise-induced weight loss compared with calorie restriction

PubMed Central

Murphy, Joan C.; McDaniel, Jennifer L.; Mora, Katherine; Villareal, Dennis T.; Fontana, Luigi

2012-01-01

Intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) are associated with insulin resistance. We sought to determine whether exercise-induced weight loss (EX) results in greater reductions in IMAT and VAT compared with similar weight loss induced by calorie restriction (CR) and whether these changes are associated with improvements in glucoregulation. Sedentary men and women (50–60 yr; body mass index of 23.5–29.9 kg/m2) were randomized to 1 yr of CR (n = 17), EX (n = 16), or a control group (CON; n = 6). Bilateral thigh IMAT and VAT volumes were quantified using multi-slice magnetic resonance imaging. Insulin sensitivity index (ISI) was determined from oral glucose tolerance test glucose and insulin levels. Weight loss was comparable (P = 0.25) in the CR (−10.8 ± 1.4%) and EX groups (−8.3 ± 1.5%) and greater than in the control group (−2.0 ± 2.4%; P < 0.05). IMAT and VAT reductions were larger in the CR and EX groups than in the CON group (P ≤ 0.05). After controlling for differences in total fat mass change between the CR and EX groups, IMAT and VAT reductions were nearly twofold greater (P ≤ 0.05) in the EX group than in the CR group (IMAT: −45 ±5 vs. −25 ± 5 ml; VAT: −490 ± 64 vs. −267 ± 61 ml). In the EX group, the reductions in IMAT were correlated with increases in ISI (r = −0.71; P = 0.003), whereas in the CR group, VAT reductions were correlated with increases in ISI (r = −0.64; P = 0.006). In conclusion, calorie restriction and exercise-induced weight loss both decrease IMAT and VAT volumes. However, exercise appears to result in preferential reductions in these fat depots. PMID:22016371

Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague-Dawley rats.

PubMed

Rojas, J M; Printz, R L; Niswender, K D

2011-07-04

Initiation and intensification of insulin therapy commonly causes weight gain, a barrier to therapy. A contrasting body of evidence indicates that insulin functions as an adiposity negative feedback signal and reduces food intake, weight gain and adiposity via action in the central nervous system. Basal insulin analogs, detemir (Det) and glargine (Glar), have been associated with less hypoglycemia compared with neutral protamine hagedorn insulin, and Det with less weight gain, especially in patients with higher body mass index (BMI). We sought to determine whether insulin therapy per se causes body weight and fat mass gain when delivered via a clinically relevant subcutaneous (SC) route in the absence of hypoglycemia and glycosuria in non-diabetic lean and diet-induced obese rats. Rats were exposed to either a low-fat diet (LFD; 13.5% fat) or high-fat diet (HFD; 60% fat), and received Det (0.5 U kg(-1)), Glar (0.2 U kg(-1)) or vehicle (Veh) SC once daily for 4 weeks. These dosages of insulin were equipotent in rats with respect to blood-glucose concentration and did not induce hypoglycemia. As predicted by current models of energy homeostasis, neither insulin Det nor Glar therapy affected food intake and weight gain in LFD rats. Det treatment significantly attenuated food intake, body weight gain and fat mass gain relative to the Glar and Veh in high-fat fed animals, mirroring observations in humans. That neither insulin group gained excess weight, suggests weight gain with SC basal insulin therapy may not be inevitable. Our data further suggest that Det possesses a unique property to attenuate the development of obesity associated with a HFD.

Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.

PubMed

Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria; Füchtbauer, Ernst-Martin; Jørgensen, Signe Marie; Kissow, Hanne-Louise; Nytofte, Nikolaj; Poulsen, Steen Seier; Rosenkilde, Mette Marie; Seino, Yutaka; Thams, Peter; Holst, Peter Johannes; Holst, Jens Juul

2011-12-30

The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass that was similar between the groups. In contrast, glucose-dependent insulinotropic polypeptide-mediated insulin secretion does not seem to be important for regulation of body weight after high fat feeding. The study supports a role of the adipocyte GIPr in nutrient-dependent regulation of body weight and lean mass, but it does not support a direct and independent role for the adipocyte or beta-cell GIPr in promoting adipogenesis.

Cerebral Venous Sinus Thrombosis Due to Low-molecular-weight Heparin-induced Thrombocytopenia.

PubMed

Gleichgerrcht, Ezequiel; Lim, Ming Y; Turan, Tanya N

2017-11-01

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin exposure. A limited number of studies have reported cerebral venous sinus thrombosis (CVST) as the presenting thrombotic event induced by HIT, only one of which occurred with exposure to low-molecular-weight heparin (LMWH), with death as outcome. Here, we present a unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome. A 52-year-old woman received subcutaneous LMWH for deep vein thrombosis prophylaxis while in rehabilitation following kyphoplasty for spinal fracture related to recent trauma. On postoperative day 15, she developed acute onset altered mental status with significant agitation and nonsensical speech and was found to have brain imaging findings suggestive of CVST. Work-up revealed a drop in platelets associated with HIT, which did not improve off heparin products and with steroids, requiring intravenous immunoglobulin therapy, likely due to an overlapping immune thrombocytopenic purpura. Patient was managed on an argatroban drip until platelet count normalized and was able to transition to warfarin. Her clinical outcome was very favorable with near-normal neurological exam except for subtle cognitive changes. This unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome highlights the importance of linking CVST with HIT and of establishing the need for early alternative antithrombotic therapeutic strategies.

[Study the impacts of diagnosis on occupational noise-induced deafness after bring into the different high frequency hearing threshold weighted value].

PubMed

Xue, L J; Yang, A C; Chen, H; Huang, W X; Guo, J J; Liang, X Y; Chen, Z Q; Zheng, Q L

2017-11-20

Objective: Study of the results and the degree on occupational noise-induced deafness in-to the different high frequency hearing threshold weighted value, in order to provide theoretical basis for the re-vision of diagnostic criteria on occupational noise-induced deafness. Methods: A retrospective study was con-ducted to investigate the cases on the diagnosis of occupational noise-induced deafness in Guangdong province hospital for occupational disease prevention and treatment from January 2016 to January 2017. Based on the re-sults of the 3 hearing test for each test interval greater than 3 days in the hospital, the best threshold of each frequency was obtained, and based on the diagnostic criteria of occupational noise deafness in 2007 edition, Chi square test, t test and variance analysis were used to measure SPSS21.0 data, their differences are tested among the means of speech frequency and the high frequency weighted value into different age group, noise ex-posure group, and diagnostic classification between different dimensions. Results: 1. There were totally 168 cases in accordance with the study plan, male 154 cases, female 14 cases, the average age was 41.18 ±6.07 years old. 2. The diagnosis rate was increased into the weighted value of different high frequency than the mean value of pure speech frequency, the weighted 4 kHz frequency increased by 13.69% (χ(2)=9.880, P =0.002) , 6 kHz increased by 15.47% (χ(2)=9.985, P =0.002) and 4 kHz+6 kHz increased by15.47% (χ(2)=9.985, P =0.002) , the difference was statistically significant. The diagnostic rate of different high threshold had no obvious differ-ence between the genders. 3. The age groups were divided into less than or equal to 40years old group (A group) and 40-50 years old group (group B) , there were higher the diagnostic rate between high frequency weighted 4 kHz (A group χ(2)=3.380, P =0.050; B group χ(2)=4.054, P =0.032) , weighted 6 kHz (A group χ(2)=6.362, P =0.012; B group χ(2

Body contouring surgery following bariatric surgery and dietetically induced massive weight reduction: a risk analysis.

PubMed

de Kerviler, S; Hüsler, R; Banic, A; Constantinescu, M A

2009-05-01

This study analyzed the impact of weight reduction method, preoperative, and intraoperative variables on the outcome of reconstructive body contouring surgery following massive weight reduction. All patients presenting with a maximal BMI >/=35 kg/m(2) before weight reduction who underwent body contouring surgery of the trunk following massive weight loss (excess body mass index loss (EBMIL) >/= 30%) between January 2002 and June 2007 were retrospectively analyzed. Incomplete records or follow-up led to exclusion. Statistical analysis focused on weight reduction method and pre-, intra-, and postoperative risk factors. The outcome was compared to current literature results. A total of 104 patients were included (87 female and 17 male; mean age 47.9 years). Massive weight reduction was achieved through bariatric surgery in 62 patients (59.6%) and dietetically in 42 patients (40.4%). Dietetically achieved excess body mass index loss (EBMIL) was 94.20% and in this cohort higher than surgically induced reduction EBMIL 80.80% (p < 0.01). Bariatric surgery did not present increased risks for complications for the secondary body contouring procedures. The observed complications (26.9%) were analyzed for risk factors. Total tissue resection weight was a significant risk factor (p < 0.05). Preoperative BMI had an impact on infections (p < 0.05). No impact on the postoperative outcome was detected in EBMIL, maximal BMI, smoking, hemoglobin, blood loss, body contouring technique or operation time. Corrective procedures were performed in 11 patients (10.6%). The results were compared to recent data. Bariatric surgery does not increase risks for complications in subsequent body contouring procedures when compared to massive dietetic weight reduction.

Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population.

PubMed

Choong, Eva; Bondolfi, Guido; Etter, Manuela; Jermann, Françoise; Aubry, Jean-Michel; Bartolomei, Javier; Gholam-Rezaee, Mehdi; Eap, Chin B

2012-04-01

To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients. This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded. 196 inclusions were completed. Weight gain (≥10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI ≥ 30), hypercholesterolemia (≥6.2 mmol/L) and low HDL-cholesterol (<1.0 mmol/L in men, <1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine > quetiapine or risperidone > lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI. High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement. Copyright © 2012 Elsevier Ltd. All rights reserved.

A novel dual amylin and calcitonin receptor agonist, KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference.

PubMed

Gydesen, Sofie; Hjuler, Sara Toftegaard; Freving, Zenia; Andreassen, Kim Vietz; Sonne, Nina; Hellgren, Lars I; Karsdal, Morten Asser; Henriksen, Kim

2017-04-01

Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities. The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight-independent effects of KBP-089 using a weight-matched group. Rats fed a high-fat diet were treated, s.c., with KBP-089 0.625, 1.25, 2.5 μg·kg -1 or vehicle. KB-089 induced in a dose-dependent and sustained weight loss (~17% by 2.5 μg·kg -1 ). Moreover, KBP-089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP-089 improved glucose homeostasis through improved insulin action. To obtain a weight-matched group, significantly less food was offered (9% less than in the KBP-089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP-089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP-089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle. The novel DACRA, KBP-089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet-induced weight loss. © 2017 The British Pharmacological Society.

Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity.

PubMed

Barquissau, Valentin; Léger, Benjamin; Beuzelin, Diane; Martins, Frédéric; Amri, Ez-Zoubir; Pisani, Didier F; Saris, Wim H M; Astrup, Arne; Maoret, Jean-José; Iacovoni, Jason; Déjean, Sébastien; Moro, Cédric; Viguerie, Nathalie; Langin, Dominique

2018-01-23

Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT). Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Antihyperglycemic effect of Persea duthieion blood glucose levels and body weight in alloxan induced diabetic rabbits.

PubMed

Sultan, Khushbakht; Zakir, Muhammad; Khan, Haroon; Khan, Ihsaan Ullah; Ayaz, Sultan; Khan, Iqbal; Khan, Jafar; Khan, Murad Ali

2016-05-01

The present study was designed to investigate the antihyperglycemic effect of Persea duthieion blood glucose concentration and body weight in alloxan induced diabetic hyperglycemic rabbits. The results illustrated significant antihyperglycemic activity of crude extract with 17.44% and 28.02% amelioration at 25 and 50mg/kg p.o. respectively after 24th day of drug treatment; equally supported by body weight recovery. Upon fractionation, most dominant antihyperglycemic effect was displayed by aqueous fraction with 22.12% and 34.43% effect followed by ethyl acetate fraction with 24.32% and 32.05% effect at 25 and 50mg/kg p.o. respectively after 24th day of drug treatment. The effect on blood glucose was also reflected on body weight of animals. In conclusion, our study documented marked antihyperglycemic activity of extract/fractions of P. duthiei.

Gastrointestinal Hormones and Bariatric Surgery-induced Weight Loss

PubMed Central

Ionut, Viorica; Burch, Miguel; Youdim, Adrienne; Bergman, Richard N.

2015-01-01

Obesity continues to be a major public health problem in the United States and worldwide. While recent statistics have demonstrated that obesity rates have begun to plateau, more severe classes of obesity are accelerating at a faster pace with important implications in regards to treatment. Bariatric surgery has a profound and durable effect on weight loss, being to date one of the most successful interventions for obesity. Objective To provide updates to the possible role of gut hormones in post bariatric surgery weight loss and weight loss maintenance. Design and Methods The current review examines the changes in gastro-intestinal hormones with bariatric surgery and the potential mechanisms by which these changes could result in decreased weight and adiposity. Results The mechanism by which bariatric surgery results in body weight changes is incompletely elucidated, but it clearly goes beyond caloric restriction and malabsorption. Conclusion Changes in gastro-intestinal hormones, including increases in GLP-1, PYY, and oxyntomodulin, decreases in GIP and ghrelin, or the combined action of all these hormones might play a role in induction and long-term maintenance of weight loss. PMID:23512841

Zonisamide-induced weight loss in schizophrenia: case series.

PubMed

Yang, Jaewon; Lee, Moon-Soo; Joe, Sook-Haeng; Jung, In-Kwa; Kim, Seung-Hyun

2010-01-01

Weight gain and metabolic disturbances constitute bothersome problems in schizophrenic patients treated with atypical antipsychotics. Several medications, exercise regimens, and lifestyle changes have been used in attempts to ameliorate these problems. We describe 3 patients with schizophrenia who manifested distinct weight loss and reduction in waist circumference during medication with zonisamide. This report suggests that zonisamide might be associated with weight loss in patients with schizophrenia.

Peripherally administered baclofen reduced food intake and body weight in db/db as well as diet-induced obese mice.

PubMed

Sato, Ikuko; Arima, Hiroshi; Ozaki, Noriyuki; Ozaki, Nobuaki; Watanabe, Minemori; Goto, Motomitsu; Shimizu, Hiroshi; Hayashi, Masayuki; Banno, Ryouichi; Nagasaki, Hiroshi; Oiso, Yutaka

2007-10-16

Peripheral administration of baclofen significantly reduced food intake and body weight increase in both diabetic (db/db) and diet-induced obese mice for 5 weeks, whereas it had no significant effects on energy balance in their lean control mice. Despite the decreased body weight, neuropeptide Y expression in the arcuate nucleus was significantly decreased, whereas pro-opiomelanocortin expression was significantly increased by baclofen treatment. These data demonstrate that the inhibitory effects of baclofen on body weight in the obese mice were mediated via the arcuate nucleus at least partially, and suggest that GABA(B) agonists could be a new therapeutic reagent for obesity.

Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss.

PubMed

Wicki, Simone; Gurzeler, Ursina; Corazza, Nadia; Genitsch, Vera; Wong, Wendy Wei-Lynn; Kaufmann, Thomas

2018-02-28

Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID.

Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss

PubMed Central

Wicki, Simone; Gurzeler, Ursina; Corazza, Nadia; Genitsch, Vera

2018-01-01

Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID. PMID:29495595

Protein diets, body weight loss and weight maintenance.

PubMed

Martens, Eveline A P; Westerterp-Plantenga, Margriet S

2014-01-01

The review addresses briefly the relevance of protein diets for body weight loss and weight maintenance. The addition of recent findings on age-dependent protein requirements, specific effects of protein intake and protein source, the relevance of the other dietary macronutrients, especially of 'low-carb', 'protein leverage', the mechanisms of protein-induced satiety, and food-reward makes the review up-to-date. Different effects of protein diets in different age groups result from age-dependent protein requirements that are primarily related to effects on body composition. A protein intake of 0.8 g/kg/day is sufficient to sustain a negative energy balance in adults, irrespective of the protein source. 'Low-carb' diets trace back to the protein-induced effects. Evidence that protein intake drives energy intake as suggested by the 'Protein leverage hypothesis' is scarce and equivocal. Finally, limited protein-induced food reward may affect compliance to a protein diet. An implication of the findings for clinical practice is that a protein intake of 0.8-1.2 g/kg/day is sufficient to sustain satiety, energy expenditure, and fat-free mass, independent of a dietary 'low-carb' content. Limited protein-induced food reward may affect compliance to a protein diet.

Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner.

PubMed

Bolton, Jessica L; Smith, Susan H; Huff, Nicole C; Gilmour, M Ian; Foster, W Michael; Auten, Richard L; Bilbo, Staci D

2012-11-01

Emerging evidence suggests environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal air pollution exposure would predispose the offspring to weight gain in adulthood. Pregnant mice were exposed to filtered air (FA) or diesel exhaust (DE) on embryonic days (E) 9-17. Prenatal DE induced a significant fetal brain cytokine response at E18 (46-390% over FA). As adults, offspring were fed either a low-fat diet (LFD) or high-fat diet (HFD) for 6 wk. Adult DE male offspring weighed 12% more and were 35% less active than FA male offspring at baseline, whereas there were no differences in females. Following HFD, DE males gained weight at the same rate as FA males, whereas DE females gained 340% more weight than FA females. DE-HFD males had 450% higher endpoint insulin levels than FA-HFD males, and all males on HFD showed decreased activity and increased anxiety, whereas females showed no differences. Finally, both DE males and females fed HFD showed increased microglial activation (30-66%) within several brain regions. Thus, prenatal air pollution exposure can "program" offspring for increased susceptibility to diet-induced weight gain and neuroinflammation in adulthood in a sex-specific manner.

Effect of daily short-duration weight-bearing on disuse-induced deterioration of musculoskeletal system

PubMed Central

Leung, K-S.; Li, Y-H.; Liu, Y.; Wang, H.; Tam, K-F.; Chow, D.H.K.; Wan, Y.; Ling, S.; Dai, Z.; Qin, L.; Cheung, W-H.

2015-01-01

Objectives: To investigate deterioration of musculoskeletal system due to prolonged disuse and the potential of daily short-duration weight-bearing as countermeasures. Methods: Twenty-four adult male Sprague-Dawley rats were divided into Control Group (CG, no intervention), Tail-suspension Group (TG, tail-suspension without treatment), and Weight-Bearing Group (WBG, tail-suspension with 20 min/day, 5 days/week body weight loading). After four weeks of treatment, femur and tibia, soleus and extensor digitorum longus were evaluated for bone and muscle quality respectively. Tensile properties of bone-tendon insertion (BTI) were evaluated using patella-patellar tendon complex. Results: Disuse induced deterioration on bone, muscle, and BTI after four weeks. Compared with CG, TG and WBG showed significant decrease in bone mineral density (BMD) of trabecular bone in distal femur (4.3-15.2%), muscle mass (31.3-52.3%), muscle cross-sectional area (29.1-35%), and failure strength of BTI (23.9-29.4%). Tensile test showed that the failure mode was avulsion of bone at the BTI. No significant difference was detected between TG and WBG for all assessments on bone, muscle, and BTI. Conclusions: Disuse caused deterioration of bone, muscle, and BTI while daily short-duration of weight-bearing did not prevent this deterioration. Mechanical stimulation with higher intensity and longer duration may be necessary to prevent musculoskeletal deterioration resulted from prolonged disuse. PMID:26032214

Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*

PubMed Central

Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

2016-01-01

Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. PMID:26953343

Pyrrolidin-2-one derivatives may reduce body weight in rats with diet-induced obesity.

PubMed

Dudek, Magdalena; Knutelska, Joanna; Bednarski, Marek; Nowiński, Leszek; Zygmunt, Małgorzata; Kazek, Grzegorz; Mordyl, Barbara; Głuch-Lutwin, Monika; Zaręba, Paula; Kulig, Katarzyna; Sapa, Jacek

2016-04-05

Obesity affects an increasing number of individuals in the human population and significant importance is attached to research leading to the discovery of drug which would effectively reduce weight. The search for new drugs with anorectic activity and acting within the adrenergic system has attracted the interest of researchers. This study concerns the experimental effects on body weight of α2-adrenoceptor antagonists from the group of pyrrolidin-2-one derivatives in rats with diet-induced obesity. The intrinsic activity of the test compounds at the α-adrenoreceptors was tested. Obesity in rats was obtained by the use of fatty diet and then the influence of the test compounds on body weight, food and water intakes, lipid and glucose profiles and glycerol and cortisol levels were determinated. The effects of the compounds on locomotor activity, body temperature, blood pressure and heart rate were tested. One of the test compounds (1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one) reduces the animal's body weight and the amount of peritoneal adipose tissue during chronic administration, at the same time it does not cause significant adverse effects on the cardiovascular system. This compound decreases temperature and elevates glycerol levels and does not change the locomotor activity and cortisol level at anti-obese dose. Some derivatives of pyrrolidin-2-one that act as antagonists of the α2-adrenoreceptor may reduce body weight. Reducing body weight for 1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one can be associated with decrease in food intake, body fat reduction, reduction of blood glucose, and increased thermogenesis and lipolysis. This effect cannot be the result of changes in spontaneous activity or stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Associations among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss.

PubMed

Labouesse, Marie A; Gertz, Erik R; Piccolo, Brian D; Souza, Elaine C; Schuster, Gertrud U; Witbracht, Megan G; Woodhouse, Leslie R; Adams, Sean H; Keim, Nancy L; Van Loan, Marta D

2014-07-01

Weight loss reduces co-morbidities of obesity, but decreases bone mass. Our aims were to (1) determine if adequate dairy intake attenuates weight loss-induced bone loss; (2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; and (3) model the contribution of these variables to post weight-loss BMD and BMC. Overweight/obese women (BMI: 28-37 kg/m2) were enrolled in an energy reduced (-500 kcal/d; -2092 kJ/d) diet with adequate dairy (AD: 3-4 servings/d; n=25, 32.2±8.8 years) or low dairy (LD: ≤1 serving/d; n=26, 31.7±8.4 years). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. Following weight loss, AD intake resulted in significantly greater (p=0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post-body fat was negatively associated with hip and lumbar spine BMC (r=-0.28, p=0.04 to -0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = -0.29 (p=0.04) to r = -0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss factors. Pre-weight loss factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the factors contributed to the variance in lumbar spine BMD. AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone

PDGF-BB induces vascular smooth muscle cell expression of high molecular weight FGF-2, which accumulates in the nucleus.

PubMed

Pintucci, Giuseppe; Yu, Pey-Jen; Saponara, Fiorella; Kadian-Dodov, Daniella L; Galloway, Aubrey C; Mignatti, Paolo

2005-08-15

Basic fibroblast growth factor (FGF-2) and platelet-derived growth factor (PDGF) are implicated in vascular remodeling secondary to injury. Both growth factors control vascular endothelial and smooth muscle cell proliferation, migration, and survival through overlapping intracellular signaling pathways. In vascular smooth muscle cells PDGF-BB induces FGF-2 expression. However, the effect of PDGF on the different forms of FGF-2 has not been elucidated. Here, we report that treatment of vascular aortic smooth muscle cells with PDGF-BB rapidly induces expression of 20.5 and 21 kDa, high molecular weight (HMW) FGF-2 that accumulates in the nucleus and nucleolus. Conversely, PDGF treatment has little or no effect on 18 kDa, low-molecular weight FGF-2 expression. PDGF-BB-induced upregulation of HMW FGF-2 expression is controlled by sustained activation of extracellular signal-regulated kinase (ERK)-1/2 and is abolished by actinomycin D. These data describe a novel interaction between PDGF-BB and FGF-2, and indicate that the nuclear forms of FGF-2 may mediate the effect of PDGF activity on vascular smooth muscle cells.

Effect of surfactants on weight gain in mice.

PubMed

Kaneene, J B; Ross, R W

1986-03-01

A study was conducted to determine if four surfactants can induce increased weight gain in the mouse. Basic-H, Triton X-100, Amway All Purpose Adjuvant and X-77 were put in water and fed to various groups of ICR 21 day old female mice for a period of 43 days. All the mice were clinically normal throughout the study period. Pathological examination of a random sample of the mice revealed no gross pathological changes. Similarly, histopathological examination of the lungs, livers and intestines did not reveal any visible lesions. Basic-H and Amway surfactants induced weight gain, though not significantly, better at 0.1% (V/V) concentration while X-77 and Triton X-100 induced weight gain better at 0.4% (V/V) concentration. Overall results show that none of the surfactants tested induced significant weight gain.

A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women.

PubMed

Villalon, Karen L; Gozansky, Wendolyn S; Van Pelt, Rachael E; Wolfe, Pam; Jankowski, Catherine M; Schwartz, Robert S; Kohrt, Wendy M

2011-12-01

Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1-year follow-up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6-month exercise-based weight loss program and returned for follow-up at 18 months. Dual-energy X-ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m(2). They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow-up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (-1.7 ± 3.5%; P = 0.002) and hip (-0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C-terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (-0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: -3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone-deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.

Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

USDA-ARS?s Scientific Manuscript database

We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from ...

Early prediction of olanzapine-induced weight gain for schizophrenia patients.

PubMed

Lin, Ching-Hua; Lin, Shih-Chi; Huang, Yu-Hui; Wang, Fu-Chiang; Huang, Chun-Jen

2018-05-01

The aim of this study was to determine whether weight changes at week 2 or other factors predicted weight gain at week 6 for schizophrenia patients receiving olanzapine. This study was the secondary analysis of a six-week trial for 94 patients receiving olanzapine (5 mg/d) plus trifluoperazine (5 mg/d), or olanzapine (10 mg/d) alone. Patients were included in analysis only if they had completed the 6-week trial (per protocol analysis). Weight gain was defined as a 7% or greater increase of the patient's baseline weight. The receiver operating characteristic curve was employed to determine the optimal cutoff points of statistically significant predictors. Eleven of the 67 patients completing the 6-week trial were classified as weight gainers. Weight change at week 2 was the statistically significant predictor for ultimate weight gain at week 6. A weight change of 1.0 kg at week 2 appeared to be the optimal cutoff point, with a sensitivity of 0.92, a specificity of 0.75, and an AUC of 0.85. Using weight change at week 2 to predict weight gain at week 6 is favorable in terms of both specificity and sensitivity. Weight change of 1.0 kg or more at 2 weeks is a reliable predictor. Copyright © 2018 Elsevier B.V. All rights reserved.

Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

PubMed

Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

2016-04-22

Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A role for hypothalamic AMP-activated protein kinase in the mediation of hyperphagia and weight gain induced by chronic treatment with olanzapine in female rats.

PubMed

Sejima, Ei; Yamauchi, Atsushi; Nishioku, Tsuyoshi; Koga, Mitsuhisa; Nakagama, Kengo; Dohgu, Shinya; Futagami, Kojiro; Kataoka, Yasufumi

2011-10-01

Olanzapine is known to be advantageous with respect to outcome and drug compliance in patients with schizophrenia. However, olanzapine has adverse effects, including a higher incidence of weight gain and metabolic disturbances, when compared with those of other antipsychotic agents. The mechanisms underlying these adverse events remain obscure. Female rats were orally administered olanzapine (2 mg/kg) or vehicle once a day for 2 weeks to ascertain if hypothalamic AMP-activated protein kinase (AMPK) mediates olanzapine-induced weight gain and hyperphagia. Body weight and food intake in each rat were evaluated every day and every two days, respectively. After the termination of drug treatment, we measured the protein levels of AMPK and phosphorylated AMPK in the hypothalamus using western blot analyses. Olanzapine significantly increased body weight and food intake. The phosphorylation levels of AMPK were significantly elevated by olanzapine. These results suggest that activation of hypothalamic AMPK may mediate hyperphagia and weight gain induced by chronic treatment with olanzapine.

Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells.

PubMed

Ruud, Johan; Wilhelms, Daniel Björk; Nilsson, Anna; Eskilsson, Anna; Tang, Yan-Juan; Ströhle, Peter; Caesar, Robert; Schwaninger, Markus; Wunderlich, Thomas; Bäckhed, Fredrik; Engblom, David; Blomqvist, Anders

2013-05-01

Loss of appetite is a hallmark of inflammatory diseases. The underlying mechanisms remain undefined, but it is known that myeloid differentiation primary response gene 88 (MyD88), an adaptor protein critical for Toll-like and IL-1 receptor family signaling, is involved. Here we addressed the question of determining in which cells the MyD88 signaling that results in anorexia development occurs by using chimeric mice and animals with cell-specific deletions. We found that MyD88-knockout mice, which are resistant to bacterial lipopolysaccharide (LPS)-induced anorexia, displayed anorexia when transplanted with wild-type bone marrow cells. Furthermore, mice with a targeted deletion of MyD88 in hematopoietic or myeloid cells were largely protected against LPS-induced anorexia and displayed attenuated weight loss, whereas mice with MyD88 deletion in hepatocytes or in neural cells or the cerebrovascular endothelium developed anorexia and weight loss of similar magnitude as wild-type mice. Furthermore, in a model for cancer-induced anorexia-cachexia, deletion of MyD88 in hematopoietic cells attenuated the anorexia and protected against body weight loss. These findings demonstrate that MyD88-dependent signaling within the brain is not required for eliciting inflammation-induced anorexia. Instead, we identify MyD88 signaling in hematopoietic/myeloid cells as a critical component for acute inflammatory-driven anorexia, as well as for chronic anorexia and weight loss associated with malignant disease.

Preserving Healthy Muscle during Weight Loss123

PubMed Central

Cava, Edda; Yeat, Nai Chien; Mittendorfer, Bettina

2017-01-01

Weight loss is the cornerstone of therapy for people with obesity because it can ameliorate or completely resolve the metabolic risk factors for diabetes, coronary artery disease, and obesity-associated cancers. The potential health benefits of diet-induced weight loss are thought to be compromised by the weight-loss–associated loss of lean body mass, which could increase the risk of sarcopenia (low muscle mass and impaired muscle function). The objective of this review is to provide an overview of what is known about weight-loss–induced muscle loss and its implications for overall physical function (e.g., ability to lift items, walk, and climb stairs). The currently available data in the literature show the following: 1) compared with persons with normal weight, those with obesity have more muscle mass but poor muscle quality; 2) diet-induced weight loss reduces muscle mass without adversely affecting muscle strength; 3) weight loss improves global physical function, most likely because of reduced fat mass; 4) high protein intake helps preserve lean body and muscle mass during weight loss but does not improve muscle strength and could have adverse effects on metabolic function; 5) both endurance- and resistance-type exercise help preserve muscle mass during weight loss, and resistance-type exercise also improves muscle strength. We therefore conclude that weight-loss therapy, including a hypocaloric diet with adequate (but not excessive) protein intake and increased physical activity (particularly resistance-type exercise), should be promoted to maintain muscle mass and improve muscle strength and physical function in persons with obesity. PMID:28507015

Impact of Korean pine nut oil on weight gain and immune responses in high-fat diet-induced obese mice

PubMed Central

Park, Soyoung; Lim, Yeseo; Shin, Sunhye

2013-01-01

Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-γ, and LPS-stimulated production of IL-6, IL-1β, and prostaglandin E2 (PGE2) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-1β (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-γ, IL-6, or PGE2 in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses. PMID:24133613

A novel GIP analogue, ZP4165, enhances glucagon-like peptide-1-induced body weight loss and improves glycaemic control in rodents.

PubMed

Nørregaard, Pia K; Deryabina, Maria A; Tofteng Shelton, Pernille; Fog, Jacob U; Daugaard, Jens R; Eriksson, Per-Olof; Larsen, Lone F; Jessen, Lene

2018-01-01

To investigate the effects of the novel glucose-dependent insulinotropic polypeptide (GIP) analogue, ZP4165, on body weight and glycaemic control in rodents, and to investigate if ZP4165 modulates the anti-obesity and anti-hyperglycaemic effects of a glucagon-like peptide-1 (GLP-1) agonist (liraglutide). The acute insulinotropic effect of ZP4165 was investigated in rats during an oral glucose tolerance test. The long-term effects of ZP4165 on body weight and glycaemic control, either alone or in combination with liraglutide, were assessed in diet-induced obese mice and diabetic db/db mice. ZP4165 showed insulinotropic action in rats. The GIP analogue did not alter the body weight of obese mice but enhanced GLP-1-induced weight loss. In diabetic mice, 4 weeks' dosing with ZP4165 reduced glycated haemoglobin levels vs vehicle by an extent similar to the GLP-1 agonist. ZP4165 potentiated the anti-obesity effect of a GLP-1 agonist in obese mice and improved glycaemic control in diabetic mice. These studies support further investigation of dual-incretin therapy as a more effective treatment option than mono GLP-1 medication for type 2 diabetes mellitus and obesity. © 2017 John Wiley & Sons Ltd.

Dietary and body weight control: therapeutic education, motivational interviewing and cognitive-behavioral approaches for long-term weight loss maintenance.

PubMed

Golay, Alain

2006-01-01

A diet always induces weight loss in the short term. The loss does not depend on the dietary composition but rather on the caloric deficit. However, a drastic diet often induces binge eating disorders and can lead to a weight gain in the long term. A cognitive-behavioral-nutritional approach allows lasting weight loss and best results with low fat diets in the long term. Therapeutic education is a patient-centered humanistic approach which allows patients to be actors in their own treatment and own diet to improve their success in losing weight and their quality of life. Motivational interviewing and cognitive-behavioral approaches are perfect complements to therapeutic education for long-term weight loss maintenance. Finally, the best diet is the one that the patient can follow in the long term.

Attitudes to body weight, weight gain and eating behavior in pregnancy.

PubMed

Abraham, S; King, W; Llewellyn-Jones, D

1994-12-01

The eating behavior and attitudes to body weight of 100 healthy women were studied 3 days after the birth of their first child. During pregnancy women 'watch their weight' and use a range of methods of weight control which include cigarette smoking and inducing vomiting. During pregnancy 41 women reported weight control problems and 20 women considered their weight and eating problems to be greater than at any previous time. Picking was the most common unwanted behavior. Binge eating was experienced by 44 women, nine of whom reported it to be a 'severe' problem. Although women were ambivalent about being weighed at each antenatal visit, 81 recommended weighing once each month. The women held differing opinions on the effects of breastfeeding on body weight and on the need for nutritional supplements during pregnancy. Women reporting 'disordered eating' were more likely to have antenatal complications and give birth to low birthweight babies. The results suggest good obstetric care should include a history of the woman's eating behavior and body weight.

Vitamins A and E reverse gasoline vapors-induced hematotoxicity and weight loss in female rats.

PubMed

Uboh, F E; Eteng, M U; Ebong, P E; Umoh, I B

2010-10-01

In this study, gasoline vapors-induced hematotoxicity, growth-depression and weight-loss reversal effect of vitamins A (retinol) and E (α-tocopherol) was assessed in female Wistar albino rats. The rats were exposed to gasoline vapors (17.8 ± 2.6 cm(3)/h/m(3)/day), 6 hours/day, 6 days/week, for 20 weeks. Vitamins A and E at prophylactic dosage (400 and 200 IU/kg/day, respectively) were orally administered to the rats, separately, in the last 2 weeks of exposure. The levels of hemoglobin (Hb), hematocrit or packed cell volume (PCV), red blood cells (RBC), growth rate and weight gain in the rats exposed to the vapors were significantly lower (p < 0.05) compared, respectively, to the levels obtained for control rats. On the other hand, the levels of white blood cells (WBCs) in the test rats were significantly higher (p < 0.05) compared, respectively, with the level obtained for female control rats. These observations indicated that exposure to gasoline vapors may cause hematotoxicity, growth depression and weight loss in female rats. However, administration of vitamins A and E was observed to produce a significant recovery (p < 0.05) in hematotoxicity, growth depression and weight loss observed to be associated with exposure to gasoline vapors, although the rats administered with vitamin E were noted to respond more favorably than those administered with vitamin A. This suggests that although retinol and α-tocopherol may be used to reverse or prevent hematotoxicity, growth depression and weight loss in subjects exposed to gasoline vapors, the reversal potency of α-tocopherol is higher than that of retinol.

Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.

PubMed

Velázquez, Kandy T; Enos, Reilly T; Carson, Meredith S; Cranford, Taryn L; Bader, Jackie E; Chatzistamou, Ioulia; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi; Davis, J Mark; Carson, James A; Murphy, E Angela

2016-10-01

Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80 + CD206 + macrophages and activated T cells (CD4 + CD69 + ) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms. Copyright © 2016 the American Physiological Society.

High fat diet-induced metabolically obese and normal weight rabbit model shows early vascular dysfunction: mechanisms involved.

PubMed

Alarcon, Gabriela; Roco, Julieta; Medina, Mirta; Medina, Analia; Peral, Maria; Jerez, Susana

2018-01-30

Obesity contributes significantly to the development and evolution of cardiovascular disease (CVD) which is believed to be mediated by oxidative stress, inflammation and endothelial dysfunction. However, the vascular health of metabolically obese and normal weight (MONW) individuals is not completely comprehended. The purpose of our study was to evaluate vascular function on the basis of a high fat diet (HFD)-MONW rabbit model. Twenty four male rabbits were randomly assigned to receive either a regular diet (CD, n = 12) or a high-fat diet (18% extra fat on the regular diet, HFD, n = 12) for 6 weeks. Body weight, TBARS and gluthathione serum levels were similar between the groups; fasting glucose, triglycerides, C reactive protein (CRP), visceral adipose tissue (VAT), triglyceride-glucose index (TyG index) were higher in the HFD group. Compared to CD, the HFD rabbits had glucose intolerance and lower HDL-cholesterol and plasma nitrites levels. Thoracic aortic rings from HFD rabbits exhibited: (a) a reduced acetylcholine-induced vasorelaxation; (b) a greater contractile response to norepinephrine and KCl; (c) an improved angiotensin II-sensibility. The HFD-effect on acetylcholine-response was reversed by the cyclooxygenase-2 (COX-2) inhibitor (NS398) and the cyclooxygenase-1 inhibitor (SC560), and the HFD-effect on angiotensin II was reversed by NS398 and the TP receptor blocker (SQ29538). Immunohistochemistry and western blot studies showed COX-2 expression only in arteries from HFD rabbits. Our study shows a positive pro-inflammatory status of HFD-induced MONW characterized by raised COX-2 expression, increase of the CRP levels, reduction of NO release and oxidative stress-controlled conditions in an early stage of metabolic alterations characteristic of metabolic syndrome. Endothelial dysfunction and increased vascular reactivity in MONW individuals may be biomarkers of early vascular injury. Therefore, the metabolic changes induced by HFD even in normal

Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent of changes in body weight in female mice

PubMed Central

Winn, Nathan C.; Gastecki, Michelle L.; Welly, Rebecca J.; Scroggins, Rebecca J.; Zidon, Terese M.; Gaines, T’Keaya L.; Woodford, Makenzie L.; Karasseva, Natalia G.; Kanaley, Jill A.; Sacks, Harold S.

2017-01-01

We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1) would have increased susceptibility to Western diet-induced “whitening” of brown adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1−/−) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass. Despite similar susceptibility to weight gain compared with WT, UCP1−/− exhibited whitening of brown AT evidenced by a striking ~500% increase in mass and appearance of large unilocular adipocytes, increased expression of genes related to inflammation, immune cell infiltration, and endoplasmic reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by Western diet (P < 0.05). UCP1−/− mice also developed liver steatosis and glucose intolerance, which was worsened by Western diet. Collectively, these findings demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown AT, glucose intolerance, and induces liver steatosis. Notably, the adverse metabolic manifestations of UCP1−/− were independent of changes in body weight, visceral adiposity, and energy expenditure. These novel findings uncover a previously unrecognized metabolic protective role of UCP1 that is independent of its already established role in energy homeostasis. PMID:27881400

Zingiber mioga reduces weight gain, insulin resistance and hepatic gluconeogenesis in diet-induced obese mice

PubMed Central

LEE, DA-HYE; AHN, JIYUN; JANG, YOUNG JIN; HA, TAE-YOUL; JUNG, CHANG HWA

2016-01-01

Zingiber mioga is a perennial herb belonging to the ginger family (Zingiberaceae) that is used medicinally to treat cough and rheumatism in China and consumed throughout Japan. The aim of the present study was to investigate the anti-obesity effects of Z. mioga following extraction with distilled water or 70% ethanol. In 3T3-L1 preadipocyte cells, Z. mioga water extract (ZMW) markedly inhibited adipogenesis, whereas the ethanol extract had no effect. In addition, we conducted ZMW feeding experiments (0.25 or 0.5% ZMW) in high-fat diet (HFD)-fed mice to examine the anti-obesity effects of Z. mioga in vivo. Body weight and serum triglyceride and cholesterol levels significantly decreased in the HFD + ZMW 0.5% group. Notably, ZMW decreased liver weight but not adipose tissue weight. Furthermore, insulin resistance and hepatic mRNA expression of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and G6Pase, were improved in the HFD + ZMW 0.5% group. Furthermore, ZMW treatment decreased hepatic lipogenic gene expression; however, it did not alter adipogenesis in fat tissue, suggesting that ZMW inhibits hepatosteatosis through the suppression of lipogenesis. ZMW improved HFD-induced hepatic inflammation. Collectively, the present findings suggest that ZMW may serve as a new and promising strategy for the treatment of hepatosteatosis. PMID:27347064

Effects of Visfatin Gene Polymorphism RS4730153 on Exercise-induced Weight Loss of Obese Children and Adolescents of Han Chinese

PubMed Central

Lai, Aiping; Chen, Wenhe; Helm, Kelly

2013-01-01

Visfatin is a recently discovered adipokine that contributes to glucose and obesity-related conditions. This study investigates Visfatin RS4730153 polymorphism from the perspectives of its relations with glucose/lipid metabolism and its influence on the effects of exercise-induced weight loss. Eighty-eight obese Han Chinese children and adolescents were randomly selected from a 2008 Shanghai Weight Loss Summer Camp and were supervised to complete a 4 week aerobic exercise training program. Significant differences were observed in before-exercise TG value and exercise-induced HOMA-β change, with the AG group having a much higher TG value than the GG group (P ≤ 0.05), and the latter exhibiting a significantly larger before-and-after exercise HOMA-β change than the former (P ≤ 0.05). However, no significant difference was observed between the two groups in before exercise indices of body shape, function and quality, nor in exercise-induced changes of body shape, function, and quality. Findings suggest that Visfatin RS4730153 homozygous GG genotype may effect adjustment of glucose and lipid metabolism in obese children and adolescents by reducing TG levels and increasing insulin sensitivity to exercise. PMID:23289013

Theory of interaction-induced renormalization of Drude weight and plasmon frequency in chiral multilayer graphene

NASA Astrophysics Data System (ADS)

Li, Xiao; Tse, Wang-Kong

2017-02-01

We develop a theory for the optical conductivity of doped ABC-stacked multilayer graphene including the effects of electron-electron interactions. Applying the quantum kinetic formalism, we formulate a set of pseudospin Bloch equations that govern the dynamics of the nonequilibrium density matrix driven by an external ac electric field under the influence of Coulomb interactions. These equations reveal a dynamical mechanism that couples the Drude and interband responses arising from the chirality of pseudospin textures in multilayer graphene systems. We demonstrate that this results in an interaction-induced enhancement of the Drude weight and plasmon frequency strongly dependent on the pseudospin winding number. Using bilayer graphene as an example, we also study the influence of higher-energy bands and find that they contribute considerable renormalization effects not captured by a low-energy two-band description. We argue that this enhancement of Drude weight and plasmon frequency occurs generally in materials characterized by electronic chirality.

Numerical Simulation of Unsteady Turbulent Flow Induced by Two-Dimensional Elevator Car and Counter Weight System

NASA Astrophysics Data System (ADS)

Shi, Li-qun; Liu, Ying-zheng; Jin, Si-yu; Cao, Zhao-min

2007-12-01

A two-dimensional model of unsteady turbulent flow induced by high-speed elevator system was established in the present study. The research was focused on the instantaneous variation of the aerodynamic force on the car structure during traversing motion of the counter weight in the hoistway. A dynamic meshing method was employed to treat the multi-body motion system to avoid poor distortion of meshes. A comprehensive understanding of this significant aspect was obtained by varying the horizontal gap (Δ = 0.1m, 0.2m, and 0.3m) between the elevator car and the counter weight, and the moving speed ( U 0 = 2m/s, 6m/s, and 10m/s) of the elevator system. A pulsed intensification of the aerodynamic force on the elevator car and subsequent appearance of large valley with negative aerodynamic force were clearly observed in the numerical results. In parameters studied (Δ = 0.1m, U 0 = 2m/s, 6m/s, 10m/s), the peaked horizontal and vertical forces are respectively 7-11 and 4.3-5.65 times of that when the counter weight is far from the car. These results demonstrated the prominent influence of the traversing counter weight on aerodynamic force on the elevator car, which is of great significance to designers of high-speed elevator system.

Peptide Fragmentation by Corona Discharge Induced Electrochemical Ionization

PubMed Central

Lloyd, John R.; Hess, Sonja

2010-01-01

Fundamental studies have greatly improved our understanding of electrospray, including the underlying electrochemical reactions. Generally regarded as disadvantageous, we have recently shown that corona discharge (CD) can be used as an effective method to create a radical cation species [M]+•, thus optimizing the electrochemical reactions that occur on the surface of the stainless steel (SS) electrospray capillary tip. This technique is known as CD initiated electrochemical ionization (CD-ECI). Here, we report on the fundamental studies using CD-ECI to induce analytically useful in-source fragmentation of a range of molecules that complex transition metals. Compounds that have been selectively fragmented using CD-ECI include enolate forming phenylglycine containing peptides, glycopeptides, nucleosides and phosphopeptides. Collision induced dissociation (CID) or other activation techniques were not necessary for CD-ECI fragmentation. A four step mechanism was proposed: 1. Complexation using either Fe in the SS capillary tip material or Cu(II) as an offline complexation reagent; 2. Electrochemical oxidation of the complexed metal and thus formation of a radical cation (e.g.; Fe - e− → Fe +•); 3. Radical fragmentation of the complexed compound. 4. Electrospray ionization of the fragmented neutrals. Fragmentation patterns resembling b- and y-type ions were observed and allowed the localization of the phosphorylation sites. PMID:20869880

Pharmacogenetics of clozapine response and induced weight gain: A comprehensive review and meta-analysis.

PubMed

Gressier, Florence; Porcelli, Stefano; Calati, Raffaella; Serretti, Alessandro

2016-02-01

Clozapine (CLZ) is the prototype atypical antipsychotic and it has many advantages over other antipsychotic drugs. Several data suggest that both CLZ response and induced weight gain are strongly determined by genetic variability. However, results remain mainly inconclusive. We aim to review the literature data about pharmacogenetics studies on CLZ efficacy, focusing on pharmacodynamic genes. Further, we performed meta-analyses on response when at least three studies for each polymorphism were available. Sensitivity analyses were conducted on Caucasian population when feasible. Electronic literature search was performed to identify pertinent studies published until May 2014 using PubMed, ISI Web of Knowledge and PsycINFO databases. For meta-analyses, data were entered and analyzed through RevMan version 5.2 using a random-effect model. Our literature search yielded 9266 articles on CLZ; among these, we identified 59 pertinent pharmacogenetic studies. Genotype data were retrieved for 14 polymorphisms in 9 genes. Among these, we had available data from at least three independent samples for 8 SNPs in 6 genes to perform meta-analyses: DRD2 rs1799732, DRD3 rs6280, HTR2A rs6313, rs6311, rs6314, HTR2C rs6318, HTR3A rs1062613, TNFa rs1800629. Although literature review provided conflicting results, in meta-analyses three genetic variants within serotonin genes resulted associated to CLZ response: rs6313 and rs6314 within HTR2A gene and rs1062613 within HT3A gene. On the other hand, no clear finding emerged for CLZ-induced weight gain. Our results suggest a possible serotonergic modulation of CLZ clinical response. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Three Months of High-Fructose Feeding Fails to Induce Excessive Weight Gain or Leptin Resistance in Mice

PubMed Central

Tillman, Erik J.; Morgan, Donald A.; Rahmouni, Kamal; Swoap, Steven J.

2014-01-01

High-fructose diets have been implicated in obesity via impairment of leptin signaling in humans and rodents. We investigated whether fructose-induced leptin resistance in mice could be used to study the metabolic consequences of fructose consumption in humans, particularly in children and adolescents. Male C57Bl/6 mice were weaned to a randomly assigned diet: high fructose, high sucrose, high fat, or control (sugar-free, low-fat). Mice were maintained on their diets for at least 14 weeks. While fructose-fed mice regularly consumed more kcal and expended more energy, there was no difference in body weight compared to control by the end of the study. Additionally, after 14 weeks, both fructose-fed and control mice displayed similar leptin sensitivity. Fructose-feeding also did not change circulating glucose, triglycerides, or free fatty acids. Though fructose has been linked to obesity in several animal models, our data fail to support a role for fructose intake through food lasting 3 months in altering of body weight and leptin signaling in mice. The lack of impact of fructose in the food of growing mice on either body weight or leptin sensitivity over this time frame was surprising, and important information for researchers interested in fructose and body weight regulation. PMID:25211467

Lack of weight gain after angiotensin AT1 receptor blockade in diet-induced obesity is partly mediated by an angiotensin-(1–7)/ Mas-dependent pathway

PubMed Central

Schuchard, Johanna; Winkler, Martina; Stölting, Ines; Schuster, Franziska; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Santos, Robson A; Bader, Michael; Raasch, Walter

2015-01-01

Background and Purpose Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II. As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascular and metabolic effects. Experimental Approach We investigated the anti-obesity effects of transgenically overexpressed angiotensin-(1-7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg·kg−1·d−1) in diet-induced obese Sprague Dawley (SD) rats can be blocked when the animals were co-treated with the Mas receptor antagonist A779 (24 or 72 μg·kg−1·d−1). Key Results In contrast to wild-type controls, transgenic rats overexpressing angiotensin-(1-7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain-dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan-induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779. Conclusions and Implications Angiotensin-(1-7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin-(1-7)-like agonists may be drug candidates for treating obesity. PMID:25906670

Gestational Weight Gain and Post-Partum Weight Loss Among Young, Low-Income, Ethnic Minority Women

PubMed Central

ROTHBERG, Bonnie E. Gould; MAGRIPLES, Urania; KERSHAW, Trace S.; RISING, Sharon Schindler; ICKOVICS, Jeannette R.

2010-01-01

Objective Document weight change trajectories that lead to gestational weight gain or postpartum weight loss outside clinical recommendations established by Institute of Medicine (IOM). Methods Women aged 14-25 receiving prenatal care and delivering singleton infants at term (N=427). Medical record review and four structured interviews conducted: second and third trimester, 6- and 12-months postpartum. Longitudinal mixed modeling to evaluate weight change trajectories. Results Only 22% of participants gained gestational weight within IOM guidelines. 62% exceeded maximum recommendations -- more common among those overweight/obese (BMI≥25.0; p<0.0001). 52% retained ≥10 pounds one-year postpartum. Increased weight gain and retention documented among smokers and women with pregnancy-induced hypertension; breastfeeding promoted postpartum weight loss (all p<.02). BMI by race interaction suggested healthier outcomes for Latinas (p=0.02). Conclusion Excessive pregnancy weight gain and inadequate postpartum weight loss are highly prevalent among young low-income ethnic minority women. Pregnancy and postpartum are critical junctures for weight management interventions. PMID:20974459

Dairy Food Consumption and Meal-Induced Cortisol Response Interacted to Influence Weight Loss in Overweight Women Undergoing a 12-Week, Meal-Controlled, Weight Loss Intervention1234

PubMed Central

Witbracht, Megan G.; Van Loan, Marta; Adams, Sean H.; Keim, Nancy L.; Laugero, Kevin D.

2013-01-01

Dairy food enhances weight loss in animal models, possibly by modifying the metabolic effects of cortisol. This study determined in overweight women (ages 20.0–45.9 y; n = 51) whether including dairy food in an energy-restricted diet affects cortisol concentrations and whether differences in provoked cortisol explain the magnitude of weight loss. Women received either an adequate amount of dairy food (AD), the equivalent of ≥711 mL/d milk, or a low amount of dairy food (LD), the equivalent to ≤238 mL/d milk, in a 12-wk, energy-restricted dietary intervention. Participants were tested in a 12-h laboratory visit, which included 2 standard meals and a dinner buffet that was consumed ad libitum. Salivary cortisol was measured from waking to bedtime. Energy restriction increased (P ≤ 0.04) the minimum and decreased (P ≤ 0.02) the diurnal amplitude in the salivary cortisol concentration from baseline to postintervention. Energy restriction enhanced the dinner meal–stimulated salivary cortisol response (DMR) (P ≤ 0.02) but only in the LD group. Compared with the LD treatment, the AD treatment induced (P ≤ 0.04) greater reductions in body weight and fat, but only in women characterized as having a baseline DMR (responders) (n = 26); weight and fat lost in the AD and LD groups were similar in nonresponders (n = 25). Overall, energy restriction dampened diurnal salivary cortisol fluctuations [symptomatic of hypothalamic-pituitary-adrenal (HPA) axis dysfunction] and enhanced dinner meal–stimulated salivary cortisol concentrations. The AD treatment prevented the latter. Furthermore, certain phenotypic markers of HPA axis function may help to expose the weight-reducing effects of consuming dairy food. PMID:23190756

Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin.

PubMed

Trcka, Jiri; Seitz, Cornelia S; Bröcker, Eva-B; Gross, Gerd E; Trautmann, Axel

2007-07-01

Aminopenicillin-induced exanthema poses a problem in the management of infectious diseases. Due to theoretically possible immunological cross-reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing bacterial resistance to antibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-induced exanthema may receive specific beta-lactams for future antibiotic therapy. Skin testing followed by oral challenges to identify beta-lactams that are tolerated by patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to aminopenicillins. Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin. The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to determine individual cross-reactivity.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task.

PubMed

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. © 2015 S. Karger GmbH, Freiburg.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

PubMed Central

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

Objective It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. PMID:26139105

Weight Loss Nutritional Supplements

NASA Astrophysics Data System (ADS)

Eckerson, Joan M.

Obesity has reached what may be considered epidemic proportions in the United States, not only for adults but for children. Because of the medical implications and health care costs associated with obesity, as well as the negative social and psychological impacts, many individuals turn to nonprescription nutritional weight loss supplements hoping for a quick fix, and the weight loss industry has responded by offering a variety of products that generates billions of dollars each year in sales. Most nutritional weight loss supplements are purported to work by increasing energy expenditure, modulating carbohydrate or fat metabolism, increasing satiety, inducing diuresis, or blocking fat absorption. To review the literally hundreds of nutritional weight loss supplements available on the market today is well beyond the scope of this chapter. Therefore, several of the most commonly used supplements were selected for critical review, and practical recommendations are provided based on the findings of well controlled, randomized clinical trials that examined their efficacy. In most cases, the nutritional supplements reviewed either elicited no meaningful effect or resulted in changes in body weight and composition that are similar to what occurs through a restricted diet and exercise program. Although there is some evidence to suggest that herbal forms of ephedrine, such as ma huang, combined with caffeine or caffeine and aspirin (i.e., ECA stack) is effective for inducing moderate weight loss in overweight adults, because of the recent ban on ephedra manufacturers must now use ephedra-free ingredients, such as bitter orange, which do not appear to be as effective. The dietary fiber, glucomannan, also appears to hold some promise as a possible treatment for weight loss, but other related forms of dietary fiber, including guar gum and psyllium, are ineffective.

Ketosis and appetite-mediating nutrients and hormones after weight loss.

PubMed

Sumithran, P; Prendergast, L A; Delbridge, E; Purcell, K; Shulkes, A; Kriketos, A; Proietto, J

2013-07-01

Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss. Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding. During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding. The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.

Decaffeinated green and black tea polyphenols decrease weight gain and alter microbiome populations and function in diet-induced obese mice.

PubMed

Henning, Susanne M; Yang, Jieping; Hsu, Mark; Lee, Ru-Po; Grojean, Emma M; Ly, Austin; Tseng, Chi-Hong; Heber, David; Li, Zhaoping

2017-09-30

Decaffeinated green tea (GT) and black tea (BT) polyphenols inhibit weight gain in mice fed an obesogenic diet. Since the intestinal microflora is an important contributor to obesity, it was the objective of this study to determine whether the intestinal microflora plays a role in the anti-obesogenic effect of GT and BT. C57BL/6J mice were fed a high-fat/high-sucrose diet (HF/HS, 32% energy from fat; 25% energy from sucrose) or the same diet supplemented with 0.25% GTP or BTP or a low-fat/high-sucrose (LF/HS, 10.6% energy from fat, 25% energy from sucrose) diet for 4 weeks. Bacterial composition was assessed by MiSeq sequencing of the 16S rRNA gene. GTP and BTP diets resulted in a decrease of cecum Firmicutes and increase in Bacteroidetes. The relative proportions of Blautia, Bryantella, Collinsella, Lactobacillus, Marvinbryantia, Turicibacter, Barnesiella, and Parabacteroides were significantly correlated with weight loss induced by tea extracts. BTP increased the relative proportion of Pseudobutyrivibrio and intestinal formation of short-chain fatty acids (SCFA) analyzed by gas chromatography. Cecum propionic acid content was significantly correlated with the relative proportion of Pseudobutyrivibrio. GTP and BTP induced a significant increase in hepatic 5'adenosylmonophosphate-activated protein kinase (AMPK) phosphorylation by 70 and 289%, respectively (P < 0.05) determined by Western blot. In summary, both BTP and GTP induced weight loss in association with alteration of the microbiota and increased hepatic AMPK phosphorylation. We hypothesize that BTP increased pAMPK through increased intestinal SCFA production, while GTPs increased hepatic AMPK through GTP present in the liver.

Genetics of antipsychotic-induced weight gain: update and current perspectives.

PubMed

Kao, Amy C C; Müller, Daniel J

2013-12-01

Antipsychotic medications are used to effectively treat various symptoms for different psychiatric conditions. Unfortunately, antipsychotic-induced weight gain (AIWG) is a common side effect that frequently results in obesity and secondary medical conditions. Twin and sibling studies have indicated that genetic factors are likely to be highly involved in AIWG. Over recent years, there has been considerable progress in this area, with several consistently replicated findings, as well as the identification of new genes and implicated pathways. Here, we will review the most recent genetic studies related to AIWG using the Medline database (PubMed) and Google Scholar. Among the steadiest findings associated with AIWG are serotonin 2C receptors (HTR2C) and leptin promoter gene variants, with more recent studies implicating MTHFR and, in particular, MC4R genes. Additional support was reported for the HRH1, BDNF, NPY, CNR1, GHRL, FTO and AMPK genes. Notably, some of the reported variants appear to have relatively large effect sizes. These findings have provided insights into the mechanisms involved in AIWG and will help to develop predictive genetic tests in the near future.

Experiences with three different fiber supplements in weight reduction.

PubMed

Birketvedt, Grethe Støa; Shimshi, Mona; Erling, Thom; Florholmen, Jon

2005-01-01

Fiber supplements added to a caloric diet have additional effects on weight reduction in overweight subjects. The aim of this study was to compare the effect of various commercial fiber supplements (glucomannan, guar gum and alginate) on weight reduction in healthy overweight subjects. One hundred and seventy six men and women were included to receive either active fiber substance or placebo in randomized placebo-controlled studies. The fiber supplements consisted of the viscous fibers glucomannan (Chrombalance), glucomannan and guar gum (Appe-Trim) and glucomannan, guar gum and alginat (Glucosahl). All fiber supplements plus a balanced 1200 kcal diet induced significantly weight reduction more than placebo and diet alone, during a five week observation period. However, there were no significant differences between the different fibers in their ability to induce weight reduction, which was approximately 0.8 kg/week (3.8 +/- 0.9, 4.4 +/- 2.0, 4.1 +/- 0.6 in the Chrombalance, Appe-Trim and Glucosahl group, respectively). Glucomannan induced body weight reduction in healthy overweight subjects, whereas the addition of guar gum and alginate did not seem to cause additional loss of weight.

Left ventricular mass in elite olympic weight lifters.

PubMed

Lalande, Sophie; Baldi, James Christopher

2007-10-01

The existence of resistance training-induced left ventricular (LV) concentric hypertrophy is equivocal. Although some have described significant LV hypertrophy, others have suggested that training-induced LV hypertrophy is proportional to increased fat free mass (FFM) and thus a normal physiologic response to training. Method limitations, steroid use, and type of training may contribute to discrepant findings. Thus, LV structure and volumes are determined using magnetic resonance imaging. Body composition was determined using dual-energy x-ray absorptiometry in 9 elite Olympic weight lifters and 10 age- and weight-matched recreationally active controls. LV structure and volumes were determined by acquiring 6 short- and 3 long-axis magnetic resonance imaging scans of the left ventricle, whereas LV wall thickness was defined as the average of 6 midventricular segment thickness measurements. Weight lifters had the same age, weight, and FFM, but were shorter and had a greater body mass index than controls. LV mass was not different in weight lifters and controls, but was lower in weight lifters when indexed to FFM (2.56 +/- 0.07 vs 2.30 +/- 0.05, p = 0.01). LV mass correlated with FFM (r = 0.49, p = 0.04). However, LV mass was lower in weight lifters for a given FFM. LV wall thickness, as well as end-diastolic, end-systolic, and stroke volumes, were not different between groups. In conclusion, these results refute the hypothesis that resistance training induces LV concentric hypertrophy and suggest that Olympic weight lifting is associated with increases in FFM without a concomitant increase in LV mass.

Gestational weight gain and subsequent postpartum weight loss among young, low-income, ethnic minority women.

PubMed

Gould Rothberg, Bonnie E; Magriples, Urania; Kershaw, Trace S; Rising, Sharon Schindler; Ickovics, Jeannette R

2011-01-01

Document weight change trajectories that lead to gestational weight gain or postpartum weight loss outside clinical recommendations established by the Institute of Medicine. Women aged 14-25 receiving prenatal care and delivering singleton infants at term (n = 427). Medical record review and 4 structured interviews conducted: second and third trimester, 6- and 12-months postpartum. Longitudinal mixed modeling to evaluate weight change trajectories. Only 22% of participants gained gestational weight within Institute of Medicine guidelines. There were 62% that exceeded maximum recommendations-more common among those overweight/obese (body mass index ≥25.0; P < .0001). 52% retained ≥10 lb 1-year postpartum. Increased weight gain and retention documented among smokers and women with pregnancy-induced hypertension; breastfeeding promoted postpartum weight loss (all P < .02). Body mass index by race interaction suggested healthier outcomes for Latinas (P = .02). Excessive pregnancy weight gain and inadequate postpartum weight loss are highly prevalent among young low-income ethnic minority women. Pregnancy and postpartum are critical junctures for weight management interventions. Copyright © 2011 Mosby, Inc. All rights reserved.

Small Molecular Weight Soybean Protein-Derived Peptides Nutriment Attenuates Rat Burn Injury-Induced Muscle Atrophy by Modulation of Ubiquitin-Proteasome System and Autophagy Signaling Pathway.

PubMed

Zhao, Fen; Yu, Yonghui; Liu, Wei; Zhang, Jian; Liu, Xinqi; Liu, Lingying; Yin, Huinan

2018-03-21

This article describes results of the effect of dietary supplementation with small molecular weight soybean protein-derived peptides on major rat burn injury-induced muscle atrophy. As protein nutrients have been previously implicated to play an important role in improving burn injury outcomes, optimized more readily absorbed small molecular weight soybean protein-derived peptides were evaluated. Thus, the quantity, sodium dodecyl sulfate polyacrylamide-gel electrophoresis patterns, molecular weight distribution, and composition of amino acids of the prepared peptides were analyzed, and a major full-thickness 30% total body surface area burn-injury rat model was utilized to assess the impact of supplementation with soybean protein-derived peptides on initial systemic inflammatory responses as measured by interferon-gamma (IFN-γ), chemokine (C-C motif) ligand 2 (CCL2, also known as MCP-1), chemokine (C-C motif) ligand 7 (CCL7, also known as MCP-3), and generation of muscle atrophy as measured by tibialis anterior muscle (TAM) weight relative to total body weight. Induction of burn injury-induced muscle atrophy ubiquitin-proteasome system (UPS) signaling pathways in effected muscle tissues was determined by Western blot protein expression measurements of E3 ubiquitin-protein ligase TRIM-63 (TRIM63, also known as MuRF1) and F-box only protein 32 (FBXO32, also known as atrogin-1 or MAFbx). In addition, induction of burn injury-induced autophagy signaling pathways associated with muscle atrophy in effected muscle tissues was assessed by immunohistochemical analysis as measured by microtubule-associated proteins 1 light chain 3 (MAP1LC3, or commonly abbreviated as LC3) and beclin-1 (BECN1) expression, as well as relative induction of cytoplasmic-liberated form of MAP1LC3 (LC3-I) and phagophore and autophagosome membrane-bound form of MAP1LC3 (LC3-II), and BECN1 protein expression by Western blot analysis. Nutrient supplementation with small molecular weight soybean

Induced Autolysis of Aspergillus oryzae (A. niger group)

PubMed Central

Emiliani, Ezio; de Davie, I. Ucha

1962-01-01

The examination of substances formed during induced autolysis by Aspergillus niger was continued in this work, which dealt in particular with carbohydrates. The autolysate contained a large amount of d-glucose (14 to 20% dry wt) and traces of glycolic aldehyde, dihydroxyacetone, ribose, xylose, and fructose. It also contained glycopeptides (about 10% dry wt), which were split from the cell wall during autolysis and which differed from one another in their level of polymerization and their composition. They were constituted by glucose and mannose, glucose and galactose, or mannose, glucose, and galactose (mannose being the most abundant in this case), and amino acids (chiefly alanine, serine, glutamic acid, and aspartic acid). During autolysis, only a part of the cell wall was dissolved, since it retained its shape. Upon further chemical hydrolysis, it produced mostly glucose and glucosamine, and smaller amounts of mannose, galactose, and amino acids. Presumably, glucomannoproteins and glucogalactoproteins were present in the intact cell as a macromolecular complex, constituting, together with chitin, the major part of the cell wall of Aspergillus. PMID:16349623

Adaptive changes in pancreas post Roux-en-Y gastric bypass induced weight loss.

PubMed

Lautenbach, A; Wernecke, M; Riedel, N; Veigel, J; Yamamura, J; Keller, S; Jung, R; Busch, P; Mann, O; Knop, F K; Holst, J J; Meier, J J; Aberle, J

2018-05-16

Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known, whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following RYGB. Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. 11 patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf. Before and 6 months after RYGB, total GLP-1 levels were measured during OGTT. To assess changes in visceral adipose tissue and pancreatic volume, MRI was performed. Measures of glucose homeostasis and insulin indices were assessed. Fractional beta-cell area was estimated by correlation with the C-peptide-to-glucose ratio, beta-cell mass was calculated by the product of beta-cell area and pancreas parenchymal weight. Pancreas volume decreased from 83.8 (75.7-92.0) to 70.5 (58.8-82.3) cm 3 [mean (95% CI), p=0.001]. The decrease in total volume was associated with a significant decrease in fat volume. Fasting insulin and C-peptide were lower post RYGB. HOMA-IR levels decreased, whereas insulin sensitivity increased (p=0.03). This was consistent with a reduction in the estimated beta-cell area and mass. Following RYGB, pancreatic volume and steatosis adaptively decreased to "normal" levels with accompanying improvement in glucose homeostasis. Moreover, obesity-driven beta-cell expansion seems to be reversible, however future studies must define a method to more accurately estimate functional beta-cell mass to increase our understanding of glucose homeostasis after RYGB. This article is protected by copyright. All rights reserved.

Factor for adipocyte differentiation 158 gene disruption prevents the body weight gain and insulin resistance induced by a high-fat diet.

PubMed

Hayashi, Takahiro; Nozaki, Yuriko; Nishizuka, Makoto; Ikawa, Masahito; Osada, Shigehiro; Imagawa, Masayoshi

2011-01-01

To clarify the molecular mechanism of adipocyte differentiation, we previously isolated a novel gene, factor for adipocyte differentiation (fad) 158, whose expression was induced during the earliest stages of adipogenesis, and its product was localized to the endoplasmic reticulum. We found that the knockdown of fad158 expression prevented the differentiation of 3T3-L1 cells into adipocytes. In addition, over-expression of fad158 promoted the differentiation of NIH-3T3 cells, which do not usually differentiate into adipocytes. Although these findings strongly suggest that fad158 has a crucial role in regulating adipocyte differentiation, the physiological role of the gene is still unclear. In this study, we generated mice in which fad158 expression was deleted. The fad158-deficient mice did not show remarkable changes in body weight or the weight of white adipose tissue on a chow diet, but had significantly lower body weights and fat mass than wild-type mice when fed a high-fat diet. Furthermore, although the disruption of fad158 did not influence insulin sensitivity on the chow diet, it improved insulin resistance induced by the high-fat diet. These results indicate that fad158 is a key factor in the development of obesity and insulin resistance caused by a high-fat diet.

PSF mapping-based correction of eddy-current-induced distortions in diffusion-weighted echo-planar imaging.

PubMed

In, Myung-Ho; Posnansky, Oleg; Speck, Oliver

2016-05-01

To accurately correct diffusion-encoding direction-dependent eddy-current-induced geometric distortions in diffusion-weighted echo-planar imaging (DW-EPI) and to minimize the calibration time at 7 Tesla (T). A point spread function (PSF) mapping based eddy-current calibration method is newly presented to determine eddy-current-induced geometric distortions even including nonlinear eddy-current effects within the readout acquisition window. To evaluate the temporal stability of eddy-current maps, calibration was performed four times within 3 months. Furthermore, spatial variations of measured eddy-current maps versus their linear superposition were investigated to enable correction in DW-EPIs with arbitrary diffusion directions without direct calibration. For comparison, an image-based eddy-current correction method was additionally applied. Finally, this method was combined with a PSF-based susceptibility-induced distortion correction approach proposed previously to correct both susceptibility and eddy-current-induced distortions in DW-EPIs. Very fast eddy-current calibration in a three-dimensional volume is possible with the proposed method. The measured eddy-current maps are very stable over time and very similar maps can be obtained by linear superposition of principal-axes eddy-current maps. High resolution in vivo brain results demonstrate that the proposed method allows more efficient eddy-current correction than the image-based method. The combination of both PSF-based approaches allows distortion-free images, which permit reliable analysis in diffusion tensor imaging applications at 7T. © 2015 Wiley Periodicals, Inc.

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934.

PubMed

Ulrich, Veronika; Brieke, Clara; Cryle, Max J

2016-01-01

The chemical complexity and biological activity of the glycopeptide antibiotics (GPAs) stems from their unique crosslinked structure, which is generated by the actions of cytochrome P450 (Oxy) enzymes that affect the crosslinking of aromatic side chains of amino acid residues contained within the GPA heptapeptide precursor. Given the crucial role peptide cyclisation plays in GPA activity, the characterisation of this process is of great importance in understanding the biosynthesis of these important antibiotics. Here, we report the cyclisation activity and crystal structure of StaF, the D- O -E ring forming Oxy enzyme from A47934 biosynthesis. Our results show that the specificity of StaF is reduced when compared to Oxy enzymes catalysing C- O -D ring formation and that this activity relies on interactions with the non-ribosomal peptide synthetase via the X-domain. Despite the interaction of StaF with the A47934 X-domain being weaker than for the preceding Oxy enzyme StaH, StaF retains higher levels of in vitro activity: we postulate that this is due to the ability of the StaF/X-domain complex to allow substrate reorganisation after initial complex formation has occurred. These results highlight the importance of testing different peptide/protein carrier constructs for in vitro GPA cyclisation assays and show that different Oxy homologues can display significantly different catalytic propensities despite their overall similarities.

Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats

PubMed Central

Deblon, N; Bourgoin, L; Veyrat-Durebex, C; Peyrou, M; Vinciguerra, M; Caillon, A; Maeder, C; Fournier, M; Montet, X; Rohner-Jeanrenaud, F; Foti, M

2012-01-01

BACKGROUND AND PURPOSE mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti-cancer agents. However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms associated with the diabetogenic effects of chronic Sirolimus administration in rats and in in vitro cell cultures. EXPERIMENTAL APPROACH Sirolimus was administered to rats fed either a standard or high-fat diet for 21 days. Metabolic parameters were measured in vivo and in ex vivo tissues. Insulin sensitivity was assessed by glucose tolerance tests and euglycaemic hyperinsulinaemic clamps. Rapamycin effects on glucose metabolism and insulin signalling were further evaluated in cultured myotubes. KEY RESULTS Sirolimus induced a decrease in food intake and concomitant weight loss. It also induced specific fat mass loss that was independent of changes in food intake. Despite these beneficial effects, Sirolimus-treated rats were glucose intolerant, hyperinsulinaemic and hyperglycaemic, but not hyperlipidaemic. The euglycaemic hyperinsulinaemic clamp measurements showed skeletal muscle is a major site of Sirolimus-induced insulin resistance. At the molecular level, long-term Sirolimus administration attenuated glucose uptake and metabolism in skeletal muscle by preventing full insulin-induced Akt activation and altering the expression and translocation of glucose transporters to the plasma membrane. In rats fed a high-fat diet, these metabolic defects were exacerbated, although Sirolimus-treated animals were protected from diet-induced obesity. CONCLUSIONS AND IMPLICATIONS Taken together, our data demonstrate that the diabetogenic effect of chronic rapamycin administration is due to an impaired insulin action on glucose metabolism in skeletal muscles. PMID:22014210

Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats.

PubMed

Deblon, N; Bourgoin, L; Veyrat-Durebex, C; Peyrou, M; Vinciguerra, M; Caillon, A; Maeder, C; Fournier, M; Montet, X; Rohner-Jeanrenaud, F; Foti, M

2012-04-01

mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti-cancer agents. However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms associated with the diabetogenic effects of chronic Sirolimus administration in rats and in in vitro cell cultures. Sirolimus was administered to rats fed either a standard or high-fat diet for 21 days. Metabolic parameters were measured in vivo and in ex vivo tissues. Insulin sensitivity was assessed by glucose tolerance tests and euglycaemic hyperinsulinaemic clamps. Rapamycin effects on glucose metabolism and insulin signalling were further evaluated in cultured myotubes. Sirolimus induced a decrease in food intake and concomitant weight loss. It also induced specific fat mass loss that was independent of changes in food intake. Despite these beneficial effects, Sirolimus-treated rats were glucose intolerant, hyperinsulinaemic and hyperglycaemic, but not hyperlipidaemic. The euglycaemic hyperinsulinaemic clamp measurements showed skeletal muscle is a major site of Sirolimus-induced insulin resistance. At the molecular level, long-term Sirolimus administration attenuated glucose uptake and metabolism in skeletal muscle by preventing full insulin-induced Akt activation and altering the expression and translocation of glucose transporters to the plasma membrane. In rats fed a high-fat diet, these metabolic defects were exacerbated, although Sirolimus-treated animals were protected from diet-induced obesity. Taken together, our data demonstrate that the diabetogenic effect of chronic rapamycin administration is due to an impaired insulin action on glucose metabolism in skeletal muscles. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Effects of 8 Weeks of Balance or Weight Training for the Independently Living Elderly on the Outcomes of Induced Slips

ERIC Educational Resources Information Center

Kim, Sukwon; Lockhart, Thurmon

2010-01-01

The study was conducted to evaluate whether the balance or weight training could alter gait characteristics of elderly contributing to a reduction in the likelihood of slip-induced falls. A total of 18 elderly were evaluated for the study. The results indicated decreases in heel contact velocities and the friction demand characteristics after 8…

A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia.

PubMed

Kim, Eosu; Park, Dong-Wha; Choi, Song-Hee; Kim, Jae-Jin; Cho, Hyun-Sang

2008-04-01

Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that alpha-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain. We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study. These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.

Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial.

PubMed

Liu, G; Liang, L; Bray, G A; Qi, L; Hu, F B; Rood, J; Sacks, F M; Sun, Q

2017-06-01

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (P trend =0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (P trend =0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin

Thyroid Hormones and Changes in Body Weight and Metabolic Parameters in Response to Weight-Loss Diets: The POUNDS LOST Trial

PubMed Central

Liu, Gang; Liang, Liming; Bray, George A.; Qi, Lu; Hu, Frank B.; Rood, Jennifer; Sacks, Frank M.; Sun, Qi

2017-01-01

Background The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. Objectives To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. Subjects/Methods Data analysis was conducted among 569 overweight and obese participants aged 30–70 years with normal thyroid function participating in the 2-year POUNDS LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine [T3], free thyroxine [T4], total T3, total T4, and thyroid stimulating hormone [TSH]), anthropometric measurements, and biochemical parameters were assessed at baseline, 6 months, and 24 months. Results Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6–24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index, and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss ± standard error was −3.87±0.9 vs −5.39±0.9 kg for free T3 (P trend=0.02) and −4.09±0.9 vs −5.88±0.9 kg for free T4 (P trend=0.004). The thyroid hormones did not predict weight regain in 6–24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides

Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study.

PubMed

Wu, Ren-Rong; Jin, Hua; Gao, Keming; Twamley, Elizabeth W; Ou, Jian-Jun; Shao, Ping; Wang, Juan; Guo, Xiao-Feng; Davis, John M; Chan, Philip K; Zhao, Jing-Ping

2012-08-01

Data on the treatment of antipsychotic-induced amenorrhea, particularly when occurring with weight gain, are limited. The authors investigated the efficacy and safety of metformin in the treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia. Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months. The primary outcome measures were restoration of menstruation and change in body weight and body mass index (BMI). Secondary outcome measures were changes in levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone; in fasting levels of insulin and glucose; in LH/FSH ratio; and in insulin resistance index. Repeated mixed models with repeated-measures regression analyses and binary logistic regression were used in the analysis. A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group. Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.

Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat.

PubMed

Hunt, Hazel J; Ray, Nicholas C; Hynd, George; Sutton, Jon; Sajad, Mohammed; O'Connor, Elizabeth; Ahmed, Shahadat; Lockey, Peter; Daly, Steve; Buckley, Gerry; Clark, Robin D; Roe, Robert; Blasey, Christine; Belanoff, Joe

2012-12-15

We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

Associations among Endocrine, Inflammatory, and Bone Markers, Body Composition and Physical Activity to Weight Loss Induced Bone Loss

PubMed Central

Labouesse, Marie A.; Gertz, Erik R.; Piccolo, Brian D.; Souza, Elaine C.; Schuster, Gertrud U.; Witbracht, Megan G.; Woodhouse, Leslie R.; Adams, Sean H.; Keim, Nancy L.; Van Loan, Marta D.

2015-01-01

INTRODUCTION Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE Our aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; 3) model the contribution of these variables to post weight-loss BMD and BMC METHODS Overweight/obese women (BMI: 28–37 kg/m2) were enrolled in an energy reduced (−500 kcal/d; −2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n=25, 32.2 ± 8.8y) or low dairy (LD: ≤ 1 serving/d; n=26, 31.7 ± 8.4 y). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS Following weight loss, AD intake resulted in significantly greater (p= 0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post- body fat were negatively associated with hip and lumbar spine BMC (r= −0.28, p=0.04 to −0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = −0.29 (p=0.04) to r = −0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss Factors. Pre-weight loss Factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss Factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the Factors contributed to the variance in lumbar spine BMD. CONCLUSION AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD

Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss

PubMed Central

Weiss, Edward P.; Racette, Susan B.; Villareal, Dennis T.; Fontana, Luigi; Steger-May, Karen; Schechtman, Kenneth B.; Klein, Samuel; Ehsani, Ali A.; Holloszy, John O.

2015-01-01

Caloric restriction (CR) results in fat loss; however, it may also result in loss of muscle and thereby reduce strength and aerobic capacity (V̇O2 max). These effects may not occur with exercise-induced weight loss (EX) because of the anabolic effects of exercise on heart and skeletal muscle. We tested the hypothesis that CR reduces muscle size and strength and V̇O2 max, whereas EX preserves or improves these parameters. Healthy 50- to 60-yr-old men and women (body mass index of 23.5–29.9 kg/m2) were studied before and after 12 mo of weight loss by CR (n = 18) or EX (n = 16). Lean mass was assessed by dual-energy X-ray absorptiometry, thigh muscle volume by MRI, isometric and isokinetic knee flexor strength by dynamometry, and treadmill V̇O2 max by indirect calorimetry. Both interventions caused significant decreases in body weight (CR: −10.7 ± 1.4%, EX: −9.5 ± 1.5%) and lean mass (CR: −3.5 ± 0.7%, EX: −2.2 ± 0.8%), with no significant differences between groups. Significant decreases in thigh muscle volume (−6.9 ± 0.8%) and composite knee flexion strength (−7.2 ± 3%) occurred in the CR group only. Absolute V̇O2 max decreased significantly in the CR group (−6.8 ± 2.3%), whereas the EX group had significant increases in both absolute (+15.5 ± 2.4%) and relative (+28.3 ± 3.0%) V̇O2 max. These data provide evidence that muscle mass and absolute physical work capacity decrease in response to 12 mo of CR but not in response to a similar weight loss induced by exercise. These findings suggest that, during EX, the body adapts to maintain or even enhance physical performance capacity. PMID:17095635

Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip BMD induced by weight loss despite decline in bone-active hormones*

PubMed Central

Shah, Krupa; Armamento-Villareal, Reina; Parimi, Nehu; Chode, Suresh; Sinacore, David R.; Hilton, Tiffany N.; Napoli, Nicola; Qualls, Clifford; Villareal, Dennis T.

2011-01-01

Weight-loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight-loss therapy should include an intervention to minimize bone loss such as exercise training (ET). The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 yrs) obese (BMI ≥30 kg/m2) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (−9.6%) and diet-exercise (−9.4%) groups, not in the exercise (−1%) and control (−0.2%) groups (between-group P<.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (−1.1%) than in the diet group (−2.6%), whereas BMD increased in the exercise group (1.5%) (between-group P<.001) Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%) while they decreased in the exercise group (−13% and −15%) (between-group P<.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (−15%) compared with the diet group (9%) (P=.04). Serum leptin and estradiol concentrations decreased in the diet (−25% and −15%) and diet-exercise (−38% and −13%) groups, not in the exercise and control groups (between-group P=.001). Multivariate analyses revealed that changes in lean body mass (β=.33), serum osteocalcin (β= −.24), and 1-RM strength (β=.23) were independent predictors of changes in hip BMD (all P<.05). In conclusion, the addition of ET to weight-loss therapy among obese older adults prevents weight-loss-induced increase in bone turnover and attenuates

Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems.

PubMed

Mukundan, Anitha; Faulkner, Guy; Cohn, Tony; Remington, Gary

2010-12-08

Weight gain is common for people with schizophrenia and this has serious implications for a patient's health and well being. Switching strategies have been recommended as a management option. To determine the effects of antipsychotic medication switching as a strategy for reducing or preventing weight gain and metabolic problems in people with schizophrenia. We searched key databases and the Cochrane Schizophrenia Group's trials register (January 2005 and June 2007), reference sections within relevant papers and contacted the first author of each relevant study and other experts to collect further information. All clinical randomised controlled trials comparing switching of antipsychotic medication as an intervention for antipsychotic induced weight gain and metabolic problems with continuation of medication and/or other weight loss treatments (pharmacological and non pharmacological) in people with schizophrenia or schizophrenia-like illnesses. Studies were reliably selected, quality assessed and data extracted. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. The primary outcome measures were weight loss, metabolic syndrome, relapse and general mental state. We included four studies for the review with a total of 636 participants. All except one study had a duration of 26 weeks or less. There was a mean weight loss of 1.94 kg (2 RCT, n = 287, CI -3.9 to 0.08) when switched to aripiprazole or quetiapine from olanzapine. BMI also decreased when switched to quetiapine (1 RCT, n = 129, MD -0.52 CI -1.26 to 0.22) and aripiprazole (1 RCT, n = 173, RR 0.28 CI 0.13 to 0.57) from olanzapine.Fasting blood glucose showed a significant decrease when switched to aripiprazole or quetiapine from olanzapine. (2 RCT, MD -2.53 n = 280 CI -2.94 to -2.11). One RCT also showed a favourable lipid profile when switched to aripiprazole but these measures were reported as percentage

Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis

PubMed Central

Haddad, Oualid; Guyot, Erwan; Marinval, Nicolas; Chevalier, Fabien; Maillard, Loïc; Gadi, Latifa; Laguillier-Morizot, Christelle; Oudar, Olivier; Sutton, Angela; Charnaux, Nathalie; Hlawaty, Hanna

2015-01-01

Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases. PMID:26516869

Effects of rehydration fluid temperature and composition on body weight retention upon voluntary drinking following exercise-induced dehydration

PubMed Central

Bae, Yoon Jung; Lee, Yong Soo; Kim, Byeong Jo

2012-01-01

The purpose of this study was to determine the effects of beverage temperature and composition on weight retention and fluid balance upon voluntary drinking following exercise induced-dehydration. Eight men who were not acclimated to heat participated in four randomly ordered testing sessions. In each session, the subjects ran on a treadmill in a chamber maintained at 37℃ without being supplied fluids until 2% body weight reduction was reached. After termination of exercise, they recovered for 90 min under ambient air conditions and received one of the following four test beverages: 10℃ water (10W), 10℃ sports drink (10S), 26℃ water (26W), and 26℃ sports drink (26S). They consumed the beverages ad libitum. The volume of beverage consumed and body weight were measured at 30, 60, and 90 min post-recovery. Blood samples were taken before and immediately after exercise as well as at the end of recovery in order to measure plasma parameters and electrolyte concentrations. We found that mean body weight decreased by 1.8-2.0% following exercise. No differences in mean arterial pressure, plasma volume, plasma osmolality, and blood electrolytes were observed among the conditions. Total beverage volumes consumed were 1,164 ± 388, 1,505 ± 614, 948 ± 297, and 1,239 ± 401 ml for 10W, 10S, 26W, and 26S respectively (P > 0.05). Weight retention at the end of recovery from dehydration was highest in 10S (1.3 ± 0.7 kg) compared to 10W (0.4 ± 0.5 kg), 26W (0.4 ± 0.4 kg), and (0.6 ± 0.4 kg) (P < 0.005). Based on these results, carbohydrate/electrolyte-containing beverages at cool temperature were the most favorable for consumption and weight retention compared to plain water and moderate temperature beverages. PMID:22586501

Long-lasting improvements in liver fat and metabolism despite body weight regain after dietary weight loss.

PubMed

Haufe, Sven; Haas, Verena; Utz, Wolfgang; Birkenfeld, Andreas L; Jeran, Stephanie; Böhnke, Jana; Mähler, Anja; Luft, Friedrich C; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens; Engeli, Stefan

2013-11-01

Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known. We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17-36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance. Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline. A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions.

RYGB produces more sustained body weight loss and improvement of glycemic control compared with VSG in the diet-induced obese mouse model

PubMed Central

Hao, Zheng; Townsend, R. Leigh; Mumphrey, Michael B; Morrison, Christopher D; Münzberg, Heike; Berthoud, Hans-Rudolf

2018-01-01

Objective To compare the effects of murine models of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure, and glycemic control. Background Weight regain and type-2 diabetes relapse has been reported in a significant proportion of VSG patients in some studies, but definitive conclusions regarding the long-term comparative effectiveness of VSG and RYGB are lacking both in humans and rodent models. Methods VSG, RYGB, and sham surgery was performed in high-fat diet-induced obese mice and the effects on body weight and glycemic control were observed for a period of 12 weeks. Results After the initial weight loss, VSG mice regained significant amounts of body weight and fat mass that were only marginally lower than in sham-operated mice. In contrast, RYGB produced sustained loss of body weight and fat mass up to 12 weeks, and drastically improved fasting insulin and HOMA-IR compared with sham-operated mice. Using weight-matched control groups we also found that the adaptive hypometabolic response to weight loss was blunted by both VSG and RYGB, and that despite large weight/fat regain, fasting insulin and HOMA-IR were markedly improved, but not reversed, in VSG mice. Conclusions VSG is less effective to lastingly suppress body weight and improve glycemic control compared with RYGB in mice. Given similar observations in many human studies, the run towards replacing RYGB with VSG is premature and should await carefully controlled randomized long term trials with VSG and RYGB. PMID:28386755

RYGB Produces more Sustained Body Weight Loss and Improvement of Glycemic Control Compared with VSG in the Diet-Induced Obese Mouse Model.

PubMed

Hao, Zheng; Townsend, R Leigh; Mumphrey, Michael B; Morrison, Christopher D; Münzberg, Heike; Berthoud, Hans-Rudolf

2017-09-01

Weight regain and type-2 diabetes relapse has been reported in a significant proportion of vertical sleeve gastrectomy (VSG) patients in some studies, but definitive conclusions regarding the long-term comparative effectiveness of VSG and Roux-en-Y gastric bypass (RYGB) surgery are lacking both in humans and rodent models. This study's objective was to compare the effects of murine models of VSG and RYGB surgery on body weight, body composition, food intake, energy expenditure, and glycemic control. VSG, RYGB, and sham surgery was performed in high-fat diet-induced obese mice, and the effects on body weight and glycemic control were observed for a period of 12 weeks. After the initial weight loss, VSG mice regained significant amounts of body weight and fat mass that were only marginally lower than in sham-operated mice. In contrast, RYGB produced sustained loss of body weight and fat mass up to 12 weeks and drastically improved fasting insulin and HOMA-IR compared with sham-operated mice. Using weight-matched control groups, we also found that the adaptive hypometabolic response to weight loss was blunted by both VSG and RYGB, and that despite large weight/fat regain, fasting insulin and HOMA-IR were markedly improved, but not reversed, in VSG mice. VSG is less effective to lastingly suppress body weight and improve glycemic control compared with RYGB in mice. Given similar observations in many human studies, the run towards replacing RYGB with VSG is premature and should await carefully controlled randomized long-term trials with VSG and RYGB.

The brain renin‐angiotensin system plays a crucial role in regulating body weight in diet‐induced obesity in rats

PubMed Central

Winkler, Martina; Schuchard, Johanna; Stölting, Ines; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Bader, Michael

2016-01-01

Background and Purpose Reduced weight gain after treatment with AT1 receptor antagonists may involve a brain‐related mechanism. Here, we investigated the role of the brain renin‐angiotensin system on weight regulation and food behaviour, with or without additional treatment with telmisartan. Methods Transgenic rats with a brain‐specific deficiency in angiotensinogen (TGR(ASrAOGEN)) and the corresponding wild‐type, Sprague Dawley (SD) rats were fed (3 months) with a high‐calorie cafeteria diet (CD) or standard chow. SD and TGR(ASrAOGEN) rats on the CD diet were also treated with telmisartan (8 mg·kg−1·d−1, 3 months). Results Compared with SD rats, TGR(ASrAOGEN) rats (i) had lower weights during chow feeding, (ii) did not become obese during CD feeding, (iii) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD, (iv) showed a reduced energy intake, (v) had a higher, strain‐dependent energy expenditure, which is additionally enhanced during CD feeding, (vi) had enhanced mRNA levels of pro‐opiomelanocortin and (vii) showed improved glucose control. Weight gain and energy intake in rats fed the CD diet were markedly reduced by telmisartan in SD rats but only to a minor extent in TGR(ASrAOGEN) rats. Conclusions The brain renin‐angiotensin system affects body weight regulation, feeding behaviour and metabolic disorders. When angiotensin II levels are low in brain, rats are protected from developing diet‐induced obesity and obesity‐related metabolic impairments. We further suggest that telmisartan at least partly lowers body weight via a CNS‐driven mechanism. PMID:26892671

The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain.

PubMed

Fonseka, Trehani M; Tiwari, Arun K; Gonçalves, Vanessa F; Lieberman, Jeffrey A; Meltzer, Herbert Y; Goldstein, Benjamin I; Kennedy, James L; Kennedy, Sidney H; Müller, Daniel J

2015-01-01

Antipsychotics with high weight gain-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether variants in the genes encoding interleukin (IL)-1β, IL-2, and IL-6 and brain-derived neurotrophic factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain (AIWG). Nineteen polymorphisms were genotyped using Taqman(®) assays in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean weight change (%) from baseline was compared across genotypic groups using analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction. In European patients, IL-1β rs16944*GA (P = 0.013, Pcorrected = 0.182), IL-1β rs1143634*G (P = 0.001, Pcorrected = 0.014), and BDNF Val66Met (Val/Val, P = 0.004, Pcorrected = 0.056) were associated with greater AIWG, as were IL-1β rs4849127*A (P = 0.049, Pcorrected = 0.784), and IL-1β rs16944*GA (P = 0.012, Pcorrected = 0.192) in African Americans. BDNF Val66Met interacted with both IL-1β rs13032029 (Val/Met+ TT, PPerm = 0.029), and IL-6 rs2069837 (Val/Val+ AA, PPerm = 0.021) in Europeans, in addition to IL-1β rs16944 (Val/Val+ GA, PPerm = 0.006) in African Americans. SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.

Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat.

PubMed

Neff, Karl J; Elliott, Jessie A; Corteville, Caroline; Abegg, Kathrin; Boza, Camilo; Lutz, Thomas A; Docherty, Neil G; le Roux, Carel W

2017-01-01

Reductions in urinary protein excretion after Roux-en-Y gastric bypass (RYGB) surgery in patients with diabetic kidney disease have been reported in multiple studies. To determine the weight loss dependence of the effect of RYGB on urinary protein excretion by comparing renal outcomes in Zucker diabetic fatty rats undergoing either gastric bypass surgery or a sham operation with or without weight matching. University laboratories. Zucker diabetic fatty rats underwent surgery at 18 weeks of age. A subgroup of sham operated rats were weight matched to RYGB operated rats by restricting food intake. Urinary protein excretion was assessed at baseline and at postoperative weeks 4 and 12. Renal histology and macrophage-associated inflammation were assessed at postoperative week 12. Progressive urinary protein excretion was attenuated by both RYGB and diet-induced weight loss, albeit to a lesser extent by the latter. Both weight loss interventions produced equivalent reductions in glomerulomegaly, glomerulosclerosis, and evidence of renal macrophage infiltration. Weight loss per se improves renal structure and attenuates renal inflammatory responses in an experimental animal model of diabetic kidney disease. Better glycemic control post-RYGB may in part explain the greater reductions in urinary protein excretion after gastric bypass surgery. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Non-weight bearing-induced muscle weakness: the role of myosin quantity and quality in MHC type II fibers.

PubMed

Kim, Jong-Hee; Thompson, LaDora V

2014-07-15

We tested the hypothesis that non-weight bearing-induced muscle weakness (i.e., specific force) results from decreases in myosin protein quantity (i.e., myosin content per half-sarcomere and the ratio of myosin to actin) and quality (i.e., force per half-sarcomere and population of myosin heads in the strong-binding state during muscle contraction) in single myosin heavy chain (MHC) type II fibers. Fisher-344 rats were assigned to weight-bearing control (Con) or non-weight bearing (NWB). The NWB rats were hindlimb unloaded for 2 wk. Diameter, force, and MHC content were determined in permeabilized single fibers from the semimembranosus muscle. MHC isoform and the ratio of MHC to actin in each fiber were determined by gel electrophoresis and silver staining techniques. The structural distribution of myosin from spin-labeled fiber bundles during maximal isometric contraction was evaluated using electron paramagnetic resonance spectroscopy. Specific force (peak force per cross-sectional area) in MHC type IIB and IIXB fibers from NWB was significantly reduced by 38% and 18%, respectively. MHC content per half-sarcomere was significantly reduced by 21%. Two weeks of hindlimb unloading resulted in a reduced force per half-sarcomere of 52% and fraction of myosin strong-binding during contraction of 34%. The results suggest that reduced myosin and actin content (quantity) and myosin quality concomitantly contribute to non-weight bearing-related muscle weakness. Copyright © 2014 the American Physiological Society.

Functional characterization of a promoter polymorphism that drives ACSL5 gene expression in skeletal muscle and associates with diet-induced weight loss.

PubMed

Teng, Allen C T; Adamo, Kristi; Tesson, Frédérique; Stewart, Alexandre F R

2009-06-01

Diet-induced weight loss is affected by a wide range of factors, including genetic variation. Identifying functional polymorphisms will help to elucidate mechanisms that account for variation in dietary metabolism. Previously, we reported a strong association between a common single nucleotide polymorphism (SNP) rs2419621 (C>T) in the promoter of acyl-CoA synthetase long chain 5 (ACSL5), rapid weight loss in obese Caucasian females, and elevated ACSL5 mRNA levels in skeletal muscle biopsies. Here, we showed by electrophoretic mobility shift assay (EMSA) that the T allele creates a functional cis-regulatory E-box element (CANNTG) that is recognized by the myogenic regulatory factor MyoD. The T allele promoted MyoD-dependent activation of a 1089-base pair ACSL5 promoter fragment in nonmuscle CV1 cells. Differentiation of skeletal myoblasts significantly elevated expression of the ACSL5 promoter. The T allele sustained promoter activity 48 h after differentiation, whereas the C allele showed a significant decline. These results reveal a mechanism for elevated transcription of ACSL5 in skeletal muscle of carriers of the rs2419621(T) allele, associated with more rapid diet-induced weight loss. Natural selection favoring promoter polymorphisms that reduced expression of catabolic genes in skeletal muscle likely accounts for the resistance of obese individuals to dietary intervention.

Nutrient Intake During Diet-Induced Weight Loss and Exercise Interventions in a Randomized Trial in Older Overweight and Obese Adults.

PubMed

Miller, G D; Beavers, D P; Hamm, D; Mihalko, S L; Messier, S P

2017-01-01

Dietary restriction in obese older adults undergoing weight loss may exacerbate nutrient deficiencies common in this group; the nutritional health of older adults is a factor in their quality of life, disability, and mortality. This study examined the effect of an 18-month weight loss program based in social cognitive theory incorporating partial meal replacements, on nutrient intake in older overweight and obese adults. The following analysis is from the Intensive Diet and Exercise for Arthritis (IDEA) trial, a single-blind, randomized controlled trial. Individuals were randomized into one of three 18-month interventions: exercise (E); intensive diet-induced weight loss (D); or intensive diet-induced weight loss plus exercise (D+E). The study setting was at a university research facility. Overweight and obese older adults (n=388; BMI=33.7±3.8 kg/m2; 65.8±6.1 years) were recruited. The D and D+E interventions (group mean goal of ≥10% loss by 18-months) utilized partial meal replacements (2 meal replacement shakes/day for 6-months). Exercise training for E and D+E was 3 days/week, 60 minutes/day. Three day food records were collected at baseline, 6-months, and 18-months and analyzed for total energy and macro- and micronutrient intake. Comparisons of dietary intake among treatment groups were performed at 6 and 18 months using mixed linear models. Weight loss at 18-months was 11.3±8.3% (D), 10.3±6.8% (D+E), and 1.2±4.2% (E). Meal replacements were used by more than 60% (6-months) and 50% (18-months) of D and D+E participants, compared to ≤15% for E. Both D and D+E consumed less energy and fat, and more carbohydrates and selected micronutrients than E during follow-up. More than 50% of all participants consumed less than the recommended intake of particular vitamins and minerals. The diet intervention improved intakes of several nutrients. However, inadequate intake of several vitamins and minerals of concern for older adults suggests they need further

Robustness of weighted networks

NASA Astrophysics Data System (ADS)

Bellingeri, Michele; Cassi, Davide

2018-01-01

Complex network response to node loss is a central question in different fields of network science because node failure can cause the fragmentation of the network, thus compromising the system functioning. Previous studies considered binary networks where the intensity (weight) of the links is not accounted for, i.e. a link is either present or absent. However, in real-world networks the weights of connections, and thus their importance for network functioning, can be widely different. Here, we analyzed the response of real-world and model networks to node loss accounting for link intensity and the weighted structure of the network. We used both classic binary node properties and network functioning measure, introduced a weighted rank for node importance (node strength), and used a measure for network functioning that accounts for the weight of the links (weighted efficiency). We find that: (i) the efficiency of the attack strategies changed using binary or weighted network functioning measures, both for real-world or model networks; (ii) in some cases, removing nodes according to weighted rank produced the highest damage when functioning was measured by the weighted efficiency; (iii) adopting weighted measure for the network damage changed the efficacy of the attack strategy with respect the binary analyses. Our results show that if the weighted structure of complex networks is not taken into account, this may produce misleading models to forecast the system response to node failure, i.e. consider binary links may not unveil the real damage induced in the system. Last, once weighted measures are introduced, in order to discover the best attack strategy, it is important to analyze the network response to node loss using nodes rank accounting the intensity of the links to the node.

Single Rapamycin Administration Induces Prolonged Downward Shift in Defended Body Weight in Rats

PubMed Central

Hebert, Mark; Licursi, Maria; Jensen, Brittany; Baker, Ashley; Milway, Steve; Malsbury, Charles; Grant, Virginia L.; Adamec, Robert; Hirasawa, Michiru; Blundell, Jacqueline

2014-01-01

Manipulation of body weight set point may be an effective weight loss and maintenance strategy as the homeostatic mechanism governing energy balance remains intact even in obese conditions and counters the effort to lose weight. However, how the set point is determined is not well understood. We show that a single injection of rapamycin (RAP), an mTOR inhibitor, is sufficient to shift the set point in rats. Intraperitoneal RAP decreased food intake and daily weight gain for several days, but surprisingly, there was also a long-term reduction in body weight which lasted at least 10 weeks without additional RAP injection. These effects were not due to malaise or glucose intolerance. Two RAP administrations with a two-week interval had additive effects on body weight without desensitization and significantly reduced the white adipose tissue weight. When challenged with food deprivation, vehicle and RAP-treated rats responded with rebound hyperphagia, suggesting that RAP was not inhibiting compensatory responses to weight loss. Instead, RAP animals defended a lower body weight achieved after RAP treatment. Decreased food intake and body weight were also seen with intracerebroventricular injection of RAP, indicating that the RAP effect is at least partially mediated by the brain. In summary, we found a novel effect of RAP that maintains lower body weight by shifting the set point long-term. Thus, RAP and related compounds may be unique tools to investigate the mechanisms by which the defended level of body weight is determined; such compounds may also be used to complement weight loss strategy. PMID:24787262

Caffeine Treatment Prevented from Weight Regain after Calorie Shifting Diet Induced Weight Loss

PubMed Central

Davoodi, Sayed Hossein; Hajimiresmaiel, Seyed Javad; Ajami, Marjan; Mohseni-Bandpei, Anoushiravan; Ayatollahi, Seyyed Abdulmajid; Dowlatshahi, Kamran; Javedan, Gholamali; Pazoki-Toroudi, Hamidreza

2014-01-01

Low calorie diets are always difficult for obese subjects to follow and lead to metabolic and behavioral adaptation. Therefore, we evaluated the effect of caffeine treatment with calorie shifting diet (CSD) on weight loss. Female subjects (n=60; BMI≥25) completed 4-weeks control diet, 6-weeks CSD (3 repeated phases; each 2-weeks) and 4-weeks follow-up diet, with or without caffeine treatment (5 mg/Kg/day). The first 11 days of each phase included calorie restriction with four meals every day and 4 hours intervals. Significant weight and fat loss were observed after 4-weeks of CSD (5.7 ± 1.24 Kg and 4.84 ± 1.53 Kg) or CSD+Caffeine (7.57 ± 2.33 Kg and 5.24 ± 2.07 Kg) which was consistent for one month of the follow-up (CSD: 5.24 ± 1.83 Kg and 4.3 ± 1.62 Kg, CSD+Caffeine: 12.11 ± 2.31 Kg and 9.85 ± 1.6 Kg, p < 0.05 vs CSD group) and correlated to the restricted energy intake (p < 0.05). During three CSD phases, RMR tended to remain unchanged in both groups.While, CSD or CSD + Caffeine treatments, significantly decreased plasma glucose, total-cholesterol, and triacylglycerol (p < 0.05), even during follow-up period (p < 0.05). HDL-cholesterol was not changed by CSD. Feeling of hunger decreased and subject’s satisfaction increased after 4-weeks of CSD (p < 0.05) and remained low to the end of study, while satiety was not affected. Coffeine increased the effect of CSD on feeling of hunger and subject’s satisfaction after week 7 (p < 0.05 vs. CSD). These findings indicated that combination of caffeine treatment with CSD could be an effective alternative approach to weight and fat loss with small changes in RMR and improved tolerance of subjects to the new diet. PMID:25237367

Long-Lasting Improvements in Liver Fat and Metabolism Despite Body Weight Regain After Dietary Weight Loss

PubMed Central

Haufe, Sven; Haas, Verena; Utz, Wolfgang; Birkenfeld, Andreas L.; Jeran, Stephanie; Böhnke, Jana; Mähler, Anja; Luft, Friedrich C.; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens; Engeli, Stefan

2013-01-01

OBJECTIVE Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known. RESEARCH DESIGN AND METHODS We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17–36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance. RESULTS Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline. CONCLUSIONS A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions. PMID:23963894

Consumption of clarified grapefruit juice ameliorates high-fat diet induced insulin resistance and weight gain in mice.

PubMed

Chudnovskiy, Rostislav; Thompson, Airlia; Tharp, Kevin; Hellerstein, Marc; Napoli, Joseph L; Stahl, Andreas

2014-01-01

To determine the metabolic effects of grapefruit juice consumption we established a model in which C57Bl/6 mice drank 25-50% sweetened GFJ, clarified of larger insoluble particles by centrifugation (cGFJ), ad libitum as their sole source of liquid or isocaloric and sweetened water. cGFJ and control groups consumed similar amounts of liquids and calories. Mice fed a high-fat diet and cGFJ experienced a 18.4% decrease in weight, a 13-17% decrease in fasting blood glucose, a three-fold decrease in fasting serum insulin, and a 38% decrease in liver triacylglycerol values, compared to controls. Mice fed a low-fat diet that drank cGFJ experienced a two-fold decrease in fasting insulin, but not the other outcomes observed with the high-fat diet. cGFJ consumption decreased blood glucose to a similar extent as the commonly used anti-diabetic drug metformin. Introduction of cGFJ after onset of diet-induced obesity also reduced weight and blood glucose. A bioactive compound in cGFJ, naringin, reduced blood glucose and improved insulin tolerance, but did not ameliorate weight gain. These data from a well-controlled animal study indicate that GFJ contains more than one health-promoting neutraceutical, and warrant further studies of GFJ effects in the context of obesity and/or the western diet.

Effectiveness of honey on radiation-induced oral mucositis, time to mucositis, weight loss, and treatment interruptions among patients with head and neck malignancies: A meta-analysis and systematic review of literature.

PubMed

Co, Jayson L; Mejia, Michael Benedict A; Que, Jocelyn C; Dizon, Janine Margarita R

2016-07-01

Mucositis is a disabling effect of radiotherapy in head and neck cancers. There is no current standard on management of radiation-induced mucositis. Honey has been shown to reduce radiation-induced mucositis. A systematic review and meta-analysis were undertaken to assess the ability of honey in reducing the severity of oral mucositis, time to mucositis, weight loss, and treatment interruptions. Eight studies were included and showed that honey was significantly better in lowering the risk for treatment interruptions, weight loss, and delaying time to mucositis, but not severity of mucositis. There is current evidence that honey is beneficial for patients with head and neck cancers by decreasing treatment interruptions, weight loss, and delaying the onset of oral mucositis, but not in decreasing peak mucositis score. In light of the results, honey is a reasonable treatment for radiation-induced mucositis, but more randomized clinical trials (RCTs) should be done. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1119-1128, 2016. © 2016 Wiley Periodicals, Inc.

Low incidence of heparin-induced skin lesions in orthopedic surgery patients with low-molecular-weight heparins.

PubMed

Schindewolf, M; Paulik, M; Kroll, H; Kaufmann, R; Wolter, M; Boehncke, W-H; Lindhoff-Last, E; Recke, A; Ludwig, R J

2018-04-23

Heparins are widely prescribed for prevention and therapy of arterial and venous thromboembolic diseases. Heparin-induced skin lesions are the most frequent adverse effects of subcutaneous heparin treatment in non-surgical patients (7.5-39.8%); no data exist on surgical patients. Commonly, they are due to a delayed-type hypersensitivity reaction (DTH), but may also be a manifestation of life-threatening heparin-induced thrombocytopenia (HIT). Lesions of both entities resemble initially. The risk of HIT is highest among heparin-anticoagulated orthopedic surgery patients. To determine incidence and causes of heparin-induced skin lesions in major orthopedic surgery patients. In a prospective cohort study consecutive patients with subcutaneous low-molecular-weight heparin (LMWH) treatment were examined for cutaneous adverse effects. Further diagnostics (skin biopsy, clinical/laboratory assessment for thrombosis, bleeding, HIT, cross-allergies) were performed. Six of 316 enrolled patients (1.9%; 95% CI 0.4%-3.4%) developed heparin-induced skin lesions. All were caused by a DTH reaction, none was due to HIT or other rare heparin-associated skin diseases. Therapeutic use (dosage) of LMWH was identified as only risk factor (odds ratio: 3.1, 95%CI: 1.4-4.9; p=0.00141). In addition to DTH, 5 thromboembolic, 4 major bleeding complications but no cases of HIT or cross-allergies were observed. Orthopedic surgery patients have - unlike non-surgical patients - a low risk for heparin-induced skin lesions during LMWH treatment; all lesions were due to a DTH reaction. The risk for DTH differs considerably between individual patient cohorts. No association with HIT was observed. These data help to tailor anticoagulatory treatment individually and to increase patient safety. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Transcriptional Analysis of the vanC Cluster from Enterococcus gallinarum Strains with Constitutive and Inducible Vancomycin Resistance

PubMed Central

Panesso, Diana; Abadía-Patiño, Lorena; Vanegas, Natasha; Reynolds, Peter E.; Courvalin, Patrice; Arias, Cesar A.

2005-01-01

The vanC glycopeptide resistance gene cluster encodes enzymes required for synthesis of peptidoglycan precursors ending in d-Ala-d-Ser. Enterococcus gallinarum BM4174 and SC1 are constitutively and inducibly resistant to vancomycin, respectively. Analysis of peptidoglycan precursors in both strains indicated that UDP-MurNAc-tetrapeptide and UDP-MurNAc-pentapeptide[d-Ser] were synthesized in E. gallinarum SC1 only in the presence of vancomycin (4 μg/ml), whereas the “resistance” precursors accumulated in the cytoplasm of BM4174 cells under both inducing and noninducing conditions. Northern hybridization and reverse transcription-PCR experiments revealed that all the genes from the cluster, vanC-1, vanXYC, vanT, vanRC, and vanSC, were transcribed from a single promoter. In the inducible SC1 isolate, transcriptional regulation appeared to be responsible for inducible expression of resistance. Promoter mapping in E. gallinarum BM4174 revealed that the transcriptional start site was located 30 nucleotides upstream from vanC-1 and that the −10 promoter consensus sequence had high identity with that of the vanA cluster. Comparison of the deduced sequence of the vanSC genes from isolates with constitutive and inducible resistance revealed several amino acid substitutions located in the X box (R200L) and in the region between the F and G2 boxes (D312N, D312A, and G320S) of the putative sensor kinase proteins from isolates with constitutive resistance. PMID:15728903

Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

PubMed

Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

2016-03-01

Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dynamic deformation analysis of light-weight mirror

NASA Astrophysics Data System (ADS)

Zhang, Yingtao; Cao, Xuedong; Kuang, Long; Yang, Wei

2012-10-01

In the process of optical dynamic target work, under the effort of the arm of dynamic target, the mirror needs to do circular motion, additional accelerated motion and uniform motion. The maximum acceleration is 10°/s2 and the maximum velocity is 30°/s. In this paper, we mostly analyze the dynamic deformation of a 600 mm honeycomb light-weight mirror of a certain dynamic target. Using the FEA (finite element analysis) method, first of all, we analyze the deformation of the light-weight mirror induced in gravity at different position; later, the dynamic deformation of light-weight mirror is analyzed in detailed. The analysis results indicate that, when the maximum acceleration is 10°/s2 and the maximum velocity is 30°/s, the centripetal force is 5% of the gravity at the equal mass, and the dynamic deformation of the mirror is 6.1% of the deformation induced by gravity.

Improved nutritional status and bone health after diet-induced weight loss in sedentary osteoarthritis patients: a prospective cohort study.

PubMed

Christensen, P; Bartels, E M; Riecke, B F; Bliddal, H; Leeds, A R; Astrup, A; Winther, K; Christensen, R

2012-04-01

Obese subjects are commonly deficient in several micronutrients. Weight loss, although beneficial, may also lead to adverse changes in micronutrient status and body composition. The objective of the study is to assess changes in micronutrient status and body composition in obese individuals after a dietary weight loss program. As part of a dietary weight loss trial, enrolling 192 obese patients (body mass index >30 kg/m2) with knee osteoarthritis (>50 years of age), vitamin D, ferritin, vitamin B12 and body composition were measured at baseline and after 16 weeks. All followed an 8-week formula weight-loss diet 415-810 kcal per day, followed by 8 weeks on a hypo-energetic 1200 kcal per day diet with a combination of normal food and formula products. Statistical analyses were based on paired samples in the completer population. A total of 175 patients (142 women), 91%, completed the 16-week program and had a body weight loss of 14.0 kg (95% confidence interval: 13.3-14.7; P<0.0001), consisting of 1.8 kg (1.3-2.3; P<0.0001) lean body mass (LBM) and 11.0 kg (10.4-11.6; P<0.0001) fat mass. Bone mineral content (BMC) did not change (-13.5 g; P=0.18), whereas bone mineral density (BMD) increased by 0.004 g/cm2 (0.001-0.008 g/cm2; P=0.025). Plasma vitamin D and B(12) increased by 15.3 nmol/l (13.2-17.3; P<0.0001) and 43.7 pmol/l (32.1-55.4; P<0.0001), respectively. There was no change in plasma ferritin. This intensive program with formula diet resulted in increased BMD and improved vitamin D and B12 levels. Ferritin and BMC were unchanged and loss of LBM was only 13% of the total weight loss. This observational evidence supports use of formula diet-induced weight loss therapy in obese osteoarthritis patients.

Low molecular weight fucoidan ameliorates streptozotocin-induced hyper-responsiveness of aortic smooth muscles in type 1 diabetes rats.

PubMed

Liang, Zhengyang; Zheng, Yuanyuan; Wang, Jing; Zhang, Quanbin; Ren, Shuang; Liu, Tiantian; Wang, Zhiqiang; Luo, Dali

2016-09-15

Low molecular weight fucoidan (LMWF) was prepared from Laminaria japonica Areschoug, a popular seafood and medicinal plant consumed in Asia. Chinese have long been using it as a traditional medicine for curing hypertension and edema. This study was intent to investigate the possible beneficial effect of LMWF on hyper-responsiveness of aortic smooth muscles instreptozotocin (STZ)-induced type 1 diabetic rats. Sprague-Dawley rats were made diabetic by injection of STZ, followed by the administration of LMWF (50 or 100mg/kg/day) or probucol (100mg/kg/day) for 12 weeks. Body weight, blood glucose level, basal blood pressure, serum lipid profiles, oxidative stress, prostanoids production, and vasoconstriction response of endothelium-denuded aorta rings to phenylephrine were measured by Real time-PCR, Western blots, ELISA assay, and force myograph, respectively. LMWF (100mg/kg/day)-treated group showed robust improvements on STZ-induced body weight-loss, hypertension, and hyperlipidaemia as indicated by decreased serum level of total cholesterol, triglyceride, and low density lipoprotein cholesterol; while probucol, a lipid-modifying drug with antioxidant properties, displayed mild effects. In addition, LMWF appreciably ameliorated STZ-elicited hyper-responsiveness and oxidative stress in aortic smooth muscles as indicated by decreased superoxide level, increased glutathione content and higher superoxide dismutase activity. Furthermore, administration with LMWF dramatically prevented cyclooxygenase-2 stimulation and restored the up-regulation of thromboxane synthase and down-regulation of 6-keto-PGF1α (a stable metabolic product of prostaglandin I2) in the STZ-administered rats. This study demonstrates for the first time that LMWF can protect against hyperlipidaemia, hypertension, and hyper-responsiveness of aortic smooth muscles in type 1 diabetic rat via, at least in part, amelioration of oxidative stress and restoration of prostanoids levels in aortic smooth muscles

Effect of exercise intensity on weight changes and sexual hormones (androstenedione and free testosterone) in female rats with estradiol valerate-induced PCOS

PubMed Central

2014-01-01

Introduction Weight gain and fat accumulation are predisposing factors of PCOS. Life-style modification, including increasing physical activity, is the first line approach in managing PCOS. The objective of this study is to assess the effect of exercise intensity on weight changes, androstenedione and free testosterone level in female rats with estradiol valerate induced PCOS. Method and materials 40 female Wistar rats were selected (180 ± 20 g). They had every 2 to 3 consecutive estrous cycles during 12 to 14 days. The study was approved by ethical committee of Jahrom University of Medical Sciences. The first two groups were divided into control (n = 10) and polycystic (n = 30) that were induced PCOS by estradiol valerate injection after 60 days. The polycystic groups were divided into three groups of sham (n = 10), experiment group with low-intensity exercise (pco + l.exe) (n = 10) and experiment group with moderate intensity exercise (pco + m.exe) (n = 10). Exercises were performed during 6 sessions of 60 minutes per week for 8 weeks. (Moderate intensity: 28 m/min-70%–75%VO2Max. Low intensity (20 m/min-50%–55%VO2Max) running at 0 slope, 1 h/day, 6 days/week). ANOVA and LSD test were used for data analysis. Results In the present study, no significant differences were found in the decrease of total weights of rats. And also androstenedione level changes in experiment groups were higher compared to control group but no significant differences were found, also free testosterone level was significantly higher than the observer group. Conclusion According to weight changes and sexual hormones (Free testosterone and androstenedione) exercise training especially with low intensity may improve symptoms of polycystic ovary syndrome. PMID:24708600

Body Weight Relationships in Early Marriage: Weight Relevance, Weight Comparisons, and Weight Talk

PubMed Central

Bove, Caron F.; Sobal, Jeffery

2011-01-01

This investigation uncovered processes underlying the dynamics of body weight and body image among individuals involved in nascent heterosexual marital relationships in Upstate New York. In-depth, semi-structured qualitative interviews conducted with 34 informants, 20 women and 14 men, just prior to marriage and again one year later were used to explore continuity and change in cognitive, affective, and behavioral factors relating to body weight and body image at the time of marriage, an important transition in the life course. Three major conceptual themes operated in the process of developing and enacting informants’ body weight relationships with their partner: weight relevance, weight comparisons, and weight talk. Weight relevance encompassed the changing significance of weight during early marriage and included attracting and capturing a mate, relaxing about weight, living healthily, and concentrating on weight. Weight comparisons between partners involved weight relativism, weight competition, weight envy, and weight role models. Weight talk employed pragmatic talk, active and passive reassurance, and complaining and critiquing criticism. Concepts emerging from this investigation may be useful in designing future studies of and approaches to managing body weight in adulthood. PMID:21864601

Induction of a melanoma-specific antibody response by a monovalent, but not a divalent, synthetic GM2 neoglycopeptide.

PubMed

Bay, S; Fort, S; Birikaki, L; Ganneau, C; Samain, E; Coïc, Y-M; Bonhomme, F; Dériaud, E; Leclerc, C; Lo-Man, R

2009-04-01

The GM2 ganglioside represents an important target for specific anticancer immunotherapy. We designed and synthesized a neoglycopeptide immunogen displaying one or two copies of the GM2 tetrasaccharidic moiety. These glycopeptides were prepared using the Huisgen cycloaddition, which enables the efficient ligation of the alkyne-functionalized biosynthesized GM2 with an azido CD4(+) T cell epitope peptide. It is worth noting that the GM2 can be produced on a gram scale in bacteria, which can be advantageous for a scale-up of the process. We show here for the first time that a fully synthetic glycopeptide, which is based on a ganglioside carbohydrate moiety, can induce human tumor cell-specific antibodies after immunization in mice. Interestingly, the monovalent, but not the divalent, form of GM2 peptide construct induced antimelanoma antibodies. Unlike traditional vaccines, this vaccine is a pure chemically-defined entity, a key quality for consistent studies and safe clinical evaluation. Therefore, such carbohydrate-peptide conjugate represents a promising cancer vaccine strategy for active immunotherapy targeting gangliosides.

Long-term persistence of hormonal adaptations to weight loss.

PubMed

Sumithran, Priya; Prendergast, Luke A; Delbridge, Elizabeth; Purcell, Katrina; Shulkes, Arthur; Kriketos, Adamandia; Proietto, Joseph

2011-10-27

After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss. We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite. Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001). One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

The structure of tracheobronchial mucins from cystic fibrosis and control patients.

PubMed

Gupta, R; Jentoft, N

1992-02-15

Tracheobronchial mucin samples from control and cystic fibrosis patients were purified by gel filtration chromatography on Sephacryl S-1000 and by density gradient centrifugation. Normal secretions contained high molecular weight (approximately 10(7] mucins, whereas the cystic fibrosis secretions contained relatively small amounts of high molecular weight mucin together with larger quantities of lower molecular weight mucin fragments. These probably represent products of protease digestion. Reducing the disulfide bonds in either the control or cystic fibrosis high molecular weight mucin fractions released subunits of approximately 2000 kDa. Treating these subunits with trypsin released glycopeptides of 300 kDa. Trypsin treatment of unreduced mucin also released fragments of 2000 kDa that could be converted into 300-kDa glycopeptides upon disulfide bond reduction. Thus, protease-susceptible linkages within these mucins must be cross-linked by disulfide bonds so that the full effects of proteolytic degradation of mucins remain cryptic until disulfide bonds are reduced. Since various combinations of protease treatment and disulfide bond reduction release either 2000- or 300-kDa fragments, these fragments must represent important elements of mucin structure. The high molecular weight fractions of cystic fibrosis mucins appear to be indistinguishable from control mucins. Their amino acid compositions are the same, and various combinations of disulfide bond reduction and protease treatment release products of identical size and amino acid composition. Sulfate and carbohydrate compositions did vary considerably from sample to sample, but the limited number of samples tested did not demonstrate a cystic fibrosis-specific pattern. Thus, tracheobronchial mucins from cystic fibrosis and control patients are very similar, and both share the same generalized structure previously determined for salivary, cervical, and intestinal mucins.

Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Blood Glucose, Body Weight and Feed Intake of Streptozotocin-induced Diabetic Rats.

PubMed

M, Iroaganachi; C O, Eleazu; P N, Okafor; N, Nwaohu

2014-01-01

To determine the effect of unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) on blood glucose (BG), feed intake (FI) and weight of streptozotocin (STZ) induced diabetic rats. Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) and Group 2 (diabetic) received standard rat feed; Group 3 received unripe plantain incorporated feed (810 /kg body weight) and Group 4 received unripe plantain+ginger incorporated feed (710:100 g/kg body weight). The weights and FI of the rats were measured daily throughout the experimentation. Groups 3 and 4 rats had 159.52% and 71.83% decreases in BG but 24.91% and 35.32% decreases in weights compared with groups 1 and 2 rats that had 2.09% and 22.94% increases in BG with 13.42% increase and 45.36% decrease in weights respectively. The FI of the experimental rats did not differ significantly from each other (P>0.05) at the end of experimentation. The standard rat feed contained higher amounts of Ca but lower amounts of Mg and Fe compared with the unripe plantain and unripe plantain+ginger incorporated feeds. Combination of unripe plantain and ginger at the dose used in the management of diabetes was not very effective compared with unripe plantain alone.

Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Blood Glucose, Body Weight and Feed Intake of Streptozotocin-induced Diabetic Rats

PubMed Central

M, Iroaganachi; C.O, Eleazu; P.N, Okafor; N, Nwaohu

2015-01-01

Objective: To determine the effect of unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) on blood glucose (BG), feed intake (FI) and weight of streptozotocin (STZ) induced diabetic rats. Methods: Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) and Group 2 (diabetic) received standard rat feed; Group 3 received unripe plantain incorporated feed (810 /kg body weight) and Group 4 received unripe plantain+ginger incorporated feed (710:100 g/kg body weight). The weights and FI of the rats were measured daily throughout the experimentation. Results: Groups 3 and 4 rats had 159.52% and 71.83% decreases in BG but 24.91% and 35.32% decreases in weights compared with groups 1 and 2 rats that had 2.09% and 22.94% increases in BG with 13.42% increase and 45.36% decrease in weights respectively. The FI of the experimental rats did not differ significantly from each other (P>0.05) at the end of experimentation. The standard rat feed contained higher amounts of Ca but lower amounts of Mg and Fe compared with the unripe plantain and unripe plantain+ginger incorporated feeds. Conclusion: Combination of unripe plantain and ginger at the dose used in the management of diabetes was not very effective compared with unripe plantain alone. PMID:25674161

Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status.

PubMed

Harris, Ruth B S; Mitchell, Tiffany D; Simpson, Jacob; Redmann, Stephen M; Youngblood, Bradley D; Ryan, Donna H

2002-01-01

Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.

Polymer/Carbon Nanotube Networks for Smart, Self-Repairing and Light-Weighted Nanocomposites

DTIC Science & Technology

2012-11-05

was develop smart, strong, and light-weight polymer/carbon nanotube (CNT) composites which will sense tribologically induced damages and self-heal by...light-weight polymer/carbon nanotube (CNT) composites which will sense tribologically induced damages and self-heal by inhibiting such degradation...one of support references for EPSRC instrument grant application for Micro Materials NanoTest Vantage Testing Suite with NTX4Controller. The grant

Glyoxal administration induces formation of high molecular weight aggregates of hemoglobin exhibiting amyloidal nature in experimental rats: An in vivo study.

PubMed

Banerjee, Sauradipta; Chakraborti, Abhay Sankar

2016-12-01

Glyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs). In the present study, we have investigated the effect of glyoxal on experimental rat hemoglobin in vivo after external administration of the α-dicarbonyl compound in animals. Gel electrophoretic profile of hemolysate collected from glyoxal-treated rats (32mg/kg body wt. dose) after one week exhibited the presence of some high molecular weight protein bands that were found to be absent for control, untreated rats. Mass spectrometric and absorption studies indicated that the bands represented hemoglobin. Further studies revealed that the fraction exhibited the presence of intermolecular cross β-sheet structure. Thus glyoxal administration induces formation of high molecular weight aggregates of hemoglobin with amyloid characteristics in rats. Aggregated hemoglobin fraction was found to exhibit higher stability compared to glyoxal-untreated hemoglobin. As evident from mass spectrometric studies, glyoxal was found to modify Arg-30β and Arg-31α of rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to induce amyloid-like aggregation of hemoglobin in rats. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, the above findings may be physiologically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci.

PubMed

Hughes, C S; Longo, E; Phillips-Jones, M K; Hussain, R

2017-08-01

A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanR A S A two-component system, comprising the histidine sensor kinase VanS A and the partner response regulator VanR A . The nature of the activating ligand for VanS A has not been identified, therefore this work sought to identify and characterise ligand(s) for VanS A . In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanS A protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanS A with different affinities (vancomycin 70μM; teicoplanin 30 and 170μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanS A , proposing them as activators of type A vancomycin resistance in the enterococci. Copyright © 2017 Diamond Light Source Ltd. Published by Elsevier B.V. All rights reserved.

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals.

PubMed

Coker, Robert H; Miller, Sharon; Schutzler, Scott; Deutz, Nicolaas; Wolfe, Robert R

2012-12-11

Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR) would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR). We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day): 1) EAAMR or a 2) competitive meal replacement (CMR) in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial.

PubMed

Tek, Cenk; Guloksuz, Sinan; Srihari, Vinod H; Reutenauer, Erin L

2013-06-27

Obesity is a growing health problem leading to high rates of mortality and morbidity in patients with severe mental illness (SMI). The increased rate of obesity is largely attributed to antipsychotic use. The effect of antipsychotic medications on H1 and 5HT2 receptors has been associated with weight gain, but there is also a substantial amount of evidence showing that D2 receptor blockade may be responsible for weight gain by interacting with the dopamine-opioid system. Unfortunately, current available medications for weight loss have limited efficacy in this population. Naltrexone, an opioid receptor antagonist, may be a promising agent to reduce antipsychotic induced weight gain by decreasing food cravings. We aim to investigate the safety and efficacy of two doses of naltrexone (25 mg & 50 mg) versus placebo for weight and health risk reduction in overweight and obese individuals (BMI ≥ 28) with SMI, who gained weight while being treated with antipsychotics. One hundred and forty four patients will be recruited throughout the greater New Haven area. The participants will be randomized to naltrexone 25 mg/day, naltrexone 50 mg/day, or placebo in a 1:1:1 ratio. Participants will be on the study medication for 52 weeks, and assessed weekly for the first 4 weeks and bi-weekly thereafter. The primary outcome measurements are weight reduction and percentage achieving clinically significant weight loss (5% of total body weight). Waist circumference, body mass index, serum lipid profile, fasting glucose, and glycosylated hemoglobin are the secondary outcome measures. The effect of naltrexone on other outcome measurements such as schizophrenia symptoms, depression, dietary consumption, quality of life, cognitive functioning, physical activity, metabolism/inflammation markers, serum leptin, ghrelin, peptide YY, adinopectin, high sensitivity CRP, interleukin 6, interleukin-1B, interleukin-18, and tumor necrosis factor alpha (TNF-α) will be evaluated. The data will be

Intracellular leptin signaling following effective weight loss.

PubMed

Sahin-Efe, Ayse; Polyzos, Stergios A; Dincer, Fadime; Zaichenko, Lesya; McGovern, Rosemary; Schneider, Benjamin; Mantzoros, Christos S

2015-08-01

To investigate the effect of ex-vivo leptin treatment before and after weight loss on key-molecules of intracellular leptin signaling in peripheral blood mononuclear cells (PBMCs) of obese women. Five healthy obese women underwent a 12-week medical nutrition treatment aiming at inducing 10% weight loss. Isolated PBMCs at baseline, and at weeks 8 and 12 were treated with increasing leptin doses (0, 25 and 75 ng/ml) for 30 min. The phosphorylation of signal transducer and activator of transcription (STAT)3, extracellular-signal-regulated kinase (ERK), protein kinase B (Akt) and 5' adenosine monophosphate-activated protein kinase (AMPK) of PBMCs was analyzed using Western blotting. Women lost 10 ± 1% and 13 ± 1% of weight at week 8 and 12, respectively. Circulating leptin and insulin significantly decreased from 39.5 ± 7.7 to 12.2 ± 2.4 ng/ml (p = 0.026) and from 13.0 ± 1.6 to 5.4 ± 0.9 μU/ml (p = 0.005) at week 12, respectively. In the ex vivo study, a significant decrease in STAT3 phosphorylation was observed in the control group after weight loss. Treatment of PBMCs with leptin 75 ng/ml increased significantly ERK, STAT3 and Akt phosphorylation, but no weight loss induced change was observed in response to leptin treatment ex vivo. A 10%-15% weight loss decreases baseline STAT3 phosphorylation ex vivo, but does not alter the effect of increasing doses of leptin on the incremental intracellular phosphorylation of STAT3, ERK, Akt and AMPK. Supraphysiologic leptin doses (75 ng/ml) result in higher protein phosphorylation compared to either physiologic doses or no treatment, before and after weight loss. Copyright © 2015 Elsevier Inc. All rights reserved.

Green tea extract induces genes related to browning of white adipose tissue and limits weight-gain in high energy diet-fed rat.

PubMed

Chen, Li-Han; Chien, Yi-Wen; Liang, Chung-Tiang; Chan, Ching-Hung; Fan, Meng-Han; Huang, Hui-Yu

2017-01-01

Background: A wealth of research has reported on the anti-obesity effects of green tea extract (GTE). Although browning of white adipose tissue (WAT) has been reported to attenuate obesity, no study has disclosed the effects of GTE on browning in Sprague Dawley rats. Objectives: The aims of the study were to investigate the effects of GTE on anti-obesity and browning, and their underlying mechanisms. Methods: Four groups of rats (n=10/group) were used including a normal diet with vehicle treatment, and a high-energy diet (HED) with vehicle or GTE by oral gavage at 77.5 or 155 mg/kg/day for 8 weeks. Body weight, fat accumulation, and serum biochemical parameters were used to evaluate obesity. The gene expressions were analyzed using RT-qPCR and western blotting. Results: GTE modulated HED-induced body weight, fat accumulation, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein, free fatty acids, aspartate aminotransferase, and alanine aminotransferase. Moreover, GTE enhanced the serum high-density lipoprotein. Most importantly, the biomarkers of beige adipose tissue were up-regulated in WAT in GTE-given groups. GTE induced genes involved in different pathways of browning, and reduced transducin-like enhancer protein-3 in WAT. Conclusion: Our results suggest that GTE may improve obesity through inducing browning in HED-fed rats. Abbreviations : ALT: Alanine transaminase; AST: Aspartate transaminase; BAT: Brown adipose tissue; BMP-7: Bone morphogenetic protein-7; BW: Body weight; CIDEA: Cell death activator; CPT-1: Carnitine palmitoyltransferase-1; EFP: Epididymal fat pad; FFA: Free fatty acid; FGF-21: Fibroblast growth factor-21; GTE: Green tea extract; HDL: High-density lipoprotein; HED: high-energy diet; LDL: Low-density lipoprotein; MFP: Mesenteric fat pad; PGC-1α: Activates PPAR-γ coactivator-1; PPAR-γ: Peroxisome proliferator-activated receptor-γ; PRDM-16: PR domain containing 16; RFP: Renal fat pad; SD: Sprague Dawley; TC: Total

Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents.

PubMed

Albaugh, Vance L; Henry, Cathy R; Bello, Nicholas T; Hajnal, Andras; Lynch, Susan L; Halle, Beth; Lynch, Christopher J

2006-01-01

To characterize a model of atypical antipsychotic drug-induced obesity and evaluate its mechanism. Chronically, olanzapine or clozapine was self-administered via cookie dough to rodents (Sprague-Dawley or Wistar rats; C57Bl/6J or A/J mice). Chronic studies measured food intake, body weight, adiponectin, active ghrelin, leptin, insulin, tissue wet weights, glucose, clinical chemistry endpoints, and brain dopaminergic D2 receptor density. Acute studies examined food intake, ghrelin, leptin, and glucose tolerance. Olanzapine (1 to 8 mg/kg), but not clozapine, increased body weight in female rats only. Weight changes were detectable within 2 to 3 days and were associated with hyperphagia starting approximately 24 hours after the first dose. Chronic administration (12 to 29 days) led to adiposity, hyperleptinemia, and mild insulin resistance; no lipid abnormalities or changes in D2 receptor density were observed. Topiramate, which has reversed weight gain from atypical antipsychotics in humans, attenuated weight gain in rats. Acutely, olanzapine, but not clozapine, lowered plasma glucose and leptin. Increases in glucose, insulin, and leptin following a glucose challenge were also blunted. A model of olanzapine-induced obesity was characterized which shares characteristics of patients with atypical antipsychotic drug-induced obesity; these characteristics include hyperphagia, hyperleptinemia, insulin resistance, and weight gain attenuation by topiramate. This model may be a useful and inexpensive model of uncomplicated obesity amenable to rapid screening of weight loss drugs. Olanzapine-induced weight gain may be secondary to hyperphagia associated with acute lowering of plasma glucose and leptin, as well as the inability to increase plasma glucose and leptin following a glucose challenge.

Hormonal and Metabolic Effects of Olanzapine and Clozapine Related to Body Weight in Rodents

PubMed Central

Albaugh, Vance L.; Henry, Cathy R.; Bello, Nicholas T.; Hajnal, Andras; Lynch, Susan L.; Halle, Beth; Lynch, Christopher J.

2009-01-01

Objective To characterize a model of atypical antipsychotic drug-induced obesity and evaluate its mechanism. Research Methods and Procedures Chronically, olanzapine or clozapine was self-administered via cookie dough to rodents (Sprague-Dawley or Wistar rats; C57Bl/6J or A/J mice). Chronic studies measured food intake, body weight, adiponectin, active ghrelin, leptin, insulin, tissue wet weights, glucose, clinical chemistry endpoints, and brain dopaminergic D2 receptor density. Acute studies examined food intake, ghrelin, leptin, and glucose tolerance. Results Olanzapine (1 to 8 mg/kg), but not clozapine, increased body weight in female rats only. Weight changes were detectable within 2 to 3 days and were associated with hyperphagia starting ~24 hours after the first dose. Chronic administration (12 to 29 days) led to adiposity, hyperleptinemia, and mild insulin resistance; no lipid abnormalities or changes in D2 receptor density were observed. Topiramate, which has reversed weight gain from atypical anti-psychotics in humans, attenuated weight gain in rats. Acutely, olanzapine, but not clozapine, lowered plasma glucose and leptin. Increases in glucose, insulin, and leptin following a glucose challenge were also blunted. Discussion A model of olanzapine-induced obesity was characterized which shares characteristics of patients with atypical antipsychotic drug-induced obesity; these characteristics include hyperphagia, hyperleptinemia, insulin resistance, and weight gain attenuation by topiramate. This model may be a useful and inexpensive model of uncomplicated obesity amenable to rapid screening of weight loss drugs. Olanzapine-induced weight gain may be secondary to hyperphagia associated with acute lowering of plasma glucose and leptin, as well as the inability to increase plasma glucose and leptin following a glucose challenge. PMID:16493121

Improved nutritional status and bone health after diet-induced weight loss in sedentary osteoarthritis patients: a prospective cohort study

PubMed Central

Christensen, P; Bartels, E M; Riecke, B F; Bliddal, H; Leeds, A R; Astrup, A; Winther, K; Christensen, R

2012-01-01

BACKGROUND/OBJECTIVES: Obese subjects are commonly deficient in several micronutrients. Weight loss, although beneficial, may also lead to adverse changes in micronutrient status and body composition. The objective of the study is to assess changes in micronutrient status and body composition in obese individuals after a dietary weight loss program. SUBJECTS/METHODS: As part of a dietary weight loss trial, enrolling 192 obese patients (body mass index >30 kg/m2) with knee osteoarthritis (>50 years of age), vitamin D, ferritin, vitamin B12 and body composition were measured at baseline and after 16 weeks. All followed an 8-week formula weight-loss diet 415–810 kcal per day, followed by 8 weeks on a hypo-energetic 1200 kcal per day diet with a combination of normal food and formula products. Statistical analyses were based on paired samples in the completer population. RESULTS: A total of 175 patients (142 women), 91%, completed the 16-week program and had a body weight loss of 14.0 kg (95% confidence interval: 13.3–14.7; P<0.0001), consisting of 1.8 kg (1.3–2.3; P<0.0001) lean body mass (LBM) and 11.0 kg (10.4–11.6; P<0.0001) fat mass. Bone mineral content (BMC) did not change (-13.5 g; P=0.18), whereas bone mineral density (BMD) increased by 0.004 g/cm2 (0.001–0.008 g/cm2; P=0.025). Plasma vitamin D and B12 increased by 15.3 nmol/l (13.2–17.3; P<0.0001) and 43.7 pmol/l (32.1–55.4; P<0.0001), respectively. There was no change in plasma ferritin. CONCLUSIONS: This intensive program with formula diet resulted in increased BMD and improved vitamin D and B12 levels. Ferritin and BMC were unchanged and loss of LBM was only 13% of the total weight loss. This observational evidence supports use of formula diet-induced weight loss therapy in obese osteoarthritis patients. PMID:22190136

An enrichment method based on synergistic and reversible covalent interactions for large-scale analysis of glycoproteins.

PubMed

Xiao, Haopeng; Chen, Weixuan; Smeekens, Johanna M; Wu, Ronghu

2018-04-27

Protein glycosylation is ubiquitous in biological systems and essential for cell survival. However, the heterogeneity of glycans and the low abundance of many glycoproteins complicate their global analysis. Chemical methods based on reversible covalent interactions between boronic acid and glycans have great potential to enrich glycopeptides, but the binding affinity is typically not strong enough to capture low-abundance species. Here, we develop a strategy using dendrimer-conjugated benzoboroxole to enhance the glycopeptide enrichment. We test the performance of several boronic acid derivatives, showing that benzoboroxole markedly increases glycopeptide coverage from human cell lysates. The enrichment is further improved by conjugating benzoboroxole to a dendrimer, which enables synergistic benzoboroxole-glycan interactions. This robust and simple method is highly effective for sensitive glycoproteomics analysis, especially capturing low-abundance glycopeptides. Importantly, the enriched glycopeptides remain intact, making the current method compatible with mass-spectrometry-based approaches to identify glycosylation sites and glycan structures.

No effect of weight cycling on the post-career BMI of weight class elite athletes

PubMed Central

2013-01-01

Background Repetitions of pre-competition weight-loss diets done by athletes participating in weight class sports can be regarded as periods of weight cycling. The aim of the present study is to identify the long term post-career (22 years) evolutionary profile of athletes’ BMI after such weight cycling. Methods One hundred and thirty-six retired French athletes who participated in major international competitions in weight class sports (rowers, wrestlers, boxers, and judokas) were included. Former and current body mass, height, dietary characteristics during the career (annual frequency, amount of weight lost), current physical activity, and answers on the eating-attitude test were collected by phone interview (consistency was tested by comparison with measured weight). We performed ANOVA tests for comparison between groups (sport, dieting), post-hoc tests (Bonferroni test) to identify differences within groups. BMI’s changes were treated using a mixed model. Results The recorded weight changes did not depend upon time since retirement. Between 18 y and 50 y, athletes’ BMI increased by 3.2 kg/m2 compared to the 4.2 kg/m2 increase in the general population. This increase was independent of the number of diets during the career. Retired athletes declared a mean weekly physical activity of 4.8 h ± 4.3. The eating-attitude test showed low scores for all sports without any correlation to diet characteristics. Conclusion Weight cycling during an athletic career does not induce a massive weight gain after retirement, probably due to the high level of physical activity still practiced after retirement by these athletes. PMID:23711106

Catechin supplemented in a FOS diet induces weight loss by altering cecal microbiota and gene expression of colonic epithelial cells.

PubMed

Luo, Jianming; Han, Lulu; Liu, Liu; Gao, Lijuan; Xue, Bin; Wang, Yong; Ou, Shiyi; Miller, Michael; Peng, Xichun

2018-05-23

Our previous study showed that catechin controlled rats' body weights and changed gut microbiota composition when supplemented into a high-fructo-oligosaccharide (FOS) diet. This experiment is devised to further confirm the relationship between specific bacteria in the colon and body weight gain, and to investigate how specific bacteria impact body weight by changing the expression of colonic epithelial cells. Forty obese rats were divided into four groups: three catechin-supplemented groups with a high-FOS diet (100, 400, and 700 mg kg-1 d-1 catechin, orally administered) and one group with a high-FOS diet only. Food consumption and body weights were recorded each week. After one month of treatment, rats' cecal content and colonic epithelial cells were individually collected and analyzed with MiSeq and gene expression profiling techniques, respectively. Results identified some specific bacteria at the genus level-including the increased Parabacteroides sp., Prevotella sp., Robinsoniella sp., [Ruminococcus], Phascolarctobacterium sp. and an unknown genus of YS2, and the decreased Lachnospira sp., Oscillospira sp., Ruminococcus sp., an unknown genus of Peptococcaceae and an unknown genus of Clostridiales in rats' cecum-and eight genes-including one downregulated Pla2g2a and seven upregulated genes: Apoa1, Apoa4, Aabr07073400.1, Fabp4, Pik3r5, Dgat2 and Ptgs2 of colonic epithelial cells-that were due to the consumption of catechin. Consequently, various biological functions in connection with energy metabolism in colonic epithelial cells were altered, including fat digestion and absorption and the regulation of lipolysis in adipocytes. In conclusion, catechin induces host weight loss by altering gut microbiota and gene expression and function in colonic epithelial cells.

Purse-string transoral outlet reduction (TORe) is effective at inducing weight loss and improvement in metabolic comorbidities after Roux-en-Y gastric bypass.

PubMed

Jirapinyo, Pichamol; Kröner, Paul T; Thompson, Christopher C

2018-04-01

BACKGROUND AND STUDY AIMS : Transoral outlet reduction (TORe), performed using a traditional interrupted or a recently described purse-string suture pattern, is effective at inducing short- and mid-term weight loss in patients with weight regain after Roux-en-Y gastric bypass (RYGB). We aimed to determine the technical feasibility and safety of purse-string TORe and to assess its impact on weight and metabolic profiles.  RYGB patients undergoing purse-string TORe were included. The gastrojejunal anastomosis (GJA) was ablated using argon plasma coagulation or dissected using endoscopic submucosal dissection. A suture was used to place stitches around the GJA in a continuous ring fashion. The suture was cinched over a balloon (8 - 12 mm). The primary outcome was technical feasibility. Secondary outcomes were the percentage of total body weight lost (%TWL), adverse events, impact on comorbidities, and predictors of weight loss.  252 RYGB patients underwent 260 purse-string TORes. They had regained 52.6 ± 46.4 % of lost weight and weighed 107.6 ± 24.6 kg. The technical success rate was 100 %. At 6 and 12 months, %TWL was 9.6 ± 6.3 and 8.4 ± 8.2. Two serious adverse events (0.8 %) occurred: gastrointestinal bleeding and GJA stenosis. At 12 months, blood pressure, hemoglobin A 1c , and ALT had improved. Prior weight regain was associated with %TWL at 12 months ( β  = 0.07, P  = 0.007) after controlling for BMI, pouch size, and number of purse-string rings.  Purse-string TORe to treat weight regain after RYGB is technically feasible and safe. Additionally, it is associated with improvement in weight and comorbidity profiles up to 12 months post-procedure. © Georg Thieme Verlag KG Stuttgart · New York.

Antiobesity effects of the beta-cell hormone amylin in diet-induced obese rats: effects on food intake, body weight, composition, energy expenditure, and gene expression.

PubMed

Roth, Jonathan D; Hughes, Heather; Kendall, Eric; Baron, Alain D; Anderson, Christen M

2006-12-01

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 microg/kg.d, 22d) reduced food intake and slowed weight gain: approximately 10% (P<0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P<0.05). Whereas PF decreased lean tissue (P<0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean+/-se, 0.82+/-0.0, 0.81+/-0.0, respectively; P<0.05) similar to VEH (0.84+/-0.01). Energy expenditure (EE mean+/-se) tended to be reduced by PF (5.67+/-0.1 kcal/h.kg) and maintained by amylin (5.86+/-0.1 kcal/h.kg) relative to VEH (5.77+/-0.0 kcal/h.kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74+/-0.09 kcal/.kg; P<0.05) relative to VEH (5.49+/-0.06) and PF (5.38+/-0.07 kcal/h.kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P<0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P<0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.

Corneal protection with high-molecular-weight hyaluronan against in vitro and in vivo sodium lauryl sulfate-induced toxic effects.

PubMed

Pauloin, Thierry; Dutot, Mélody; Liang, Hong; Chavinier, Emilie; Warnet, Jean-Michel; Rat, Patrice

2009-10-01

The aim of this study was to investigate high-molecular-weight hyaluronan (HA-HMW) corneal protection against sodium lauryl sulfate (SLS)-induced toxic effects with in vitro and in vivo experimental approaches. In vitro experiments consisted of a human corneal epithelial cell line incubated with HA-HMW, rinsed, and incubated with SLS. Cell viability, oxidative stress, chromatin condensation, caspase-3, -8, -9, and P2X7 cell death receptor activation, interleukin-6, and interleukin-8 production were investigated. In vivo experiments consisted of 36 New Zealand white rabbits treated for 3 days, 3 times per day, with HA-HMW or phosphate-buffered salt solution. At day 4, eyes were treated with SLS. Clinical observation and in vivo confocal microscopy using the Rostock Cornea Module of the Heidelberg Retina Tomograph-II were performed to evaluate and to compare SLS-induced toxicity between eyes treated with HA-HMW and eyes treated with phosphate-buffered salt solution. In vitro data indicate that exposure of human corneal epithelial cells to HA-HMW significantly decreased SLS-induced oxidative stress, apoptosis, and inflammation cytokine production. In vivo data indicate that SLS cornea injuries, characterized by damaged corneal epithelium, damaged anterior stroma, and inflammatory infiltrations, were attenuated with HA-HMW treatment. A good correlation was seen between in vitro and in vivo findings showing that HA-HMW decreases SLS-induced toxic effects and protects cornea.

Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats.

PubMed

Adam, Clare L; Gratz, Silvia W; Peinado, Diana I; Thomson, Lynn M; Garden, Karen E; Williams, Patricia A; Richardson, Anthony J; Ross, Alexander W

2016-01-01

Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity.

RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice.

PubMed

Yang, R; Castriota, G; Chen, Y; Cleary, M A; Ellsworth, K; Shin, M K; Tran, J-Lv; Vogt, T F; Wu, M; Xu, S; Yang, X; Zhang, B B; Berger, J P; Qureshi, S A

2011-02-01

To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.

Single Fluid-Filled Intragastric Balloon Safe and Effective for Inducing Weight Loss in a Real-World Population.

PubMed

Vargas, Eric J; Pesta, Carl M; Bali, Ahmad; Ibegbu, Eric; Bazerbachi, Fateh; Moore, Rachel L; Kumbhari, Vivek; Sharaiha, Reem Z; Curry, Trace W; DosSantos, Gina; Schmitz, Ramsey; Agnihotri, Abhishek; Novikov, Aleksey A; Pitt, Tracy; Dunlap, Margo K; Herr, Andrea; Aronne, Louis; Ledonne, Erin; Kadouh, Hoda C; Cheskin, Lawrence J; Mundi, Manpreet S; Acosta, Andres; Gostout, Christopher J; Abu Dayyeh, Barham K

2018-07-01

at the time of balloon placement was associated with increased odds of removal before 6 months (odds ratio, 3.92; 95% CI, 1.24-12.41). Total body weight lost at 3 months was 8.5% ± 4.9% (n = 204), at 6 months was 11.8% ± 7.5% (n = 199), and at 9 months was 13.3% ± 10% (n = 47). At 6 months, total body weight losses of 5%, 10%, and 15% were achieved by 88%, 62%, and 31% of patients, respectively. Number of follow-up visits and weight loss at 3 months were associated with increased weight loss at 6 months (β = 0.5 and 1.2, respectively) (P < .05). Mean levels of cholesterol, triglycerides, low-density lipoprotein, and hemoglobin A1c, as well as systolic and diastolic blood pressure, were significantly improved at 6 months after OIB placement (P < .05). In an analysis of a database of patients who received endoscopic placement of the OIB, we found it to be safe, effective at inducing weight loss, and to reduce obesity-related comorbidities in a real-world clinical population. Rates of early removal (before 8 weeks) did not differ significantly between clinical trials and the real-world population, but were affected by use of medications. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Hyperandrogenemia Induced by Letrozole Treatment of Pubertal Female Mice Results in Hyperinsulinemia Prior to Weight Gain and Insulin Resistance.

PubMed

Skarra, Danalea V; Hernández-Carretero, Angelina; Rivera, Alissa J; Anvar, Arya R; Thackray, Varykina G

2017-09-01

Women with polycystic ovary syndrome (PCOS) diagnosed with hyperandrogenism and ovulatory dysfunction have an increased risk of developing metabolic disorders, including type 2 diabetes and cardiovascular disease. We previously developed a model that uses letrozole to elevate endogenous testosterone levels in female mice. This model has hallmarks of PCOS, including hyperandrogenism, anovulation, and polycystic ovaries, as well as increased abdominal adiposity and glucose intolerance. In the current study, we further characterized the metabolic dysfunction that occurs after letrozole treatment to determine whether this model represents a PCOS-like metabolic phenotype. We focused on whether letrozole treatment results in altered pancreatic or liver function as well as insulin resistance. We also investigated whether hyperinsulinemia occurs secondary to weight gain and insulin resistance in this model or if it can occur independently. Our study demonstrated that letrozole-treated mice developed hyperinsulinemia after 1 week of treatment and without evidence of insulin resistance. After 2 weeks of letrozole treatment, mice became significantly heavier than placebo mice, demonstrating that weight gain was not required to develop hyperinsulinemia. After 5 weeks of letrozole treatment, mice exhibited blunted glucose-stimulated insulin secretion, insulin resistance, and impaired insulin-induced phosphorylation of AKT in skeletal muscle. Moreover, letrozole-treated mice exhibited dyslipidemia after 5 weeks of treatment but no evidence of hepatic disease. Our study demonstrated that the letrozole-induced PCOS mouse model exhibits multiple features of the metabolic dysregulation observed in obese, hyperandrogenic women with PCOS. This model will be useful for mechanistic studies investigating how hyperandrogenemia affects metabolism in females. Copyright © 2017 Endocrine Society.

Weight Loss and Diet in Wrestling.

ERIC Educational Resources Information Center

Lopez, Richard

1980-01-01

Most weight loss among wrestlers is accomplished by a combination of fasting, induced sweating, and reduced fluid intake resulting in dehydration in the final days prior to competition. The effects of acute thermal dehydration on cardiovascular dynamics are related to a reduction in plasma volume. (JN)

The temporal impact of chronic intermittent psychosocial stress on high-fat diet-induced alterations in body weight.

PubMed

Finger, Beate C; Dinan, Timothy G; Cryan, John F

2012-06-01

Chronic stress and diet can independently or in concert influence the body's homeostasis over time. Thus, it is crucial to investigate the interplay of these parameters to gain insight into the evolution of stress-induced metabolic and eating disorders. C57BL/6J mice were subjected to chronic psychosocial (mixed model of social defeat and overcrowding) stress in combination with either a high- or low-fat diet for three or six weeks. To determine the evolution of stress and dietary effects, changes in body weight, caloric intake and caloric efficiency were determined as well as circulating leptin, insulin, glucose and corticosterone levels and social avoidance behaviour. Exposure to stress for three weeks caused an increase in weight gain, in caloric intake and in caloric efficiency only in mice on a low-fat diet. However, after six weeks, only stressed mice on a high-fat diet displayed a pronounced inhibition of body weight gain, accompanied by reduced caloric intake and caloric efficiency. Stress decreased circulating leptin levels in mice on a low-fat diet after three weeks and in mice on a high-fat diet after three and six weeks of exposure. Plasma levels of insulin and markers of insulin resistance were blunted in mice on high-fat diet following six weeks of stress exposure. Social avoidance following chronic stress was present in all mice after three and six weeks. This study describes the evolution of the chronic effects of social defeat/overcrowding stress in combination with exposure to high- or low-fat diet. Most importantly, we demonstrate that a six week chronic exposure to social defeat stress prevents the metabolic effects of high-fat diet, by inhibiting an increase in weight gain, caloric intake and efficiency and insulin resistance as well as in plasma leptin and insulin levels. This study highlights the importance of considering the chronic aspects of both parameters and their time-dependent interplay. Copyright © 2011 Elsevier Ltd. All rights

Liraglutide 3.0 mg for weight management: weight-loss dependent and independent effects.

PubMed

Bays, Harold; Pi-Sunyer, Xavier; Hemmingsson, Joanna Uddén; Claudius, Birgitte; Jensen, Christine B; Van Gaal, Luc

2017-02-01

As an adjunct to a reduced-calorie diet and increased physical activity, treatment with liraglutide 3.0 mg for weight management provides a statistically significant and clinically meaningful weight loss of 5.7%-8.0% compared to 1.6%-2.6% with placebo. The objective of this post hoc analysis was to quantify the relative contribution of weight loss to the treatment effects of liraglutide 3.0 mg on key efficacy endpoints. The analysis utilized data from 4725 participants across three randomized, placebo-controlled, double-blind trials that evaluated the efficacy and safety of liraglutide 3.0 mg versus placebo, as an adjunct to a reduced-calorie diet and increased physical activity (ClinicalTrials.gov identifiers: NCT01272219, NCT01272232 and NCT01557166). The duration of two of the trials was 56 weeks; one trial was of 32 weeks' duration. A mediation analysis was performed, which ranked the relative contribution of weight loss to the treatment effects of liraglutide 3.0 mg on key cardiometabolic efficacy endpoints, Apnea-Hypopnea Index (AHI) and health-related quality of life (QoL). A limitation of this type of analysis is that it cannot conclusively prove a causal relationship. In individuals without type 2 diabetes mellitus (T2DM), endpoints predominantly driven by liraglutide-induced weight loss included waist circumference, diastolic blood pressure, triglycerides, high density lipoprotein cholesterol, AHI, and Impact of Weight on Quality of Life-Lite total and physical function scores. Endpoints predominantly independent of weight loss included the glycemic endpoints hemoglobin A1c and fasting plasma glucose in individuals with and without T2DM. Regardless of the degree of dependence on weight loss according to the mediation analysis, greater weight loss was associated with greater improvement in all endpoints. Treatment with liraglutide 3.0 mg contributes to improved cardiometabolic parameters, AHI and health-related QoL through both weight

Modified High-Sucrose Diet-Induced Abdominally Obese and Normal-Weight Rats Developed High Plasma Free Fatty Acid and Insulin Resistance

PubMed Central

Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

2012-01-01

Introduction. Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Methods and Results. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. Conclusion. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle. PMID:23320128

Modified high-sucrose diet-induced abdominally obese and normal-weight rats developed high plasma free fatty acid and insulin resistance.

PubMed

Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

2012-01-01

Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.

Ameliorative Potentials of Cocoyam (Colocasia esculenta L.) and Unripe Plantain (Musa paradisiaca L.) on the Relative Tissue Weights of Streptozotocin-Induced Diabetic Rats

PubMed Central

Eleazu, C. O.; Iroaganachi, M.; Eleazu, K. C.

2013-01-01

Aim. To investigate the ameliorating potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) incorporated feeds on the renal and liver growths of diabetic rats, induced with 55 and 65 mg/kg body weight of Streptozotocin. Method. The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity (SPGR) in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The chemical composition and antioxidant screening of the test feeds were carried out using standard techniques. Results. Administration of the test feeds for 21 days to the diabetic rats of groups 4 and 5, resulted in 58.75% and 38.13% decreases in hyperglycemia and amelioration of their elevated urinary protein, glucose, SPGR, and relative kidney weights. The diabetic rats administered cocoyam incorporated feeds, had 2.71% and 19.52% increases in weight and growth rates, the diabetic rats administered unripe plantain incorporated feeds had 5.12% and 29.52% decreases in weight and growth rates while the diabetic control rats had 28.69%, 29.46%, 248.9% and 250.14% decreases in weights and growth rates. The cocoyam incorporated feeds contained higher antioxidants, minerals and phytochemicals except alkaloids than unripe plantain feed. Conclusion. Cocoyam and unripe plantain could be useful in the management of diabetic nephropathy. PMID:23971053

Ameliorative potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) on the relative tissue weights of streptozotocin-induced diabetic rats.

PubMed

Eleazu, C O; Iroaganachi, M; Eleazu, K C

2013-01-01

To investigate the ameliorating potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) incorporated feeds on the renal and liver growths of diabetic rats, induced with 55 and 65 mg/kg body weight of Streptozotocin. The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity (SPGR) in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The chemical composition and antioxidant screening of the test feeds were carried out using standard techniques. Administration of the test feeds for 21 days to the diabetic rats of groups 4 and 5, resulted in 58.75% and 38.13% decreases in hyperglycemia and amelioration of their elevated urinary protein, glucose, SPGR, and relative kidney weights. The diabetic rats administered cocoyam incorporated feeds, had 2.71% and 19.52% increases in weight and growth rates, the diabetic rats administered unripe plantain incorporated feeds had 5.12% and 29.52% decreases in weight and growth rates while the diabetic control rats had 28.69%, 29.46%, 248.9% and 250.14% decreases in weights and growth rates. The cocoyam incorporated feeds contained higher antioxidants, minerals and phytochemicals except alkaloids than unripe plantain feed. Cocoyam and unripe plantain could be useful in the management of diabetic nephropathy.

Body weight homeostat that regulates fat mass independently of leptin in rats and mice

PubMed Central

Jansson, John-Olov; Hägg, Daniel A.; Schéle, Erik; Dickson, Suzanne L.; Anesten, Fredrik; Bake, Tina; Montelius, Mikael; Bellman, Jakob; Johansson, Maria E.; Cone, Roger D.; Drucker, Daniel J.; Wu, Jianyao; Aleksic, Biljana; Törnqvist, Anna E.; Sjögren, Klara; Gustafsson, Jan-Åke; Windahl, Sara H.; Ohlsson, Claes

2018-01-01

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat (“gravitostat”) that regulates fat mass. PMID:29279372

Perchlorate-induced combustion of organic matter with variable molecular weights: Implications for Mars missions

NASA Astrophysics Data System (ADS)

Sephton, Mark A.; Lewis, James M. T.; Watson, Jonathan S.; Montgomery, Wren; Garnier, Carole

2014-11-01

Instruments on the Viking landers and Curiosity rover analyzed samples of Mars and detected carbon dioxide and organic compounds of uncertain origin. Mineral-assisted reactions are leading to uncertainty, particularly those involving perchlorate minerals which thermally decompose to produce chlorine and oxygen which can then react with organic matter to generate organochlorine compounds and carbon dioxide. Although generally considered a problem for interpretation, the release profiles of generated gases can indicate the type of organic matter present. We have performed a set of experiments with perchlorate and organic matter of variable molecular weights. Results indicate that organic susceptibility to thermal degradation and mineral-assisted reactions is related to molecular weight. Low molecular weight organic matter reacts at lower temperatures than its high molecular weight counterparts. The natural occurrence and association of organic matter with differing molecular weights helps to discriminate between contamination (usually low molecular weight organic matter only) and indigenous carbon (commonly low and high molecular weight organic matter together). Our results can be used to provide insights into data returning from Mars.

Efficacy of lifestyle modification for long-term weight control.

PubMed

Wadden, Thomas A; Butryn, Meghan L; Byrne, Kirstin J

2004-12-01

A comprehensive program of lifestyle modification induces loss of approximately 10% of initial weight in 16 to 26 weeks, as revealed by a review of recent randomized controlled trials, including the Diabetes Prevention Program. Long-term weight control is facilitated by continued patient-therapist contact, whether provided in person or by telephone, mail, or e-mail. High levels of physical activity and the consumption of low-calorie, portion-controlled meals, including liquid meal replacements, can also help maintain weight loss. Additional studies are needed of the effects of macronutrient content (e.g., low-fat vs. low-carbohydrate diets) on long-term changes in weight and health. Research also is needed on effective methods of providing comprehensive weight loss control to the millions of Americans who need it.

The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus.

PubMed

Check, J H; Weidner, J

2015-01-01

To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema.

Sweet taste preferences before and after an intensive medical weight loss intervention.

PubMed

Asao, K; Rothberg, A E; Arcori, L; Kaur, M; Fowler, C E; Herman, W H

2016-06-01

Medical weight loss could change sweet taste threshold and preferences. The decrease in sweet taste preferences may, in turn, help in the maintenance of weight loss. This study examined the association between sweet taste preferences at baseline and weight change during a medical weight management programme and the impact of diet-induced weight loss on sweet taste preferences. Adult patients with body mass index ≥32 kg m -2 were recruited from a medical weight management clinic. Sweet taste preference was assessed using a forced-choice, paired-comparison tracking method before and after a very-low-calorie diet (VLCD). Twenty participants were included in the analysis: mean age was 53.1 (standard deviation [SD]: 11.4) years, and 14 were female. The mean body mass index was 41.4 (SD: 7.5) kg m -2 . The median preferred sucrose concentration before VLCD was 0.45 M. Following VLCD, mean change in weight was -13.3 (SD: 6.6) kg, and percentage weight change was -11.3% (SD: 5.9%). Based on mixed models with and without adjustment for demographic factors, diabetes status and smoking history, preferred sucrose concentration at baseline did not predict change in longer-term body weight. The change of preferred sucrose concentration following 12 weeks of VLCD was not significant ( P -value 0.95). Change in weight during and after VLCD was not associated with sweet taste preferences at baseline. After diet-induced weight loss, sweet taste preferences did not change.

Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM.

PubMed

Ma, Junfeng; Sanda, Miloslav; Wei, Renhuizi; Zhang, Lihua; Goldman, Radoslav

2018-02-07

Aberrant core fucosylation of proteins has been linked to liver diseases. In this study, we carried out multiple reaction monitoring (MRM) quantification of core fucosylated N-glycopeptides of serum proteins partially deglycosylated by a combination of endoglycosidases (endoF1, endoF2, and endoF3). To minimize variability associated with the preparatory steps, the analysis was performed without enrichment of glycopeptides or fractionation of serum besides the nanoRP chromatography. Specifically, we quantified core fucosylation of 22 N-glycopeptides derived from 17 proteins together with protein abundance of these glycoproteins in a cohort of 45 participants (15 disease-free control, 15 fibrosis and 15 cirrhosis patients) using a multiplex nanoUPLC-MS-MRM workflow. We find increased core fucosylation of 5 glycopeptides at the stage of liver fibrosis (i.e., N630 of serotransferrin, N107 of alpha-1-antitrypsin, N253 of plasma protease C1 inhibitor, N397 of ceruloplasmin, and N86 of vitronectin), increase of additional 6 glycopeptides at the stage of cirrhosis (i.e., N138 and N762 of ceruloplasmin, N354 of clusterin, N187 of hemopexin, N71 of immunoglobulin J chain, and N127 of lumican), while the degree of core fucosylation of 10 glycopeptides did not change. Interestingly, although we observe an increase in the core fucosylation at N86 of vitronectin in liver fibrosis, core fucosylation decreases on the N169 glycopeptide of the same protein. Our results demonstrate that the changes in core fucosylation are protein and site specific during the progression of fibrotic liver disease and independent of the changes in the quantity of N-glycoproteins. It is expected that the fully optimized multiplex LC-MS-MRM assay of core fucosylated glycopeptides will be useful for the serologic assessment of the fibrosis of liver. We have quantified the difference in core fucosylation among three comparison groups (healthy control, fibrosis and cirrhosis patients) using a sensitive and

Identification of Poly-N-Acetyllactosamine-Carrying Glycoproteins from HL-60 Human Promyelocytic Leukemia Cells Using a Site-Specific Glycome Analysis Method, Glyco-RIDGE

NASA Astrophysics Data System (ADS)

Togayachi, Akira; Tomioka, Azusa; Fujita, Mika; Sukegawa, Masako; Noro, Erika; Takakura, Daisuke; Miyazaki, Michiyo; Shikanai, Toshihide; Narimatsu, Hisashi; Kaji, Hiroyuki

2018-04-01

To elucidate the relationship between the protein function and the diversity and heterogeneity of glycans conjugated to the protein, glycosylation sites, glycan variation, and glycan proportions at each site of the glycoprotein must be analyzed. Glycopeptide-based structural analysis technology using mass spectrometry has been developed; however, complicated analyses of complex spectra obtained by multistage fragmentation are necessary, and sensitivity and throughput of the analyses are low. Therefore, we developed a liquid chromatography/mass spectrometry (MS)-based glycopeptide analysis method to reveal the site-specific glycome (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile, Glyco-RIDGE). This method used accurate masses and retention times of glycopeptides, without requiring MS2, and could be applied to complex mixtures. To increase the number of identified peptide, fractionation of sample glycopeptides for reduction of sample complexity is required. Therefore, in this study, glycopeptides were fractionated into four fractions by hydrophilic interaction chromatography, and each fraction was analyzed using the Glyco-RIDGE method. As a result, many glycopeptides having long glycans were enriched in the highest hydrophilic fraction. Based on the monosaccharide composition, these glycans were thought to be poly-N-acetyllactosamine (polylactosamine [pLN]), and 31 pLN-carrier proteins were identified in HL-60 cells. Gene ontology enrichment analysis revealed that pLN carriers included many molecules related to signal transduction, receptors, and cell adhesion. Thus, these findings provided important insights into the analysis of the glycoproteome using our novel Glyco-RIDGE method. [Figure not available: see fulltext.

Periodontal infection with Porphyromonas gingivalis induces preterm birth and lower birth weight in rats.

PubMed

Liang, Shanshan; Ren, Hongyu; Guo, Haiying; Xing, Wenyan; Liu, Chang; Ji, Yaoting; Jiang, Han; Zhang, Ping; Du, Minquan

2018-05-13

Preterm birth (PTB), accompanied by low birth weight (LBW) or not, is a syndrome with tremendous risk factors and long-term health consequences for children. In recent decades, overwhelming studies have shown that periodontitis contributes to prematurity and LBW. This study was conducted to determine the link between maternal periodontitis and the pathogenesis of PTB and/or LBW through a rat infection model induced by Porphyromonas gingivalis, an important periodontopathic bacterium. The murine model was established by surgically ligating the left mandibular 1 st molars and inoculating with P. gingivalis, and then all female rats initiated mating 6 weeks post-infection. The gestational day and birth weight were recorded, and blood, amniotic fluid and placental specimens were collected. Rats with a PTB and LBW newborns were observed in the P. gingivalis-infected group. Additionally, P. gingivalis infection significantly increased the maternal serum levels of interferon (IFN)-γ and interleukin (IL)-1β, whereas no significant difference in the cytokine response was observed in the amniotic fluid. Moreover, with the translocation of P. gingivalis to placentas, remarkable changes in gestational tissues were found, followed by significantly enhanced expression of Toll-like receptor 2 (TLR2) as well as Fas and Fas ligand (FasL). These results support the concept that severe cases of periodontitis by P. gingivalis infection may be indicative of rats being more susceptible to PTB/LBW, probably through the activation of the TLR2 and Fas/FasL pathways within the placental tissues. This study gave us new insight into how maternal periodontopathogens might be linked to placental damage and premature pathogenesis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Simultaneous Glycan-Peptide Characterization Using Hydrophilic Interaction Chromatography and Parallel Fragmentation by CID, Higher Energy Collisional Dissociation, and Electron Transfer Dissociation MS Applied to the N-Linked Glycoproteome of Campylobacter jejuni*

PubMed Central

Scott, Nichollas E.; Parker, Benjamin L.; Connolly, Angela M.; Paulech, Jana; Edwards, Alistair V. G.; Crossett, Ben; Falconer, Linda; Kolarich, Daniel; Djordjevic, Steven P.; Højrup, Peter; Packer, Nicolle H.; Larsen, Martin R.; Cordwell, Stuart J.

2011-01-01

Campylobacter jejuni is a gastrointestinal pathogen that is able to modify membrane and periplasmic proteins by the N-linked addition of a 7-residue glycan at the strict attachment motif (D/E)XNX(S/T). Strategies for a comprehensive analysis of the targets of glycosylation, however, are hampered by the resistance of the glycan-peptide bond to enzymatic digestion or β-elimination and have previously concentrated on soluble glycoproteins compatible with lectin affinity and gel-based approaches. We developed strategies for enriching C. jejuni HB93-13 glycopeptides using zwitterionic hydrophilic interaction chromatography and examined novel fragmentation, including collision-induced dissociation (CID) and higher energy collisional (C-trap) dissociation (HCD) as well as CID/electron transfer dissociation (ETD) mass spectrometry. CID/HCD enabled the identification of glycan structure and peptide backbone, allowing glycopeptide identification, whereas CID/ETD enabled the elucidation of glycosylation sites by maintaining the glycan-peptide linkage. A total of 130 glycopeptides, representing 75 glycosylation sites, were identified from LC-MS/MS using zwitterionic hydrophilic interaction chromatography coupled to CID/HCD and CID/ETD. CID/HCD provided the majority of the identifications (73 sites) compared with ETD (26 sites). We also examined soluble glycoproteins by soybean agglutinin affinity and two-dimensional electrophoresis and identified a further six glycosylation sites. This study more than doubles the number of confirmed N-linked glycosylation sites in C. jejuni and is the first to utilize HCD fragmentation for glycopeptide identification with intact glycan. We also show that hydrophobic integral membrane proteins are significant targets of glycosylation in this organism. Our data demonstrate that peptide-centric approaches coupled to novel mass spectrometric fragmentation techniques may be suitable for application to eukaryotic glycoproteins for simultaneous

Simultaneous glycan-peptide characterization using hydrophilic interaction chromatography and parallel fragmentation by CID, higher energy collisional dissociation, and electron transfer dissociation MS applied to the N-linked glycoproteome of Campylobacter jejuni.

PubMed

Scott, Nichollas E; Parker, Benjamin L; Connolly, Angela M; Paulech, Jana; Edwards, Alistair V G; Crossett, Ben; Falconer, Linda; Kolarich, Daniel; Djordjevic, Steven P; Højrup, Peter; Packer, Nicolle H; Larsen, Martin R; Cordwell, Stuart J

2011-02-01

Campylobacter jejuni is a gastrointestinal pathogen that is able to modify membrane and periplasmic proteins by the N-linked addition of a 7-residue glycan at the strict attachment motif (D/E)XNX(S/T). Strategies for a comprehensive analysis of the targets of glycosylation, however, are hampered by the resistance of the glycan-peptide bond to enzymatic digestion or β-elimination and have previously concentrated on soluble glycoproteins compatible with lectin affinity and gel-based approaches. We developed strategies for enriching C. jejuni HB93-13 glycopeptides using zwitterionic hydrophilic interaction chromatography and examined novel fragmentation, including collision-induced dissociation (CID) and higher energy collisional (C-trap) dissociation (HCD) as well as CID/electron transfer dissociation (ETD) mass spectrometry. CID/HCD enabled the identification of glycan structure and peptide backbone, allowing glycopeptide identification, whereas CID/ETD enabled the elucidation of glycosylation sites by maintaining the glycan-peptide linkage. A total of 130 glycopeptides, representing 75 glycosylation sites, were identified from LC-MS/MS using zwitterionic hydrophilic interaction chromatography coupled to CID/HCD and CID/ETD. CID/HCD provided the majority of the identifications (73 sites) compared with ETD (26 sites). We also examined soluble glycoproteins by soybean agglutinin affinity and two-dimensional electrophoresis and identified a further six glycosylation sites. This study more than doubles the number of confirmed N-linked glycosylation sites in C. jejuni and is the first to utilize HCD fragmentation for glycopeptide identification with intact glycan. We also show that hydrophobic integral membrane proteins are significant targets of glycosylation in this organism. Our data demonstrate that peptide-centric approaches coupled to novel mass spectrometric fragmentation techniques may be suitable for application to eukaryotic glycoproteins for simultaneous

Influence of Body Weight on Bone Mass, Architecture, and Turnover

PubMed Central

Iwaniec, Urszula T.; Turner, Russell T.

2016-01-01

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

Effect of Sulfation and Molecular Weight on Anticoagulant Activity of Dextran.

PubMed

Drozd, N N; Logvinova, Yu S; Torlopov, M A; Udoratina, E V

2017-02-01

Sulfation (to 2.8) of dextrans with molecular weight of 150 and 20 kDa was followed by the appearance of anticoagulant activity that increased with decreasing their molecular weight and did not depend on antithrombin, plasma inhibitor of serine proteases of the blood coagulation system. Antithrombin activity of dextran sulfate with a molecular weight of 20 kDa reached 12.6-15.3 U/mg. Dextran sulfates with molecular weights of 20 and 150 kDa did not potentiate ADP-induced human platelet aggregation.

Iatrogenic Subclinical Hyperthyroidism Does Not Promote Weight Loss.

PubMed

Kedia, Rohit; Lowes, Alicia; Gillis, Sarah; Markert, Ronald; Koroscil, Thomas

2016-02-01

Among patients who have undergone total thyroidectomy, do those with thyroid cancer being kept iatrogenically subclinical hyperthyroid (SCH) differ from euthyroid patients in long-term weight change? In a retrospective study, medical records identified 291 patients who had undergone a thyroidectomy for differentiated thyroid cancer or benign thyroid disease. Weight, thyroid-stimulating hormone, and levothyroxine dose were measured presurgery and 1, 2, and 3 years postsurgery. Of 291 patients, 147 were in the SCH group and 144 were in the euthyroid group. At all 3 years both groups gained weight from baseline, but the two groups did not differ in weight change from baseline at any time period: year 1 (SCH mean 0.4% ± 6.2% weight gain vs euthyroid group mean 2.2% ± 6.6% weight gain; P = 0.12), year 2 (SCH mean 1.1% ± 9.1% weight gain vs euthyroid mean 2.9% ± 7.8% weight gain; P = 0.22), and year 3 (SCH mean 2.6% ± 9.2% weight gain vs euthyroid mean 3.1% ± 11.1% weight gain; P = 0.49). Among total thyroidectomy patients, weight change did not differ between SCH patients and euthyroid patients at years 1 through 3. As such, the use of levothyroxine to induce SCH did not lead to long-term weight change when compared with euthyroid patients.

Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study.

PubMed

Liu, Gang; Dhana, Klodian; Furtado, Jeremy D; Rood, Jennifer; Zong, Geng; Liang, Liming; Qi, Lu; Bray, George A; DeJonge, Lilian; Coull, Brent; Grandjean, Philippe; Sun, Qi

2018-02-01

The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30-70 years. Body weight was measured at baseline and 6, 12, 18, and 24 months. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6-24 months (weight regain period). After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. In women, comparing the highest to the lowest tertiles of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) (Ptrend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) (Ptrend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) (Ptrend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) (Ptrend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) (Ptrend = 0.03). When further adjusted for changes in body

Body weight gain induced by a newer antipsychotic agent reversed as negative symptoms improved.

PubMed

Koga, M; Nakayama, K

2005-07-01

We describe a patient in whom improvement in negative symptoms contributed to early weight loss and subsequent long-term improvement in weight management. Case report. A 26-year-old woman with schizophrenia gained 7 kg over the course of 1 year after starting treatment with olanzapine. However, as negative symptoms gradually improved with treatment, she became motivated to diet and exercise regularly. She quickly lost 9 kg and subsequently maintained optimal weight (55 kg; body mass index, 24.1 kg/m(2) ). Important strategies for minimizing weight gain in patients taking antipsychotic agents include improving negative symptoms of avolition and apathy, regular monitoring of body weight and potential medical consequences of overweight and obesity, and educating the patient about the importance of diet and regular exercise.

Protein-induced satiety: effects and mechanisms of different proteins.

PubMed

Veldhorst, M; Smeets, A; Soenen, S; Hochstenbach-Waelen, A; Hursel, R; Diepvens, K; Lejeune, M; Luscombe-Marsh, N; Westerterp-Plantenga, M

2008-05-23

Relatively high protein diets, i.e. diets that maintain the absolute number of grams of protein ingested as compared to before dieting, are a popular strategy for weight loss and weight maintenance. Research into multiple mechanisms regulating body weight has focused on the effects of different quantities and types of dietary protein. Satiety and energy expenditure are important in protein-enhanced weight loss and weight maintenance. Protein-induced satiety has been shown acutely, with single meals, with contents of 25% to 81% of energy from protein in general or from specific proteins, while subsequent energy intake reduction was significant. Protein-induced satiety has been shown with high protein ad libitum diets, lasting from 1 to 6 days, up to 6 months. Also significantly greater weight loss has been observed in comparison with control. Mechanisms explaining protein-induced satiety are nutrient-specific, and consist mainly of synchronization with elevated amino acid concentrations. Different proteins cause different nutrient related responses of (an)orexigenic hormones. Protein-induced satiety coincides with a relatively high GLP-1 release, stimulated by the carbohydrate content of the diet, PYY release, while ghrelin does not seem to be especially affected, and little information is available on CCK. Protein-induced satiety is related to protein-induced energy expenditure. Finally, protein-induced satiety appears to be of vital importance for weight loss and weight maintenance. With respect to possible adverse events, chronic ingestion of large amounts of sulphur-containing amino acids may have an indirect effect on blood pressure by induction of renal subtle structural damage, ultimately leading to loss of nephron mass, and a secondary increase in blood pressure. The established synergy between obesity and low nephron number on induction of high blood pressure and further decline of renal function identifies subjects with obesity, metabolic syndrome and

Two models for weight gain and hyperphagia as side effects of atypical antipsychotics in male rats: validation with olanzapine and ziprasidone.

PubMed

Shobo, Miwako; Yamada, Hiroshi; Mihara, Takuma; Kondo, Yuji; Irie, Megumi; Harada, Katsuya; Ni, Keni; Matsuoka, Nobuya; Kayama, Yukihiko

2011-01-20

Body weight gain is one of the most serious side effects associated with clinical use of antipsychotics. However, the mechanisms by which antipsychotics induce body weight gain are unknown, and no reliable animal models of antipsychotics-induced weight gain have been established. The present studies were designed to establish male rat models of weight gain induced by chronic and acute treatment with antipsychotics. Six-week chronic treatment with olanzapine (5, 7.5, and 10mg/kg/day) in male Sprague-Dawley rats fed a daily diet resembling a human macronutrient diet, significantly increased body weight gain and weight of fatty tissues. In contrast, ziprasidone (1.25, 2.5, and 5mg/kg/day) administration caused no observable adverse effects. We then investigated feeding behavior with acute antipsychotic treatment in male rats using an automated food measurement apparatus. Rats were allowed restricted access to normal laboratory chow (4h/day). With acute olanzapine (0.5, 1, and 2mg/kg, i.p.) treatment in the light phase, food intake volume and duration were significantly increased, while treatment with ziprasidone (0.3, 1, and 3mg/kg, i.p.) did not increase food intake volume or meal time duration. Findings from the present studies showed that chronic treatment with olanzapine in male rats induced body weight gain, and acute injection induced hyperphagia, suggesting that hyperphagia may be involved in the weight gain and obesity-inducing properties of chronically administered olanzapine. These animal models may provide useful experimental platforms for analysis of the mechanism of hyperphagia and evaluating the potential risk of novel antipsychotics to induce weight gain in humans. Copyright © 2010 Elsevier B.V. All rights reserved.

Weight loss without losing muscle mass in pre-obese and obese subjects induced by a high-soy-protein diet.

PubMed

Deibert, P; König, D; Schmidt-Trucksaess, A; Zaenker, K S; Frey, I; Landmann, U; Berg, A

2004-10-01

To determine change of weight, body composition, metabolic and hormonal parameters induced by different intervention protocols. Randomized, controlled study including participants exhibiting a BMI between 27.5 and 35. Three different interventions containing lifestyle education (LE-G), or a substitutional diet containing a high-soy-protein low-fat diet with (SD/PA-G) or without (SD-G) a guided physical activity program. A total of 90 subjects (mean weight 89.9 kg; mean BMI 31.5), randomly assigned to one of three treatment groups. Change in body weight, fat mass and lean body mass measured with the Bod Pod device at baseline, 6 weeks and 6 months; change in metabolic and hormonal parameters. In all, 83 subjects completed the 6-months study. BMI dropped highly significantly in all groups (LE-G: -2.2+/-1.43 kg/m(2); SD-G: -3.1+/-1.29 kg/m(2); SD/PA-G: -3.0+/-1.29 kg/m(2)). Subjects in the SD-G and in the SD/PA-G lost more weight during the 6-months study (-8.9+/-3.9; -8.9+/-3.9 kg) than did those in the LE-G (-6.2+/-4.2 kg), and had a greater decrease in fat mass (-8.8+/-4.27; -9.4+/-4.54 kg) than those in the LE-G (-6.6+/-4.59 kg). In contrast, no significant intraindividual or between-group changes in the fat-free mass were seen. In all groups, metabolic parameters showed an improvement in glycemic control and lipid profile. Our data suggest that a high-soy-protein and low-fat diet can improve the body composition in overweight and obese people, losing fat but preserving muscle mass.

Weight-ing: the experience of waiting on weight loss.

PubMed

Glenn, Nicole M

2013-03-01

Perhaps we want to be perfect, strive for health, beauty, and the admiring gaze of others. Maybe we desire the body of our youth, the "healthy" body, the body that has just the right fit. Regardless of the motivation, we might find ourselves striving, wanting, and waiting on weight loss. What is it to wait on weight loss? I explore the meaning of this experience-as-lived using van Manen's guide to phenomenological reflection and writing. Weight has become an increasing focus of contemporary culture, demonstrated, for example, by a growing weight-loss industry and global obesity "epidemic." Weight has become synonymous with health status, and weight loss with "healthier." I examine the weight wait through experiences of the common and uncommon, considering relations to time, body, space, and the other with the aim of evoking a felt, embodied, emotive understanding of the meaning of waiting on weight loss. I also discuss the implications of the findings.

Rcan2 and estradiol independently regulate body weight in female mice

PubMed Central

Ding, Ling-Cui; Gong, Qian-Qian; Li, Shi-Wei; Fu, Xiao-Long; Jin, Ye-Cheng; Zhang, Jian; Gao, Jian-Gang; Sun, Xiao-Yang

2017-01-01

Rcan2 increases food intake and plays an important role in the development of age- and diet- induced obesity in male mice. However, in females, wild-type mice grow almost at a similar rate as Rcan2−/− mice on normal chow diet from 6 weeks of age. Here we showed that the ability of Rcan2 to promote weight gain was attenuated by energy expenditure mediated by 17β-estradiol in female mice. Using ovariectomy-operated models, we found that 17β-estradiol deprivation did not alter food intake, but induced more weight gain in wild-type mice than Rcan2−/− mice. If wild-type mice ingested equally as Rcan2−/− mice, in the same ovarian state they exhibited similar weight changes, but the mice in ovariectomized groups were significantly heavier than the ovarian-intact mice, suggesting that body weight is not only regulated by Rcan2, but also by 17β-estradiol. Furthermore, we demonstrated that Rcan2 and 17β-estradiol independently regulated body weight even on high-fat diets. Therefore, our findings indicate that Rcan2 and 17β-estradiol regulate body weight through different mechanisms. Rcan2 increases food intake, whereas 17β-estradiol promotes energy expenditure. These findings provide novel insights into the sexual dimorphism of body weight regulation. PMID:28624805

Macrophage Integrins Modulate Response to Ultra-High Molecular Weight Polyethylene Particles and Direct Particle-Induced Osteolysis

PubMed Central

Zaveri, Toral D.; Dolgova, Natalia V.; Lewis, Jamal S.; Hamaker, Kiri; Clare-Salzler, Michael J.; Keselowsky, Benjamin G.

2016-01-01

Aseptic loosening due to peri-prosthetic osteolysis is one of the primary causes for failure of artificial joint replacements. Implant-derived wear particles, often ultra-high molecular weight polyethylene (UHMWPE) microparticles, initiate an inflammatory cascade upon phagocytosis by macrophages, which leads to osteoclast recruitment and activation, ultimately resulting in osteolysis. Investigation into integrin receptors, involved in cellular interactions with biomaterial-adsorbed adhesive proteins, is of interest to understand and modulate inflammatory processes. In this work, we investigate the role of macrophage integrins Mac-1 and RGD-binding integrins in response to UHMWPE wear particles. Using integrin knockout mice as well as integrin blocking techniques, reduction in macrophage phagocytosis and inflammatory cytokine secretion is demonstrated when these receptors are either absent or blocked. Along this line, various opsonizing proteins are shown to differentially modulate microparticle uptake and macrophage secretion of inflammatory cytokines. Furthermore, using a calvarial osteolysis model it is demonstrated that both Mac-1 integrin and RGD-binding integrins modulate the particle induced osteolysis response to UHMWPE microparticles, with a 40% decrease in the area of osteolysis by the absence or blocking of these integrins, in vivo. Altogether, these findings indicate Mac-1 and RGD-binding integrins are involved in macrophage-directed inflammatory responses to UHMWPE and may serve as therapeutic targets to mitigate wear particle induced peri-prosthetic osteolysis for improved performance of implanted joints. PMID:27889664

Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Testylier, Guy; Lahrech, Hana; Universite Joseph Fourier, Grenoble, F-38043

2007-04-15

Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 {mu}g/kg), the mice were anesthetized with an isoflurane/N{sub 2}O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication andmore » was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into Brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures.« less

Diet-induced loss of cyclic ovarian function at normal body weight in a rodent model for bulimia nervosa.

PubMed

Leigh, A J; Stock, M J; Lacey, J H; Wilson, C A

1998-03-01

A bulimic rat model was used to test whether type and frequency of food intake mimicking that in human bulimia nervosa could disrupt oestrous cyclicity, induce an effect on glycoprotein (LH) structure, or affect both processes and if so, to determine whether any such effects were acute, or persisted after return to normal eating patterns. Voluntary hyperphagia was induced by offering female rats a varied and palatable choice of human food items--the 'cafeteria diet'. There were four groups: control (normal chow), obese (continuous cafeteria diet), post-obese (cafeteria diet, then fasted to reduce weight to that of controls) and binge (cafeteria alternated with normal diet every few days). Animals were maintained on these diets for 60 days (phase I). They were then given a GnRH challenge on day 2 of dioestrus of the cycle. Twenty-four hours later, half of the animals in each group were killed for assessment of effects on their reproductive organs. The remaining animals were returned to normal diets and kept for a further 40 days, when the GnRH challenge was repeated and the animals were killed 24 h later (phase II). All animals on the cafeteria diet in phase I exhibited significant disruption of oestrous cyclicity irrespective of body weight. LH released in response to the first GnRH challenge showed a prolonged half-life, and/or increased rate of secretion in the obese and post-obese groups but in the binge group the secretory/clearance properties resembled those of control animals. After the second GnRH challenge at the end of phase II, however, the LH of the binge group appeared to have different secretory or clearance characteristics, whereas that of the previously obese animals had returned to normal. These data show ovarian cyclicity was disrupted by hyperphagia and irregular eating, even at normal body weight. Relating ovarian function to pituitary output in terms of LH, the effects of the continuous cafeteria diet did not appear to persist in the animals

Dynamics of intrapericardial and extrapericardial fat tissues during long-term, dietary-induced, moderate weight loss.

PubMed

Tsaban, Gal; Wolak, Arik; Avni-Hassid, Hila; Gepner, Yftach; Shelef, Ilan; Henkin, Yaakov; Schwarzfuchs, Dan; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Tene, Lilac; Zelicha, Hila; Yaskolka-Meir, Anat; Komy, Oded; Bilitzky, Avital; Chassidim, Yoash; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Thiery, Joachim; Dicker, Dror; Rudich, Assaf; Stampfer, Meir J; Shai, Iris

2017-10-01

) cholesterol (β = 2.689; 95% CI: 0.373, 5.003; P = 0.024), and the EPF relative reduction was associated with an increase in HDL cholesterol (β = -0.452; 95% CI: -0.880, -0.023; P = 0.039) and a decrease in total cholesterol and HDL cholesterol (β = 3.766; 95% CI: 1.092, 6.440; P = 0.007). Conclusions: Moderate but persistent dietary-induced weight loss substantially decreased both IPF and EPF volumes. Reduction of pericardial adipose tissues is independently associated with an improved lipid profile. The Mediterranean diet, rich in unsaturated fats and restricted carbohydrates, is superior to an LF diet in terms of the IPF burden reduction. This trial was registered at clinicaltrials.gov as NCT01530724. © 2017 American Society for Nutrition.

Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats

PubMed Central

Adam, Clare L.; Gratz, Silvia W.; Peinado, Diana I.; Thomson, Lynn M.; Garden, Karen E.; Williams, Patricia A.; Richardson, Anthony J.; Ross, Alexander W.

2016-01-01

Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity. PMID:27224646

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats.

PubMed

Samat, Suhana; Kanyan Enchang, Francis; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani

2017-01-01

Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

PubMed Central

Kanyan Enchang, Francis; Nor Hussein, Fuzina

2017-01-01

Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat. PMID:28246535

Immunostimulative Activity of Low Molecular Weight Chitosans in RAW264.7 Macrophages

PubMed Central

Wu, Ning; Wen, Zheng-Shun; Xiang, Xing-Wei; Huang, Yan-Na; Gao, Yang; Qu, You-Le

2015-01-01

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been reported to exert many biological activities, such as antioxidant and antitumor effects. However, complex and molecular weight dependent effects of chitosan remain controversial and the mechanisms that mediate these complex effects are still poorly defined. This study was carried out to investigate the immunostimulative effect of different molecular weight chitosan in RAW264.7 macrophages. Our data suggested that two LMWCs (molecular weight of 3 kDa and 50 kDa) both possessed immunostimulative activity, which was dependent on dose and, at the higher doses, also on the molecular weight. LMWCs could significantly enhance the the pinocytic activity, and induce the production of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon-γ (IFN-γ), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in a molecular weight and concentration-dependent manner. LMWCs were further showed to promote the expression of the genes including iNOS, TNF-α. Taken together, our findings suggested that LMWCs elicited significantly immunomodulatory response through up-regulating mRNA expression of proinflammatory cytokines and activated RAW264.7 macrophage in a molecular weight- and concentration-dependent manner. PMID:26437419

Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity.

PubMed

Kim, Jongwan; Yun, Eun-Young; Quan, Fu-Shi; Park, Seung-Won; Goo, Tae-Won

2017-01-01

The α -glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS).

Preoperative weight loss with glucagon-like peptide-1 receptor agonist treatment predicts greater weight loss achieved by the combination of medical weight management and bariatric surgery in patients with type 2 diabetes: A longitudinal analysis.

PubMed

Tang, Tien; Abbott, Sally; le Roux, Carel W; Wilson, Violet; Singhal, Rishi; Bellary, Srikanth; Tahrani, Abd A

2018-03-01

We examined the relationship between weight changes after preoperative glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment and weight changes from the start of medical weight management (MWM) until 12 months after bariatric surgery in patients with type 2 diabetes in a retrospective cohort study. A total of 45 patients (64.4% women, median [interquartile range] age 49 [45-60] years) were included. The median (interquartile range) weight loss from start of MWM until 12 months post-surgery was 17.9% (13.0%-29.3%). GLP-1RA treatment during MWM resulted in 5.0% (1.9%-7.7%) weight loss. Weight loss during GLP-1RA treatment predicted weight loss from the start of MWM until 12 months post-surgery, but not postoperative weight loss after adjustment. The proportion of weight loss from start of MWM to 12 months post-surgery attributed to GLP-1RA treatment was negatively associated with that attributed to surgery, after adjustment. In conclusion, weight change after GLP-1RA treatment predicted the weight loss achieved by a combination of MWM and bariatric surgery, but not weight loss induced by surgery only. Failure to lose weight after GLP-1RA treatment should not be considered a barrier to undergoing bariatric surgery. © 2017 John Wiley & Sons Ltd.

Intermittent Fasting with or without Exercise Prevents Weight Gain and Improves Lipids in Diet-Induced Obese Mice.

PubMed

Wilson, Robin A; Deasy, William; Stathis, Christos G; Hayes, Alan; Cooke, Matthew B

2018-03-12

Intermittent fasting (IF) and high intensity interval training (HIIT) are effective lifestyle interventions for improving body composition and overall health. However, the long-term effects of IF and potential synergistic effects of combining IF with exercise are unclear. The purpose of the study was to investigate the long-term effects of IF, with or without HIIT, on body composition and markers of metabolic health in diet-induced obese mice. In a randosmised, controlled design, 8-week-old C57BL/6 mice (males ( n = 39) and females ( n = 49)) were fed a high fat (HF) and sugar (S) water diet (30% ( w / v )) for 24-weeks but were separated into five groups at 12-weeks: (1) 'obese' baseline control (OBC); (2) no intervention (CON); (3) intermittent fasting (IF); (4) high intensity intermittent exercise (HIIT) and (5) combination of dietary and exercise intervention (IF + HIIT). Body composition, strength and blood variables were measured at 0, 10 and/or 12-weeks. Intermittent fasting with or without HIIT resulted in significantly less weight gain, fat mass accumulation and reduced serum low density lipoproteins (LDL) levels compared to HIIT and CON male mice ( p < 0.05). The results suggest that IF, with or without HIIT, can be an effective strategy for weight gain prevention despite concurrently consuming a high fat and sugar diet.

Intermittent Fasting with or without Exercise Prevents Weight Gain and Improves Lipids in Diet-Induced Obese Mice

PubMed Central

Wilson, Robin A.; Deasy, William; Stathis, Christos G.; Hayes, Alan; Cooke, Matthew B.

2018-01-01

Intermittent fasting (IF) and high intensity interval training (HIIT) are effective lifestyle interventions for improving body composition and overall health. However, the long-term effects of IF and potential synergistic effects of combining IF with exercise are unclear. The purpose of the study was to investigate the long-term effects of IF, with or without HIIT, on body composition and markers of metabolic health in diet-induced obese mice. In a randosmised, controlled design, 8-week-old C57BL/6 mice (males (n = 39) and females (n = 49)) were fed a high fat (HF) and sugar (S) water diet (30% (w/v)) for 24-weeks but were separated into five groups at 12-weeks: (1) ‘obese’ baseline control (OBC); (2) no intervention (CON); (3) intermittent fasting (IF); (4) high intensity intermittent exercise (HIIT) and (5) combination of dietary and exercise intervention (IF + HIIT). Body composition, strength and blood variables were measured at 0, 10 and/or 12-weeks. Intermittent fasting with or without HIIT resulted in significantly less weight gain, fat mass accumulation and reduced serum low density lipoproteins (LDL) levels compared to HIIT and CON male mice (p < 0.05). The results suggest that IF, with or without HIIT, can be an effective strategy for weight gain prevention despite concurrently consuming a high fat and sugar diet. PMID:29534545

Renoprotective effect of low-molecular-weight sulfated polysaccharide from the seaweed Laminaria japonica on glycerol-induced acute kidney injury in rats.

PubMed

Li, Xinpeng; Wang, Jing; Zhang, Hong; Zhang, Quanbin

2017-02-01

We investigated the renal protective effect of low-molecular-weight sulfated polysaccharide (LMWSP) fractions extracted from Laminaria japonica on glycerol-induced acute kidney injury (AKI) in rats. Glycerol treatment significantly increased serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Intraperitoneal injection of LMWSP fractions markedly decreased SCr and BUN levels and reduced renal swelling. The fraction of 1.0M NaCl displayed the best renal protective effect of all fractions in attenuating AKI and maintaining blood glucose. Copyright © 2016 Elsevier B.V. All rights reserved.

Chili pepper as a body weight-loss food.

PubMed

Varghese, Sharon; Kubatka, Peter; Rodrigo, Luis; Gazdikova, Katarina; Caprnda, Martin; Fedotova, Julia; Zulli, Anthony; Kruzliak, Peter; Büsselberg, Dietrich

2017-06-01

Chili has culinary as well as medical importance. Studies in humans, using a wide range of doses of chili intake (varying from a single meal to a continuous uptake for up to 12 weeks), concluded that it facilitates weight loss. In regard to this, the main targets of chili are fat metabolism, energy expenditure, and thermogenesis. To induce weight loss, the active substance of chili, capsaicin, activates Transient Receptor Potential Cation Channel sub-family V member 1 (TRPV1) channels) receptors causing an increase in intracellular calcium levels and triggering the sympathetic nervous system. Apart from TRPV1, chili directly reduces energy expenditure by activating Brown Adipose Tissue. Weight loss by chili is also the result of an improved control of insulin, which supports weight management and has positive effects for treatment for diseases like obesity, diabetes and cardiovascular disorders. This review summarizes the major pathways by which chili contributes to ameliorating parameters that help weight management and how the consumption of chili can help in accelerating weight loss through dietary modifications.

Olanzapine causes hypothermia, inactivity, a deranged feeding pattern and weight gain in female Wistar rats.

PubMed

Evers, S S; Calcagnoli, F; van Dijk, G; Scheurink, A J W

2010-11-01

Olanzapine is an a-typical antipsychotic drug antagonizing predominantly 5-HT and dopamine, but also histamine, muscarin, and α-adrenergic receptors. In humans, Olanzapine induces weight gain and increases the risk of type 2 diabetes. The underlying mechanisms of Olanzapine-induced weight gain are unclear. To study this we administered Olanzapine (5mg/kg) in female Wistar rats on a medium fat diet for 14 days via a permanent gastric catheter twice a day, just prior to the onset and at the middle of dark phase. Food and water intake, locomotor activity and body temperature were measured. Olanzapine acutely induced hypothermia, markedly decreased locomotor activity and increased body weight during 14 days of treatment. Olanzapine treatment did not result in an alteration of 24h food intake, but diurnal patterns of feeding behavior and body temperature were dramatically changed. We conclude that in female Wistar rats Olanzapine has an acute hypothermic effect, that the effect of Olanzapine on feeding behavior is secondary to the effect on activity, and that Olanzapine-induced weight gain is primarily the result of reduction in locomotor activity. Copyright © 2010 Elsevier Inc. All rights reserved.

Qualitative descriptive study exploring schizophrenia and the everyday effect of medication-induced weight gain.

PubMed

Vandyk, Amanda Digel; Baker, Cynthia

2012-08-01

Weight gain and obesity are serious side effects of the medications used to manage psychotic disorders and successful, long-term weight loss interventions are not yet available. One reason for this may be that current interventions are designed without consideration of the patient's perspective. The purpose of this study was to explore the subjective experience of weight and lifestyle from the perspective of people with schizophrenia. A qualitative, constructivist research design was used and conversational interviews were conducted with 18 purposefully recruited participants from an outpatient clinic at a psychiatric hospital in Eastern Ontario. Data were analysed according to the method of constant comparison and three central themes emerged: a life altering diagnosis, weight management as complex, and today's experiences shape tomorrow's outcomes. Weight management was seen as difficult yet important to the participants. The findings of this study provide insight into the views and opinions of the participants regarding weight and lifestyle and may be used to support the design of tailored heath initiatives for persons with mental illness. © 2012 The Authors. International Journal of Mental Health Nursing © 2012 Australian College of Mental Health Nurses Inc.

Proteolytic fragmentation and peptide mapping of human carboxyamidomethylated tracheobronchial mucin.

PubMed

Rose, M C; Kaufman, B; Martin, B M

1989-05-15

Human tracheobronchial mucin was isolated from lung mucosal gel by chromatography on Sepharose 4B in the presence of dissociating and reducing agents, and its thiol residues were carboxyamidomethylated with iodo[1(-14)C]acetamide. The 14C-carboxyamido-methylated mucin was purified by chromatography on Sepharose 2B. No low molecular weight components were detected by molecular sieve chromatography or polyacrylamide gel electrophoresis in the presence of dissociating and reducing agents or by analytical density centrifugation in CsCl/guanidinium chloride. After digestion of the purified 14C-mucin with trypsin-L-1-tosylamido-2-phenylethyl chloromethyl ketone, three fractions (TR-1, TR-2, and TR-3) were observed by chromatography on Sepharose 4B. TR-1, a 260-kDa mucin glycopeptide fragment, contained all of the neutral hexose and blood group activity and 20% of the radioactivity in the undigested mucin. TR-1 was refractory to a second incubation with trypsin but could be digested by papain or Pronase to a smaller mucin glycopeptide fraction, as judged by the slight decrease in apparent molecular weight on Sepharose CL-4B. These mucin glycopeptides contained approximately 50% of the radioactivity in the TR-1 fraction, indicating that the glycosylated domains of carboxyamidomethylated tracheobronchial mucin contained thiol residues. The remainder of the radioactivity from papain or Pronase digests of TR-1 eluted, like the TR-3 fractions, in the salt fraction on Sepharose CL-4B. Peptide mapping of the nonglycosylated TR-3 fraction by TLC and high voltage electrophoresis yielded six principal and several less intensely stained ninhydrin reactive components, with the radiolabel concentrated in one of the latter peptides. Peptide purification of the TR-3 fraction by high pressure liquid chromatography on a C18 reverse phase column demonstrated the presence of four major peptides, with TR-3A being the dominant component. The TR-3D peptide contained S

Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study

PubMed Central

Furtado, Jeremy D.; Liang, Liming; Qi, Lu; Bray, George A.; DeJonge, Lilian; Coull, Brent

2018-01-01

Background The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. Methods and findings In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30–70 years. Body weight was measured at baseline and 6, 12, 18, and 24 months. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6–24 months (weight regain period). After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. In women, comparing the highest to the lowest tertiles of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) (Ptrend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) (Ptrend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) (Ptrend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) (Ptrend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) (Ptrend = 0.03). When

Coagulative interstitial laser-induced thermotherapy of benign prostatic hyperplasia: online imaging with a T2-weighted fast spin-echo MR sequence--experience in six patients.

PubMed

Mueller-Lisse, U G; Thoma, M; Faber, S; Heuck, A F; Muschter, R; Schneede, P; Weninger, E; Hofstetter, A G; Reiser, M F

1999-02-01

To determine if hypointense lesions clearly outline on T2-weighted fast spin-echo (SE) magnetic resonance (MR) images obtained during coagulative interstitial laser-induced thermotherapy (LITT) of a prostate with benign hyperplasia. In six patients with benign prostatic hyperplasia (BPH), 12 LITT treatments were followed online with repetitive axial T2-weighted fast SE imaging (repetition time, 3,700 msec; echo time, 138 msec; acquisition time, 19 seconds). Development, time course, correlation with interstitial tissue temperature, and diameters of hypointense lesions around the laser diffusor tip were investigated. Lesion diameters on T2-weighted images acquired during LITT were compared with diameters of final lesions on T2-weighted images and unperfused lesions on enhanced T1-weighted SE images obtained at the end of therapy. Hypointense lesions developed within 20-40 seconds of LITT. Average correlation coefficients between interstitial temperature development and signal intensity development were 0.92 during LITT and 0.90 after LITT. Regression slopes were significantly steeper during LITT (0.67% signal intensity change per degree Celsius) than after LITT (0.47% per degree Celsius; P = .038). Lesions remained visible after LITT for all procedures. Average maximum diameters of lesions were 1-3 mm larger during LITT than after LITT (P = .0006-.019). Repetitive T2-weighted fast SE MR imaging during interstitial coagulative LITT of BPH demonstrates the development of permanent hypointense prostate lesions. However, posttherapeutic lesion diameters tend to be overestimated during LITT.

Endoplasmic Reticulum Stress Induces Myostatin High Molecular Weight Aggregates and Impairs Mature Myostatin Secretion.

PubMed

Sachdev, Rishibha; Kappes-Horn, Karin; Paulsen, Lydia; Duernberger, Yvonne; Pleschka, Catharina; Denner, Philip; Kundu, Bishwajit; Reimann, Jens; Vorberg, Ina

2018-03-15

Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line. We find that increased MsntPP protein levels induce ER stress. MstnPP metabolites were predominantly retained within the endoplasmic reticulum (ER), also evident in sIBM histology. MstnPP cleavage products formed insoluble high molecular weight aggregates, a process that was aggravated by experimental ER stress. Importantly, ER stress also impaired secretion of mature myostatin. Reduced secretion and aggregation of MstnPP metabolites were not simply caused by overexpression, as both events were also observed in wildtype cells under ER stress. It is tempting to speculate that reduced circulating myostatin growth factor could be one explanation for the poor clinical efficacy of drugs targeting the myostatin pathway in sIBM.

[Streptozotocin-induced maternal intrauterine hyperglycemia environment and its influence on development and metabolic in adult offspring with high birth weight in rats].

PubMed

Li, Xin; Luo, Shu-jing; Zhang, Kai; Yang, Hui-xia

2012-10-01

To establish and assess the high-birth-weight offspring model of the diabetic rat induced by stueptozotocin, and the long-term metabolic impact of maternal hyperglycemia of those offsprings. Streptozotocin (STZ, 25 mg/kg) was given to Wistar rats (G group, n = 14) once intraperitoneally to induce maternal hyperglycemia model (blood glucose between 10 - 20 mmol/L), and there still had a number of rats defined as severe hyperglycemia model group (SG group, n = 5). The Control group (C group, n = 7) were given the same volume citrate buffer solution. The body weight and blood glucose were recorded, and the lavaging glucose tolerance test (LGTT) was performed by a glucose meter in the gestation. The offsprings were corresponding allocated into 2 groups, and the birth weight were recorded. All the offsprings were observated body weight, blood glucose blood pressure (male rats only), and so on. (1) The blood glucose of G group (16.8 ± 5.4 mmol/L) and SG group (20.5 ± 5.6 mmol/L) were increased significantly as compared with C group (7.0 ± 1.4 mmol/L) 5 days after the model was established (P < 0.01); and the average blood glucose of G group (16.6 ± 3.4 mmol/L) and SG group (23.8 ± 1.5 mmol/L) increased too as comparede with C group (5.8 ± 1.1 mmol/L), the difference was significance according to statistics (P < 0.01). (2) According to the LGTT result, which operationed on generation day 4 and day 10, the blood glucose of every time point of G group were increased significantly as compared with C group (P < 0.01). (3) The male and female birth weight of G group was remarkably higher than the C group and the SG group (P < 0.05), and the blood glucose of SG/G/C group was (6.5 ± 1.2) mmol/L, (4.1 ± 0.8) mmol/L, (4.1 ± 0.8) mmol/L respectively, according to the statistics results, the difference between SG group and G/C group respectively both remarkable (P < 0.05). (4) The body weight, Lee's index, fat weight, and the fat weight of mass ratio in C group mother rats

Mandatory weight loss during the wait for bariatric surgery.

PubMed

Glenn, Nicole M; Raine, Kim D; Spence, John C

2015-01-01

Mandatory presurgical, behavior-induced weight loss, although not standard, is a relatively common practice among bariatric surgical clinics. We explore the patient's experience of this practice using phenomenology. We gathered experiential accounts from 7 individuals waiting to have the procedure at a large publically funded clinic in western Canada. In writing this article, we focused on four phenomenological themes: "just nod your head and carry on"-silencing through the ideal; waiting and weighing-promoting weight consciousness to the weight conscious; paying for surgical approval through weight loss; and presurgical weight loss and questioning the need for weight loss surgery altogether. We contrast the experiential findings with the clinical literature to question the impact and possible (unintended or unexpected) effects the practice might have, particularly on patients' lives. We situate this article within a larger discussion about the possible contribution of experiential knowledge to clinical guidelines, practices, and pedagogies. © The Author(s) 2014.

Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells.

PubMed

Dun, Yun-lou; Zhou, Xiao-lin; Guan, Hua-shi; Yu, Guang-li; Li, Chun-xia; Hu, Ting; Zhao, Xia; Cheng, Xiao-lei; He, Xiao-xi; Hao, Jie-jie

2015-09-01

Muscle wasting is associated with a variety of chronic or inflammatory disorders. Evidence suggests that inflammatory cytokines play a vital role in muscle inflammatory pathology and this may result in oxidative damage and mitochondrial dysfunction in skeletal muscle. In our study, we used microwave degradation to prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells induced by tumor necrosis factor alpha (TNF-α), a cell inflammatory cytokine. The results indicated that LMG could alleviate mitochondrial reactive oxygen species (ROS) production, increase the activities of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential (MMP) and upregulate the expression of mitochondrial respiratory chain protein in TNF-α-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-α-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-κB) signaling pathway. These suggest that LMG is capable of protecting TNF-α-induced C2C12 cells against oxidative damage and mitochondrial dysfunction.

Maternal Prepregnancy Body Mass Index and Gestational Weight Gain on Pregnancy Outcomes

PubMed Central

Li, Nan; Liu, Enqing; Guo, Jia; Pan, Lei; Li, Baojuan; Wang, Ping; Liu, Jin; Wang, Yue; Liu, Gongshu; Baccarelli, Andrea A.; Hou, Lifang; Hu, Gang

2013-01-01

Objective The aim of the present study was to evaluate the single and joint associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Tianjin, China. Methods Between June 2009 and May 2011, health care records of 33,973 pregnant women were collected and their children were measured for birth weight and birth length. The independent and joint associations of prepregnancy BMI and GWG based on the Institute of Medicine (IOM) guidelines with the risks of pregnancy and neonatal outcomes were examined by using Logistic Regression. Results After adjustment for all confounding factors, maternal prepregnancy BMI was positively associated with risks of gestational diabetes mellitus (GDM), pregnancy-induced hypertension, caesarean delivery, preterm delivery, large-for-gestational age infant (LGA), and macrosomia, and inversely associated with risks of small-for-gestational age infant (SGA) and low birth weight. Maternal excessive GWG was associated with increased risks of pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia, and decreased risks of preterm delivery, SGA, and low birth weight. Maternal inadequate GWG was associated with increased risks of preterm delivery and SGA, and decreased risks of LGA and macrosomia, compared with maternal adequate GWG. Women with both prepregnancy obesity and excessive GWG had 2.2–5.9 folds higher risks of GDM, pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia compared with women with normal prepregnancy BMI and adequate GWG. Conclusions Maternal prepregnancy obesity and excessive GWG were associated with greater risks of pregnancy-induced hypertension, caesarean delivery, and greater infant size at birth. Health care providers should inform women to start the pregnancy with a BMI in the normal weight category and limit their GWG to the range specified for their prepregnancy BMI. PMID:24376527

Estrogen or raloxifene during postmenopausal weight loss: adiposity and cardiometabolic outcomes.

PubMed

Van Pelt, R E; Gozansky, W S; Wolfe, P; Kittelson, J M; Jankowski, C M; Schwartz, R S; Kohrt, W M

2014-04-01

Estrogen-based hormone therapy (HT) attenuates abdominal fat gain after menopause, but whether HT improves abdominal fat loss during weight loss is unknown. It was hypothesized that HT or a selective estrogen receptor modulator (raloxifene) would augment reductions in abdominal visceral fat during weight loss when compared to placebo, potentially increasing improvements in glucose tolerance and lipid profile. Healthy postmenopausal women (n = 119; age 50-70 yr) underwent a 6-month weight-loss (primarily exercise) intervention with randomization to raloxifene (60 mg/d), HT (conjugated estrogens, 0.625 mg/d), or placebo. Outcomes were change in total and abdominal (visceral and subcutaneous) fat mass, lipid profile, and fasting and post-challenge glucose and insulin. Neither HT nor raloxifene augmented loss of total or abdominal fat mass during exercise-induced weight loss when compared with placebo. Weight loss-induced improvements in risk factors were similar among the three groups, except for a greater reduction in fasted glucose in the HT group (difference in change [95%CI] from placebo; -0.40 [-0.76, -0.05]) and greater reductions in LDL (-0.36 [-0.63, -0.09]) and increases in HDL (0.15 [0.07, 0.24]) in both treatment groups. Postmenopausal HT and raloxifene did not increase abdominal fat loss during weight loss, but did improve some cardiometabolic outcomes. Copyright © 2013 The Obesity Society.

Does bone loss begin after weight loss ends? Results 2 years after weight loss or regain in postmenopausal women.

PubMed

Von Thun, Nancy L; Sukumar, Deeptha; Heymsfield, Steven B; Shapses, Sue A

2014-05-01

Short-term weight loss is accompanied by bone loss in postmenopausal women. The longer-term impact of weight loss on bone in reduced overweight/obese women compared with women who regained their weight was examined in this study using a case-control design. Postmenopausal women (N = 42; mean [SD] body mass index, 28.3 [2.8] kg/m; mean [SD] age, 60.7 [5.5] y) were recruited 2 years after the start of a 6-month weight loss trial; those who maintained their weight (weight loss maintainer [WL-M] group) were matched to a cohort of women who regained their weight (weight loss regainer [WL-R] group). Serum hormones and bone markers were measured in a subset. Bone mineral density (BMD) at the femoral neck, trochanter, spine, radius, and total body, and soft-tissue composition were taken at baseline, 0.5 years, and 2 years. During weight loss, both groups lost 9.3% (3.4%) of body weight, with no significant difference between the groups. After weight loss, weight change was -0.1% (2.7%) and 6.0% (3.3%) in the WL-M (n = 22) and WL-R (n = 20) groups, respectively. After 2 years, both groups lost BMD at the femoral neck and trochanter (P ≤ 0.01), whereas only the WL-M group reduced BMD at the 1/3 radius (P < 0.001). There was greater BMD loss at the trochanter (-6.8% [5.7%]) and 1/3 radius (-4.5% [3.3%]) in the WL-M group compared with the WL-R group after 2 years. Multiple linear regression showed that change in leg fat mass (but not trunk fat) contributed to trochanter BMD loss (P < 0.05). After 2 years, there is no BMD recovery of weight reduction-induced bone loss, irrespective of weight regain. These data suggest that the period after weight loss may be an important point in time to prevent bone loss for those who maintain weight and those who regain weight.

Do Lactation-Induced Changes in Ghrelin, Glucagon-Like Peptide-1, and Peptide YY Influence Appetite and Body Weight Regulation during the First Postpartum Year?

PubMed Central

Larson-Meyer, D. Enette; Schueler, Jessica; Kyle, Erin; Austin, Kathleen J.; Hart, Ann Marie; Alexander, Brenda M.

2016-01-01

To determine whether fasting and meal-induced appetite-regulating hormones are altered during lactation and associated with body weight retention after childbearing, we studied 24 exclusively breastfeeding women (BMI = 25.2 ± 3.6 kg/m2) at 4-5 weeks postpartum and 20 never-pregnant controls (BMI = 24.0 ± 3.1 kg/m2). Ghrelin, PYY, GLP-1, and appetite ratings were measured before/and 150 minutes after a standardized breakfast and 60 minutes after an ad libitum lunch. Body weight/composition were measured at 6 and 12 months. Fasting and area under-the-curve responses for appetite-regulating hormones did not differ between lactating and control groups; ghrelinacyl, however, tended to track higher after the standardized breakfast in lactating women and was higher (p < 0.05) after the ad libitum lunch despite a 24% higher energy intake (p < 0.05). By 12 months, lactating women lost 5.3 ± 2.2 kg (n = 18), whereas control women (n = 15) remained weight stable (p = 0.019); fifteen of the lactating women returned to within ±2.0 kg of prepregnancy weight but three retained >6.0 kg. The retainers had greater (p < 0.05) postmeal ghrelin rebound responses following breakfast. Overall these studies do not support the hypothesis that appetite-regulating hormones are altered during lactation and associated with postpartum weight retention. Altered ghrelin responses, however, deserve further exploration. PMID:27313876

Hormonal Correlates of Clozapine-Induced Weight Gain in Psychotic Children: An Exploratory Study

ERIC Educational Resources Information Center

Sporn, Alexandra L.; Bobb, Aaron J.; Gogtay, Nitin; Stevens, Hanna; Greenstein, Deanna K.; Clasen, Liv S.; Tossell, Julia W.; Nugent, Thomas; Gochman, Peter A.; Sharp, Wendy S.; Mattai, Anand; Lenane, Marge C.; Yanovski, Jack A.; Rapoport, Judith L.

2005-01-01

Objective: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Method: Fasting serum samples for 24 patients with COS and 21 matched healthy controls…

Egg breakfast enhances weight loss

PubMed Central

Vander Wal, JS; Gupta, A; Khosla, P; Dhurandhar, NV

2009-01-01

Objective To test the hypotheses that an egg breakfast, in contrast to a bagel breakfast matched for energy density and total energy, would enhance weight loss in overweight and obese participants while on a reduced-calorie weight loss diet. Subjects Men and women (n=152), age 25–60 years, body mass index (BMI) ≥25 and ≤50 kg m−2. Design Otherwise healthy overweight or obese participants were assigned to Egg (E), Egg Diet (ED), Bagel (B) or Bagel Diet (BD) groups, based on the prescription of either an egg breakfast containing two eggs (340 kcal) or a breakfast containing bagels matched for energy density and total energy, for at least 5 days per week, respectively. The ED and BD groups were suggested a 1000 kcal energy-deficit low-fat diet, whereas the B and E groups were asked not to change their energy intake. Results After 8 weeks, in comparison to the BD group, the ED group showed a 61% greater reduction in BMI (−0.95±0.82 vs −0.59±0.85, P<0.05), a 65% greater weight loss (−2.63±2.33 vs −1.59±2.38 kg, P<0.05), a 34% greater reduction in waist circumference (P<0.06) and a 16% greater reduction in percent body fat (P=not significant). No significant differences between the E and B groups on the aforementioned variables were obtained. Further, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, did not differ between the groups. Conclusions The egg breakfast enhances weight loss, when combined with an energy-deficit diet, but does not induce weight loss in a free-living condition. The inclusion of eggs in a weight management program may offer a nutritious supplement to enhance weight loss. PMID:18679412

Perceived weight discrimination and changes in weight, waist circumference, and weight status.

PubMed

Jackson, Sarah E; Beeken, Rebecca J; Wardle, Jane

2014-12-01

To examine associations between perceived weight discrimination and changes in weight, waist circumference, and weight status. Data were from 2944 men and women aged ≥50 years participating in the English Longitudinal Study of Ageing. Experiences of weight discrimination were reported in 2010-2011 and weight and waist circumference were objectively measured in 2008-2009 and 2012-2013. ANCOVAs were used to test associations between perceived weight discrimination and changes in weight and waist circumference. Logistic regression was used to test associations with changes in weight status. All analyses adjusted for baseline BMI, age, sex, and wealth. Perceived weight discrimination was associated with relative increases in weight (+1.66 kg, P < 0.001) and waist circumference (+1.12 cm, P = 0.046). There was also a significant association with odds of becoming obese over the follow-up period (OR = 6.67, 95% CI 1.85-24.04) but odds of remaining obese did not differ according to experiences of weight discrimination (OR = 1.09, 95% CI 0.46-2.59). Our results indicate that rather than encouraging people to lose weight, weight discrimination promotes weight gain and the onset of obesity. Implementing effective interventions to combat weight stigma and discrimination at the population level could reduce the burden of obesity. © 2014 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Use of dynamic weight bearing as a novel end-point for the assessment of abdominal pain in the LPS-induced peritonitis model in the rat.

PubMed

Gruen, Michael; Laux-Biehlmann, Alexis; Zollner, Thomas M; Nagel, Jens

2014-07-30

Chronic pelvic pain (CPP) is defined as long-lasting and severe pelvic pain persisting over six months in cyclic or non-cyclic chronic manner. Various pathologic conditions like endometriosis, abdominal infections, intra-peritoneal adhesions or infection, underlie CPP which is often the leading symptom of the associated diseases. Pharmacological approaches addressing CPP are hampered by the absence of a straight-forward, objective, and reliable method for the assessment of CPP in rodents. In the presented study, the dynamic weight bearing system (DWB) was employed for the first time for the evaluation of pelvic pain in a rat model of LPS-induced peritonitis. Rats were pretreated with the COX-2 inhibitor rofecoxib and PGE2 levels were evaluated in peritoneal lavage. DWB analysis revealed that rats treated with LPS showed a relief posture by a significantly increased weight distribution to the front when compared to vehicle-treated animals. This effect was prevented by rofecoxib treatment indicating the sensitivity of the model for pelvic pain related to peritonitis. Analysis of the PGE2 levels in the peritoneal fluid indicated a correlation with the relief posture intensity. In contrast to others weight bearing approaches, the use of DWB allows evaluation of spontaneous posture changes as a consequence of pelvic pain. Taken together, we were able to show, that DWB combined with LPS-induced peritonitis may deliver a new reliable animal model addressing pelvic pain with high construct validity (peritoneal inflammation), and face validity (pain related relief posture). Copyright © 2014 Elsevier B.V. All rights reserved.