Search

Your search keyword '"Lu Huogen"' showing total 10 results
Start Over Author "Lu Huogen" Search Limiters Full Text
10 results on '"Lu Huogen"'

4. Lecithin Cholesterol Acyltransferase Null Mice Are Protected from Diet-induced Obesity and Insulin Resistance in a Gender-specific Manner through Multiple Pathways

Author

Mohammad A. Hossain, Dominic S. Ng, Stephanie A. Schroer, Lixin Li, Philip W. Connelly, Minna Woo, Lu Liu, Sabreena Sadat, Lu Huogen, Lauren Hager, Laetitia Tam, and I. George Fantus

Subjects
Male, Sucrose, medicine.medical_specialty, Adipose Tissue, White, Adipose tissue, White adipose tissue, AMP-Activated Protein Kinases, Biology, Biochemistry, Ion Channels, Mitochondrial Proteins, Phosphatidylcholine-Sterol O-Acyltransferase, Mice, Insulin resistance, Lecithin Cholesterol Acyltransferase Deficiency, Internal medicine, Brown adipose tissue, medicine, Animals, Uncoupling Protein 3, Obesity, Muscle, Skeletal, Endoplasmic Reticulum Chaperone BiP, Molecular Biology, Heat-Shock Proteins, Uncoupling Protein 1, Mice, Knockout, Sex Characteristics, Lecithin cholesterol acyltransferase deficiency, Cell Biology, medicine.disease, Dietary Fats, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Thermogenin, Diet, Wnt Proteins, Metabolism, medicine.anatomical_structure, Endocrinology, Receptors, LDL, Adipogenesis, Sweetening Agents, LDL receptor, Trans-Activators, Unfolded Protein Response, Female, Insulin Resistance, Transcription Factor CHOP, Transcription Factors
Abstract

Complete lecithin cholesterol acyltransferase (LCAT) deficiency uniformly results in a profound HDL deficiency. We recently reported unexpected enhanced insulin sensitivity in LCAT knock-out mice in the LDL receptor knock-out background (Ldlr(-/-)×Lcat(-/-); double knock-out (DKO)), when compared with their Ldlr(-/-)×Lcat(+/+) (single knock-out (SKO)) controls. Here, we report that LCAT-deficient mice (DKO and Lcat(-/-)) are protected against high fat high sucrose (HFHS) diet-induced obesity without hypophagia in a gender-specific manner compared with their respective (SKO and WT) controls. The metabolic phenotypes are more pronounced in the females. Changes in endoplasmic reticulum stress were examined as a possible mechanism for the metabolic protection. The female DKO mice developed attenuated HFHS-induced endoplasmic reticulum stress as evidenced by a lack of increase in mRNA levels of the hepatic unfolded protein response (UPR) markers Grp78 and CHOP compared with SKO controls. The DKO female mice were also protected against diet-induced insulin resistance. In white adipose tissue of chow-fed DKO mice, we also observed a reduction in UPR, gene markers for adipogenesis, and markers for activation of Wnt signaling. In skeletal muscles of female DKO mice, we observed an unexpected increase in UCP1 in association with increase in phospho-AMPKα, PGC1α, and UCP3 expressions. This increase in UCP1 was associated with ectopic islands of brown adipocytes between skeletal muscle fibers. Our findings suggest that LCAT deficiency confers gender-specific protection against diet-induced obesity and insulin resistance at least in part through regulation in UPR, white adipose tissue adipogenesis, and brown adipocyte partitioning.

Published
2011
Full Text
View/download PDF

5. Combined Hyperglycemia- and Hyperinsulinemia-Induced Insulin Resistance in Adipocytes Is Associated With Dual Signaling Defects Mediated by PKC-ζ

Author

Lu, Huogen, primary, Bogdanovic, Elena, additional, Yu, Zhiwen, additional, Cho, Charles, additional, Liu, Lijiang, additional, Ho, Karen, additional, Guo, June, additional, Yeung, Lucy S N, additional, Lehmann, Reiner, additional, Hundal, Harinder S, additional, Giacca, Adria, additional, and Fantus, I George, additional

Published
2018
Full Text
View/download PDF

7. The Adaptor Protein p66Shc Inhibits mTOR-Dependent Anabolic Metabolism

Author

Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research at MIT, Lamming, Dudley W., Sabatini, David M., Soliman, Mohamed A., Abdel Rahman, Anas M., Birsoy, Kivanc, Pawling, Judy, Frigolet, Maria E., Lu, Huogen, Fantus, I. George, Pasculescu, Adrian, Zheng, Yong, Dennis, James W., Pawson, Tony, Sabatini, David, Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research at MIT, Lamming, Dudley W., Sabatini, David M., Soliman, Mohamed A., Abdel Rahman, Anas M., Birsoy, Kivanc, Pawling, Judy, Frigolet, Maria E., Lu, Huogen, Fantus, I. George, Pasculescu, Adrian, Zheng, Yong, Dennis, James W., Pawson, Tony, and Sabatini, David

Abstract

Adaptor proteins link surface receptors to intracellular signaling pathways and potentially control the way cells respond to nutrient availability. Mice deficient in p66Shc, the most recently evolved isoform of the Shc1 adaptor proteins and a mediator of receptor tyrosine kinase signaling, display resistance to diabetes and obesity. Using quantitative mass spectrometry, we found that p66Shc inhibited glucose metabolism. Depletion of p66Shc enhanced glycolysis and increased the allocation of glucose-derived carbon into anabolic metabolism, characteristics of a metabolic shift called the Warburg effect. This change in metabolism was mediated by the mammalian target of rapamycin (mTOR) because inhibition of mTOR with rapamycin reversed the glycolytic phenotype caused by p66Shc deficiency. Thus, unlike the other isoforms of Shc1, p66Shc appears to antagonize insulin and mTOR signaling, which limits glucose uptake and metabolism. Our results identify a critical inhibitory role for p66Shc in anabolic metabolism., National Institutes of Health (U.S.), United States. Dept. of Defense, W. M. Keck Foundation, LAM Foundation, National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award), National Institutes of Health (U.S.) (K99 Award)

Published
2015

9. The differentiation of skeletal muscle cells involves a protein-tyrosine phosphatase-alpha-mediated C-Src signaling pathway.

Author

Lu, Huogen, Shah, Poonam, Ennis, David, Shinder, Gail, Sap, Jan, Le-Tien, Hoang, Fantus, I George, Lu, Huogen, Shah, Poonam, Ennis, David, Shinder, Gail, Sap, Jan, Le-Tien, Hoang, and Fantus, I George

Abstract

Udgivelsesdato: 2002-Nov-29, Protein-tyrosine phosphatase-alpha (PTPalpha) plays an important role in various cellular signaling events, including proliferation and differentiation. In this study, we established L6 cell lines either underexpressing or overexpressing PTPalpha by stable transfection of cells with antisense PTPalpha or with full-length wild-type human or mouse or double catalytic site Cys --> Ala mutant (DM8) PTPalpha cDNA. Expression of PTPalpha in these cell lines was determined by immunoblotting and immunofluorescence. Cells harboring antisense PTPalpha exhibited a significantly reduced growth rate and thymidine incorporation when compared with the wild-type L6 cells. In contrast, cells overexpressing PTPalpha showed more rapid (2-fold) proliferation. Myoblasts with diminished PTPalpha failed to undergo fusion and did not form myotubes in reduced serum whereas overexpression of PTPalpha promoted myogenesis 2 days earlier than wild-type L6 cells. Overexpression of phosphatase-inactive mutant PTPalpha recapitulated the phenotype of the antisense cells. The different myogenic activities of these cell lines were correlated with the expression of myogenin and creatine kinase activity. Consistent with previous reports, PTPalpha positively regulated the activity of the protein-tyrosine kinase Src. Treatment of L6 cells with PP2 or SU6656, specific inhibitors of Src family kinases, and transient transfection of dominant-inhibitory Src inhibited the formation of myotubes and expression of myogenin. Moreover, enhanced expression of PTPalpha and activation of Src was detected during myogenesis. Together, these data indicate that PTPalpha is involved in the regulation of L6 myoblast growth and skeletal muscle cell differentiation via an Src-mediated signaling pathway.

Published
2002

10. The bradykinin-cGMP-PKG pathway augments insulin sensitivity via upregulation of MAPK phosphatase-5 and inhibition of JNK.

Author

Frigolet ME, Thomas G, Beard K, Lu H, Liu L, and Fantus IG

Subjects
Adipocytes metabolism, Animals, Blotting, Western, Cyclic GMP metabolism, Cyclic GMP-Dependent Protein Kinases metabolism, Dual-Specificity Phosphatases genetics, Dual-Specificity Phosphatases metabolism, Glucose metabolism, Guanylate Cyclase drug effects, Guanylate Cyclase metabolism, Immunoprecipitation, JNK Mitogen-Activated Protein Kinases drug effects, Male, Mitogen-Activated Protein Kinase Phosphatases metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type III drug effects, Nitric Oxide Synthase Type III metabolism, Phosphodiesterase Inhibitors pharmacology, Proto-Oncogene Proteins c-akt drug effects, Purinones pharmacology, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Real-Time Polymerase Chain Reaction, Signal Transduction drug effects, Adipocytes drug effects, Bradykinin pharmacology, Cyclic GMP-Dependent Protein Kinases drug effects, Dual-Specificity Phosphatases drug effects, Insulin Resistance, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinase Phosphatases drug effects, RNA, Messenger drug effects
Abstract

Bradykinin (BK) promotes insulin sensitivity and glucose uptake in adipocytes and other cell types. We demonstrated that in rat adipocytes BK enhances insulin-stimulated glucose transport via endothelial nitric oxide synthase, nitric oxide (NO) generation, and decreased activity of the mitogen-activated protein kinase (MAPK) JNK (c-Jun NH 2 -terminal kinase). In endothelial cells, NO increases soluble guanylate cyclase (sGC) activity, which, in turn, activates protein kinase G (PKG) by increasing cGMP levels. In this study, we investigated whether BK acts via the sGC-cGMP-PKG pathway to inhibit the negative effects of JNK on insulin signaling and glucose uptake in rat adipocytes. BK augmented cGMP concentrations. The BK-induced enhancement of insulin-stimulated glucose uptake was mimicked by the sGC activator YC-1 and a cell-permeable cGMP analog, CPT-cGMP, and inhibited by the sGC inhibitor ODQ and the PKG inhibitor KT 5823. Transfection of dominant-negative PKG reduced the BK augmentation of insulin-induced Akt phosphorylation. The activation of JNK and ERK1/2 by insulin was attenuated by BK, which was mediated by the sGC-cGMP-PKG pathway. Whereas insulin-stimulated phosphorylation of upstream activators of JNK and ERK, i.e., MKK4 and MEK1/2, was unaffected, BK augmented insulin-mediated induction of MKP-5 mRNA and protein levels. Furthermore, zaprinast, a phosphodiesterase inhibitor, enhanced cGMP and MKP-5 and prolonged the action of BK. These data indicate that BK enhances insulin action by inhibition of negative feedback by JNK and ERK via upregulation of MKP-5, mediated by the sGC-cGMP-PKG signaling pathway., (Copyright © 2017 the American Physiological Society.)

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results