Read by QxMD icon Read

rudolph AND leibel

Lisa Cole Burnett, Gabriela Hubner, Charles LeDuc, Michael V Morabito, Jayne F Martin Carli, Rudolph L Leibel
Global neurodevelopmental delay is a prominent characteristic of individuals with Prader-Willi syndrome (PWS). The neuromolecular bases for these delays are unknown. We identified neuroanatomical changes in the brains of mice deficient for a gene in the minimal critical deletion region for PWS (Snord116p-/m+). In Snord116p-/m+ mice, reduced primary forebrain neuron cell body size is apparent in embryonic day 15.5 fetuses, and persists until postnatal day 30 in cerebellar purkinje neurons. Snord116 is a snoRNA gene cluster of unknown function that can localize to the nucleolus...
September 6, 2017: Human Molecular Genetics
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
Beta cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ES) derived from a type 1 diabetes patient to differentiate into beta cells, and provide a source of autologous islets for cell replacement. NT-ES cells differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
September 20, 2017: Diabetes
Michael W Schwartz, Randy J Seeley, Lori M Zeltser, Adam Drewnowski, Eric Ravussin, Leanne M Redman, Rudolph L Leibel
Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight...
August 1, 2017: Endocrine Reviews
Ioanna Mosialou, Steven Shikhel, Jian-Min Liu, Antonio Maurizi, Na Luo, Zhenyan He, Yiru Huang, Haihong Zong, Richard A Friedman, Jonathan Barasch, Patricia Lanzano, Liyong Deng, Rudolph L Leibel, Mishaela Rubin, Thomas Nickolas, Wendy Chung, Lori M Zeltser, Kevin W Williams, Jeffrey E Pessin, Stavroula Kousteni
This corrects the article DOI: 10.1038/nature21697.
June 14, 2017: Nature
Ioanna Mosialou, Steven Shikhel, Jian-Min Liu, Antonio Maurizi, Na Luo, Zhenyan He, Yiru Huang, Haihong Zong, Richard A Friedman, Jonathan Barasch, Patricia Lanzano, Liyong Deng, Rudolph L Leibel, Mishaela Rubin, Thomas Nickolas, Wendy Chung, Lori M Zeltser, Kevin W Williams, Jeffrey E Pessin, Stavroula Kousteni
Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity...
March 16, 2017: Nature
Liheng Wang, Lina Sui, Sunil K Panigrahi, Kana Meece, Yurong Xin, Jinrang Kim, Jesper Gromada, Claudia A Doege, Sharon L Wardlaw, Dieter Egli, Rudolph L Leibel
We recently developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof of principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. The cognate enzyme, PC1/3, processes many prohormones in neuroendocrine and other tissues. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both short hairpin RNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons...
February 14, 2017: Stem Cell Reports
Michael V Morabito, Yann Ravussin, Bridget R Mueller, Alicja A Skowronski, Kazuhisa Watanabe, Kylie S Foo, Samuel X Lee, Anders Lehmann, Stephan Hjorth, Lori M Zeltser, Charles A LeDuc, Rudolph L Leibel
Diet-induced obesity (DIO) resulting from consumption of a high fat diet (HFD) attenuates normal neuronal responses to leptin and may contribute to the metabolic defense of an acquired higher body weight in humans; the molecular bases for the persistence of this defense are unknown. We measured the responses of 23 brain regions to exogenous leptin in 4 different groups of weight- and/or diet-perturbed mice. Responses to leptin were assessed by quantifying pSTAT3 levels in brain nuclei 30 minutes following 3 mg/kg intraperitoneal leptin...
2017: PloS One
Haiqing Hua, Linshan Shang, Hector Martinez, Matthew Freeby, Mary Pat Gallagher, Thomas Ludwig, Liyong Deng, Ellen Greenberg, Charles LeDuc, Wendy K Chung, Robin Goland, Rudolph L Leibel, Dieter Egli
No abstract text is available yet for this article.
March 1, 2017: Journal of Clinical Investigation
Ryan T Demmer, Alexander Breskin, Michael Rosenbaum, Aleksandra Zuk, Charles LeDuc, Rudolph Leibel, Bruce Paster, Moïse Desvarieux, David R Jacobs, Panos N Papapanou
BACKGROUND: Inflammation might link microbial exposures to insulin resistance. We investigated the cross-sectional association between periodontal microbiota, inflammation and insulin resistance. METHODS: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 152 diabetes-free adults (77% female) aged 20-55 years (mean = 34 ± 10). Three hundred and four subgingival plaque samples were analysed using the Human Oral Microbe Identification Microarray to measure the relative abundances of 379 taxa...
March 2017: Journal of Clinical Periodontology
Lisa C Burnett, Charles A LeDuc, Carlos R Sulsona, Daniel Paull, Richard Rausch, Sanaa Eddiry, Jayne F Martin Carli, Michael V Morabito, Alicja A Skowronski, Gabriela Hubner, Matthew Zimmer, Liheng Wang, Robert Day, Brynn Levy, Ilene Fennoy, Beatrice Dubern, Christine Poitou, Karine Clement, Merlin G Butler, Michael Rosenbaum, Jean Pierre Salles, Maithe Tauber, Daniel J Driscoll, Dieter Egli, Rudolph L Leibel
Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell-derived (iPSC-derived) neurons...
January 3, 2017: Journal of Clinical Investigation
Lisa C Burnett, Charles A LeDuc, Carlos R Sulsona, Daniel Paull, Sanaa Eddiry, Brynn Levy, Jean Pierre Salles, Maithe Tauber, Daniel J Driscoll, Dieter Egli, Rudolph L Leibel
Prader-Willi syndrome (PWS) is a syndromic obesity caused by loss of paternal gene expression in an imprinted interval on 15q11.2-q13. Induced pluripotent stem cells were generated from skin cells of three large deletion PWS patients and one unique microdeletion PWS patient. We found that genes within the PWS region, including SNRPN and NDN, showed persistence of DNA methylation after iPSC reprogramming and differentiation to neurons. Genes within the PWS minimum critical deletion region remain silenced in both PWS large deletion and microdeletion iPSC following reprogramming...
August 16, 2016: Stem Cell Research
Michael Rosenbaum, Rudolph L Leibel
OBJECTIVE: To test three proposed models for adaptive thermogenesis in compartments of energy expenditure following different degrees of weight loss. Specifically, (1) there is no adaptive thermogenesis [constant relationship of energy expenditure (EE) to metabolic mass]. (2) There is a fixed degree of adaptive thermogenesis once fat stores are below a "threshold." (3) The degree of adaptive thermogenesis is proportional to weight loss. METHODS: The relationship between weight loss and EE was examined in 17 inpatient subjects with stable weight and obesity studied at usual weight and again following a 10% and a 20% weight loss...
August 2016: Obesity
Kevin D Hall, Kong Y Chen, Juen Guo, Yan Y Lam, Rudolph L Leibel, Laurel Es Mayer, Marc L Reitman, Michael Rosenbaum, Steven R Smith, B Timothy Walsh, Eric Ravussin
BACKGROUND: The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat...
August 2016: American Journal of Clinical Nutrition
Liheng Wang, Dieter Egli, Rudolph L Leibel
The hypothalamus comprises neuronal clusters that are essential for body weight regulation and other physiological functions. Insights into the complex cellular physiology of this region of the brain are critical to understanding the pathogenesis of obesity, but human hypothalamic cells are largely inaccessible for direct study. Here we describe a technique for generation of arcuate-like hypothalamic neurons from human pluripotent stem (hPS) cells. Early activation of SHH signaling and inhibition of BMP and TGFβ signaling, followed by timed inhibition of NOTCH, can efficiently differentiate hPS cells into NKX2...
July 1, 2016: Current Protocols in Human Genetics
Kazuhisa Watanabe, Kazuhiro Nakayama, Satoshi Ohta, Kenji Tago, Supichaya Boonvisut, Elizabeth J Millings, Stuart G Fischer, Charles A LeDuc, Rudolph L Leibel, Sadahiko Iwamoto
A diabetes susceptibility gene, immunoglobulin-like domain containing receptor 2 (Ildr2), encodes a transmembrane protein localized to the endoplasmic reticulum membrane that is closely related to hepatic lipid metabolism. The livers of ob/ob mice in which Ildr2 is transiently overexpressed are relieved of hepatic steatosis. However, the molecular mechanisms through which ILDR2 affects these changes in hepatic lipid metabolism remain unknown. This study aimed to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underlying the role of ILDR2 in lipid homeostasis...
September 2, 2016: Biochemical and Biophysical Research Communications
George Stratigopoulos, Lisa Cole Burnett, Richard Rausch, Richard Gill, David Barth Penn, Alicja A Skowronski, Charles A LeDuc, Anthony J Lanzano, Pumin Zhang, Daniel R Storm, Dieter Egli, Rudolph L Leibel
Noncoding polymorphisms in the fat mass and obesity-associated (FTO) gene represent common alleles that are strongly associated with effects on food intake and adiposity in humans. Previous studies have suggested that the obesity-risk allele rs8050136 in the first intron of FTO alters a regulatory element recognized by the transcription factor CUX1, thereby leading to decreased expression of FTO and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Here, we evaluated the effects of rs8050136 and another potential CUX1 element in rs1421085 on expression of nearby genes in human induced pluripotent stem cell-derived (iPSC-derived) neurons...
May 2, 2016: Journal of Clinical Investigation
Tuomas O Kilpeläinen, Jayne F Martin Carli, Alicja A Skowronski, Qi Sun, Jennifer Kriebel, Mary F Feitosa, Åsa K Hedman, Alexander W Drong, James E Hayes, Jinghua Zhao, Tune H Pers, Ursula Schick, Niels Grarup, Zoltán Kutalik, Stella Trompet, Massimo Mangino, Kati Kristiansson, Marian Beekman, Leo-Pekka Lyytikäinen, Joel Eriksson, Peter Henneman, Jari Lahti, Toshiko Tanaka, Jian'an Luan, Fabiola Del Greco M, Dorota Pasko, Frida Renström, Sara M Willems, Anubha Mahajan, Lynda M Rose, Xiuqing Guo, Yongmei Liu, Marcus E Kleber, Louis Pérusse, Tom Gaunt, Tarunveer S Ahluwalia, Yun Ju Sung, Yolande F Ramos, Najaf Amin, Antoinette Amuzu, Inês Barroso, Claire Bellis, John Blangero, Brendan M Buckley, Stefan Böhringer, Yii-Der I Chen, Anton J N de Craen, David R Crosslin, Caroline E Dale, Zari Dastani, Felix R Day, Joris Deelen, Graciela E Delgado, Ayse Demirkan, Francis M Finucane, Ian Ford, Melissa E Garcia, Christian Gieger, Stefan Gustafsson, Göran Hallmans, Susan E Hankinson, Aki S Havulinna, Christian Herder, Dena Hernandez, Andrew A Hicks, David J Hunter, Thomas Illig, Erik Ingelsson, Andreea Ioan-Facsinay, John-Olov Jansson, Nancy S Jenny, Marit E Jørgensen, Torben Jørgensen, Magnus Karlsson, Wolfgang Koenig, Peter Kraft, Joanneke Kwekkeboom, Tiina Laatikainen, Karl-Heinz Ladwig, Charles A LeDuc, Gordon Lowe, Yingchang Lu, Pedro Marques-Vidal, Christa Meisinger, Cristina Menni, Andrew P Morris, Richard H Myers, Satu Männistö, Mike A Nalls, Lavinia Paternoster, Annette Peters, Aruna D Pradhan, Tuomo Rankinen, Laura J Rasmussen-Torvik, Wolfgang Rathmann, Treva K Rice, J Brent Richards, Paul M Ridker, Naveed Sattar, David B Savage, Stefan Söderberg, Nicholas J Timpson, Liesbeth Vandenput, Diana van Heemst, Hae-Won Uh, Marie-Claude Vohl, Mark Walker, Heinz-Erich Wichmann, Elisabeth Widén, Andrew R Wood, Jie Yao, Tanja Zeller, Yiying Zhang, Ingrid Meulenbelt, Margreet Kloppenburg, Arne Astrup, Thorkild I A Sørensen, Mark A Sarzynski, D C Rao, Pekka Jousilahti, Erkki Vartiainen, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Eero Kajantie, Clive Osmond, Aarno Palotie, Johan G Eriksson, Markku Heliövaara, Paul B Knekt, Seppo Koskinen, Antti Jula, Markus Perola, Risto K Huupponen, Jorma S Viikari, Mika Kähönen, Terho Lehtimäki, Olli T Raitakari, Dan Mellström, Mattias Lorentzon, Juan P Casas, Stefanie Bandinelli, Winfried März, Aaron Isaacs, Ko W van Dijk, Cornelia M van Duijn, Tamara B Harris, Claude Bouchard, Matthew A Allison, Daniel I Chasman, Claes Ohlsson, Lars Lind, Robert A Scott, Claudia Langenberg, Nicholas J Wareham, Luigi Ferrucci, Timothy M Frayling, Peter P Pramstaller, Ingrid B Borecki, Dawn M Waterworth, Sven Bergmann, Gérard Waeber, Peter Vollenweider, Henrik Vestergaard, Torben Hansen, Oluf Pedersen, Frank B Hu, P Eline Slagboom, Harald Grallert, Tim D Spector, J W Jukema, Robert J Klein, Erik E Schadt, Paul W Franks, Cecilia M Lindgren, Rudolph L Leibel, Ruth J F Loos
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO...
February 1, 2016: Nature Communications
Matthew J Freeby, Patricia Kringas, Robin S Goland, Rudolph L Leibel, Antonella Maffei, Chaitan Divgi, Masanori Ichise, Paul E Harris
PURPOSE: The vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing β cells and was evaluated as a biomarker of β cell mass (BCM) by positron emission tomography (PET) with [(18)F]fluoropropyl-dihydrotetrabenazine ([(18)F]FP-(+)-DTBZ). PROCEDURES: We evaluated the feasibility of longitudinal pancreatic PET VMAT2 quantification in the pancreas in two studies of healthy controls and patients with type 1 or 2 diabetes. VMAT2 binding potential (BPND) was estimated voxelwise using a reference tissue method in a cross-sectional study, followed by assessment of reproducibility using a test-retest paradigm...
April 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Michael Rosenbaum, Rob Knight, Rudolph L Leibel
Numerous studies of rodents suggest that the gut microbiota populations are sensitive to genetic and environmental influences, and can produce or influence afferent signals that directly or indirectly impinge on energy homeostatic systems affecting both energy balance (weight gain or loss) and energy stores. Fecal transplants from obese and lean human, and from mouse donors to gnotobiotic mice, result in adoption of the donor somatotype by the formerly germ-free rodents. Thus, the microbiota is certainly implicated in the development of obesity, adiposity-related comorbidities, and the response to interventions designed to achieve sustained weight reduction in mice...
September 2015: Trends in Endocrinology and Metabolism: TEM
Gabrielle Page-Wilson, Kana Meece, Anne White, Michael Rosenbaum, Rudolph L Leibel, Richard Smiley, Sharon L Wardlaw
Leptin and its neuronal targets, which produce proopiomelanocortin (POMC) and agouti-related protein (AgRP), regulate energy balance. This study characterized leptin, POMC, and AgRP in the cerebrospinal fluid (CSF) of 47 healthy human subjects, 23 lean and 24 overweight/obese (OW/OB), as related to BMI, adiposity, plasma leptin, soluble leptin receptor (s-OB-R), and insulin. POMC was measured since the POMC prohormone is the predominant POMC peptide in CSF and correlates with hypothalamic POMC in rodents. Plasma AgRP was similarly characterized...
September 1, 2015: American Journal of Physiology. Endocrinology and Metabolism
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"