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4261 Insulin Sensitizing Effects of Vitamin D Mediated through Reduced Adipose Tissue Inflammation and Fibrosis: Evidence from a Human Randomized Trial and Mice Studies
- Eric Lontchi Yimagou, Sona Kang, Kehao Zhang, Akankasha Goyal, Jee Young You, Evan Rosen, Preeti Kishore, Meredith Hawkins
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 97-98
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OBJECTIVES/GOALS: Vitamin D [25(OH)D], known to have anti-inflammatory and anti-fibrotic effects in other tissues, may also impact adipose tissue. We designed parallel studies in humans and rodents to define the effects of vitamin D on adipose tissue inflammation and fibrosis, and on systemic insulin resistance. METHODS/STUDY POPULATION: We performed a randomized, double-blinded placebo-controlled trial to examine the effects of repleting vitamin D at to two levels (to >30 ng/ml and to > 50 ng/ml) in 25(OH)D-deficient (<20 ng/ml), insulin resistant, overweight-to-obese humans (n = 19). A comprehensive study of whole-body insulin action was undertaken with euglycemic stepped hyperinsulinemic clamp studies, both before (1st visit) and after administration of vitamin D or placebo (2nd visit and 3rd visit). Adipose tissue fibrosis and inflammation were quantified by ‘real-time’ rt-PCR and immunofluorescence. To determine whether vitamin D’s effects are mediated through adipocytes, we performed hyperinsulinemic clamp studies and adipose tissue analysis in an adipocyte-specific vitamin D receptor knockout (VDR KO) mouse model. RESULTS/ANTICIPATED RESULTS: 25(OH)D repletion (to >30 ng/ml) was associated with reductions in adipose tissue expression of inflammatory (0.6-0.7-fold decreased expression of TNF-α, IL-6, iNOS and PAI-1) and pro-fibrotic (0.4-0.8-fold decreased expression of TGF-β1, HiF1α, Collagen I, V, VI and MMP7) factors, decreased collagen VI immunofluorescence (p = 0.02) and improved hepatic insulin sensitivity in humans, with suppression of endogenous glucose production (EGP) (1.28 ± 0.20 vs 0.88 ± 0.18 mg/kg/min, p = 0.03). Compared to wild type (WT), VDR KO mice exhibited increased adipose tissue expression of several pro-inflammatory (Tnf-α, iNos, Pai-1, Mcp-1 and F4/80; 4-10 fold) and pro-fibrotic genes (Tgf-β1, Collagen VI, and Tsp1; 2-4 fold), in concert with hepatic insulin resistance (EGP 10 ± 3 vs 3 ± 2 mg/kg/min in WT, p = 0.021). DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these complementary human and rodent studies establish a beneficial role of vitamin D to improve hepatic insulin resistance, likely by restraining adipose tissue inflammation and fibrosis. Thus, normalizing 25(OH)D levels could have metabolic benefits in targeted individuals. CONFLICT OF INTEREST DESCRIPTION: N/A
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- By Brittany L. Anderson-Montoya, Heather R. Bailey, Carryl L. Baldwin, Daphne Bavelier, Jameson D. Beach, Jeffrey S. Bedwell, Kevin B. Bennett, Richard A. Block, Deborah A. Boehm-Davis, Corey J. Bohil, David B. Boles, Avinoam Borowsky, Jessica Bramlett, Allison A. Brennan, J. Christopher Brill, Matthew S. Cain, Meredith Carroll, Roberto Champney, Kait Clark, Nancy J. Cooke, Lori M. Curtindale, Clare Davies, Patricia R. DeLucia, Andrew E. Deptula, Michael B. Dillard, Colin D. Drury, Christopher Edman, James T. Enns, Sara Irina Fabrikant, Victor S. Finomore, Arthur D. Fisk, John M. Flach, Matthew E. Funke, Andre Garcia, Adam Gazzaley, Douglas J. Gillan, Rebecca A. Grier, Simen Hagen, Kelly Hale, Diane F. Halpern, Peter A. Hancock, Deborah L. Harm, Mary Hegarty, Laurie M. Heller, Nicole D. Helton, William S. Helton, Robert R. Hoffman, Jerred Holt, Xiaogang Hu, Richard J. Jagacinski, Keith S. Jones, Astrid M. L. Kappers, Simon Kemp, Robert C. Kennedy, Robert S. Kennedy, Alan Kingstone, Ioana Koglbauer, Norman E. Lane, Robert D. Latzman, Cynthia Laurie-Rose, Patricia Lee, Richard Lowe, Valerie Lugo, Poornima Madhavan, Leonard S. Mark, Gerald Matthews, Jyoti Mishra, Stephen R. Mitroff, Tracy L. Mitzner, Alexander M. Morison, Taylor Murphy, Takamichi Nakamoto, John G. Neuhoff, Karl M. Newell, Tal Oron-Gilad, Raja Parasuraman, Tiffany A. Pempek, Robert W. Proctor, Katie A. Ragsdale, Anil K. Raj, Millard F. Reschke, Evan F. Risko, Matthew Rizzo, Wendy A. Rogers, Jesse Q. Sargent, Mark W. Scerbo, Natasha B. Schwartz, F. Jacob Seagull, Cory-Ann Smarr, L. James Smart, Kay Stanney, James Staszewski, Clayton L. Stephenson, Mary E. Stuart, Breanna E. Studenka, Joel Suss, Leedjia Svec, James L. Szalma, James Tanaka, James Thompson, Wouter M. Bergmann Tiest, Lauren A. Vassiliades, Michael A. Vidulich, Paul Ward, Joel S. Warm, David A. Washburn, Christopher D. Wickens, Scott J. Wood, David D. Woods, Motonori Yamaguchi, Lin Ye, Jeffrey M. Zacks
- Edited by Robert R. Hoffman, Peter A. Hancock, University of Central Florida, Mark W. Scerbo, Old Dominion University, Virginia, Raja Parasuraman, George Mason University, Virginia, James L. Szalma, University of Central Florida
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- Book:
- The Cambridge Handbook of Applied Perception Research
- Published online:
- 05 July 2015
- Print publication:
- 26 January 2015, pp xi-xiv
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Familial influences on internalizing symptomatology in Latino adolescents: An ecological analysis of parent mental health and acculturation dynamics
- Paul R. Smokowski, Roderick A. Rose, Caroline B. R. Evans, Katie L. Cotter, Meredith Bower, Martica Bacallao
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- Journal:
- Development and Psychopathology / Volume 26 / Issue 4pt2 / November 2014
- Published online by Cambridge University Press:
- 25 November 2014, pp. 1191-1207
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The aim of this study was to examine if family system dynamics (e.g., parent mental health, marriage quality, conflict, and cohesion) that have often been overlooked when studying Latino families play a more important role in predicting adolescent internalizing symptoms than acculturation processes. Data comes from the Latino Acculturation and Health Project, a longitudinal investigation of acculturation in Latino families in North Carolina and Arizona (Smokowski & Bacallao, 2006, 2010). Researchers conducted in-depth, community-based interviews with 258 Latino adolescents and 258 of their parents in metropolitan, small-town, and rural areas. Interviews were conducted at four time points at intervals of approximately 6 months. Parent and adolescent ratings of the adolescent's internalizing symptoms were used as the dependent variable in a longitudinal hierarchical linear model with a rater effects structure. Results showed that parent–adolescent conflict and parent mental health (fear/avoidance of social situations and humiliation sensitivity) were significant predictors of adolescent internalizing symptoms. Acculturation scales were not significant predictors; however, internalizing symptoms decreased with time spent in the United States. Females and adolescents from lower socioeconomic status families reported more internalizing symptoms, while participants who had been in the United States longer reported fewer internalizing symptoms. Implications were discussed.
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- By Tod C. Aeby, Melanie D. Altizer, Ronan A. Bakker, Meghann E. Batten, Anita K. Blanchard, Brian Bond, Megan A. Brady, Saweda A. Bright, Ellen L. Brock, Amy Brown, Ashley Carroll, Jori S. Carter, Frances Casey, Weldon Chafe, David Chelmow, Jessica M. Ciaburri, Stephen A. Cohen, Adrianne M. Colton, PonJola Coney, Jennifer A. Cross, Julie Zemaitis DeCesare, Layson L. Denney, Megan L. Evans, Nicole S. Fanning, Tanaz R. Ferzandi, Katie P. Friday, Nancy D. Gaba, Rajiv B. Gala, Andrew Galffy, Adrienne L. Gentry, Edward J. Gill, Philippe Girerd, Meredith Gray, Amy Hempel, Audra Jolyn Hill, Chris J. Hong, Kathryn A. Houston, Patricia S. Huguelet, Warner K. Huh, Jordan Hylton, Christine R. Isaacs, Alison F. Jacoby, Isaiah M. Johnson, Nicole W. Karjane, Emily E. Landers, Susan M. Lanni, Eduardo Lara-Torre, Lee A. Learman, Nikola Alexander Letham, Rachel K. Love, Richard Scott Lucidi, Elisabeth McGaw, Kimberly Woods McMorrow, Christopher A. Manipula, Kirk J. Matthews, Michelle Meglin, Megan Metcalf, Sarah H. Milton, Gaby Moawad, Christopher Morosky, Lindsay H. Morrell, Elizabeth L. Munter, Erin L. Murata, Amanda B. Murchison, Nguyet A. Nguyen, Nan G. O’Connell, Tony Ogburn, K. Nathan Parthasarathy, Thomas C. Peng, Ashley Peterson, Sarah Peterson, John G. Pierce, Amber Price, Heidi J. Purcell, Ronald M. Ramus, Nicole Calloway Rankins, Fidelma B. Rigby, Amanda H. Ritter, Barbara L. Robinson, Danielle Roncari, Lisa Rubinsak, Jennifer Salcedo, Mary T. Sale, Peter F. Schnatz, John W. Seeds, Kathryn Shaia, Karen Shelton, Megan M. Shine, Haller J. Smith, Roger P. Smith, Nancy A. Sokkary, Reni A. Soon, Aparna Sridhar, Lilja Stefansson, Laurie S. Swaim, Chemen M. Tate, Hong-Thao Thieu, Meredith S. Thomas, L. Chesney Thompson, Tiffany Tonismae, Angela M. Tran, Breanna Walker, Alan G. Waxman, C. Nathan Webb, Valerie L. Williams, Sarah B. Wilson, Elizabeth M. Yoselevsky, Amy E. Young
- Edited by David Chelmow, Virginia Commonwealth University, Christine R. Isaacs, Virginia Commonwealth University, Ashley Carroll, Virginia Commonwealth University
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- Book:
- Acute Care and Emergency Gynecology
- Published online:
- 05 November 2014
- Print publication:
- 30 October 2014, pp ix-xiv
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Effect of increasing voluntary folic acid food fortification on dietary folate intakes and adequacy of reproductive-age women in New Zealand
- Sophie E Evans, Vanessa L Mygind, Meredith C Peddie, Jody C Miller, Lisa A Houghton
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- Journal:
- Public Health Nutrition / Volume 17 / Issue 7 / July 2014
- Published online by Cambridge University Press:
- 09 July 2013, pp. 1447-1453
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Objective
Mandatory folic acid fortification of breads in New Zealand was put on hold in 2009. At this time, bread manufacturers were requested to adopt greater voluntary fortification and agreed to add folic acid to approximately one-third of their bread range. We sought to evaluate the impact of increased voluntary fortification of bread and the proposed mandatory fortification programme on folate intake adequacy of reproductive-age women.
DesignCross-sectional study conducted in 2008. Dietary data were collected using 3 d weighed food records and usual folate intakes were generated by modifying the food composition table as follows: (i) voluntary fortification of bread as of 2008 (six breads); (ii) increased voluntary fortification of bread as of 2011 (thirty-four breads); and (iii) mandatory fortification of all breads. The prevalence of inadequate folate intake was calculated for all three scenarios using the Estimated Average Requirement (320 μg dietary folate equivalents/d) cut-point method.
SettingNew Zealand.
SubjectsHealthy non-pregnant women (n 125) aged 18–40 years.
ResultsUsual folate intake in 2008 was 362 μg dietary folate equivalents/d. Increased voluntary bread fortification led to a marginal increase in folate intakes (394 μg dietary folate equivalents/d) and a decline in inadequacy from 37 % to 29 %. Mandatory fortification resulted in an increase of 89 μg folic acid/d, which substantially shifted both the proportion of women with folic acid intakes above 100 μg/d and the distribution of overall folate intakes, producing a marked reduction in inadequacy to 5 %.
ConclusionsIncreased voluntary bread fortification efforts are far inferior to mandatory fortification as a reliable public health intervention.
Contributors
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- By Aakash Agarwala, Linda S. Aglio, Rae M. Allain, Paul D. Allen, Houman Amirfarzan, Yasodananda Kumar Areti, Amit Asopa, Edwin G. Avery, Patricia R. Bachiller, Angela M. Bader, Rana Badr, Sibinka Bajic, David J. Baker, Sheila R. Barnett, Rena Beckerly, Lorenzo Berra, Walter Bethune, Sascha S. Beutler, Tarun Bhalla, Edward A. Bittner, Jonathan D. Bloom, Alina V. Bodas, Lina M. Bolanos-Diaz, Ruma R. Bose, Jan Boublik, John P. Broadnax, Jason C. Brookman, Meredith R. Brooks, Roland Brusseau, Ethan O. Bryson, Linda A. Bulich, Kenji Butterfield, William R. Camann, Denise M. Chan, Theresa S. Chang, Jonathan E. Charnin, Mark Chrostowski, Fred Cobey, Adam B. Collins, Mercedes A. Concepcion, Christopher W. Connor, Bronwyn Cooper, Jeffrey B. Cooper, Martha Cordoba-Amorocho, Stephen B. Corn, Darin J. Correll, Gregory J. Crosby, Lisa J. Crossley, Deborah J. Culley, Tomas Cvrk, Michael N. D'Ambra, Michael Decker, Daniel F. Dedrick, Mark Dershwitz, Francis X. Dillon, Pradeep Dinakar, Alimorad G. Djalali, D. John Doyle, Lambertus Drop, Ian F. Dunn, Theodore E. Dushane, Sunil Eappen, Thomas Edrich, Jesse M. Ehrenfeld, Jason M. Erlich, Lucinda L. Everett, Elliott S. Farber, Khaldoun Faris, Eddy M. Feliz, Massimo Ferrigno, Richard S. Field, Michael G. Fitzsimons, Hugh L. Flanagan Jr., Vladimir Formanek, Amanda A. Fox, John A. Fox, Gyorgy Frendl, Tanja S. Frey, Samuel M. Galvagno Jr., Edward R. Garcia, Jonathan D. Gates, Cosmin Gauran, Brian J. Gelfand, Simon Gelman, Alexander C. Gerhart, Peter Gerner, Omid Ghalambor, Christopher J. Gilligan, Christian D. Gonzalez, Noah E. Gordon, William B. Gormley, Thomas J. Graetz, Wendy L. Gross, Amit Gupta, James P. Hardy, Seetharaman Hariharan, Miriam Harnett, Philip M. Hartigan, Joaquim M. Havens, Bishr Haydar, Stephen O. Heard, James L. Helstrom, David L. Hepner, McCallum R. Hoyt, Robert N. Jamison, Karinne Jervis, Stephanie B. Jones, Swaminathan Karthik, Richard M. Kaufman, Shubjeet Kaur, Lee A. Kearse Jr., John C. Keel, Scott D. Kelley, Albert H. Kim, Amy L. Kim, Grace Y. Kim, Robert J. Klickovich, Robert M. Knapp, Bhavani S. Kodali, Rahul Koka, Alina Lazar, Laura H. Leduc, Stanley Leeson, Lisa R. Leffert, Scott A. LeGrand, Patricio Leyton, J. Lance Lichtor, John Lin, Alvaro A. Macias, Karan Madan, Sohail K. Mahboobi, Devi Mahendran, Christine Mai, Sayeed Malek, S. Rao Mallampati, Thomas J. Mancuso, Ramon Martin, Matthew C. Martinez, J. A. Jeevendra Martyn, Kai Matthes, Tommaso Mauri, Mary Ellen McCann, Shannon S. McKenna, Dennis J. McNicholl, Abdel-Kader Mehio, Thor C. Milland, Tonya L. K. Miller, John D. Mitchell, K. Annette Mizuguchi, Naila Moghul, David R. Moss, Ross J. Musumeci, Naveen Nathan, Ju-Mei Ng, Liem C. Nguyen, Ervant Nishanian, Martina Nowak, Ala Nozari, Michael Nurok, Arti Ori, Rafael A. Ortega, Amy J. Ortman, David Oxman, Arvind Palanisamy, Carlo Pancaro, Lisbeth Lopez Pappas, Benjamin Parish, Samuel Park, Deborah S. Pederson, Beverly K. Philip, James H. Philip, Silvia Pivi, Stephen D. Pratt, Douglas E. Raines, Stephen L. Ratcliff, James P. Rathmell, J. Taylor Reed, Elizabeth M. Rickerson, Selwyn O. Rogers Jr., Thomas M. Romanelli, William H. Rosenblatt, Carl E. Rosow, Edgar L. Ross, J. Victor Ryckman, Mônica M. Sá Rêgo, Nicholas Sadovnikoff, Warren S. Sandberg, Annette Y. Schure, B. Scott Segal, Navil F. Sethna, Swapneel K. Shah, Shaheen F. Shaikh, Fred E. Shapiro, Torin D. Shear, Prem S. Shekar, Stanton K. Shernan, Naomi Shimizu, Douglas C. Shook, Kamal K. Sikka, Pankaj K. Sikka, David A. Silver, Jeffrey H. Silverstein, Emily A. Singer, Ken Solt, Spiro G. Spanakis, Wolfgang Steudel, Matthias Stopfkuchen-Evans, Michael P. Storey, Gary R. Strichartz, Balachundhar Subramaniam, Wariya Sukhupragarn, John Summers, Shine Sun, Eswar Sundar, Sugantha Sundar, Neelakantan Sunder, Faraz Syed, Usha B. Tedrow, Nelson L. Thaemert, George P. Topulos, Lawrence C. Tsen, Richard D. Urman, Charles A. Vacanti, Francis X. Vacanti, Joshua C. Vacanti, Assia Valovska, Ivan T. Valovski, Mary Ann Vann, Susan Vassallo, Anasuya Vasudevan, Kamen V. Vlassakov, Gian Paolo Volpato, Essi M. Vulli, J. Matthias Walz, Jingping Wang, James F. Watkins, Maxwell Weinmann, Sharon L. Wetherall, Mallory Williams, Sarah H. Wiser, Zhiling Xiong, Warren M. Zapol, Jie Zhou
- Edited by Charles Vacanti, Scott Segal, Pankaj Sikka, Richard Urman
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- Book:
- Essential Clinical Anesthesia
- Published online:
- 05 January 2012
- Print publication:
- 11 July 2011, pp xv-xxviii
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The impact of oral health on the quality of life of young patients with congenital cardiac disease
- Marcio A. da Fonseca, Meredith Evans, Douglas Teske, Sarat Thikkurissy, Homa Amini
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- Journal:
- Cardiology in the Young / Volume 19 / Issue 3 / June 2009
- Published online by Cambridge University Press:
- 14 April 2009, pp. 252-256
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The purposes of our study were, first, to determine the prevalence of dental caries in young patients with congenital cardiac disease, second, to determine the effect of oral health in their quality of life, third, to examine parental knowledge about associations between oral health and cardiac health, and fourth, to examine parental perceptions regarding access to dental care. A standardized questionnaire was given to a convenience sample of parents of 43 children with cardiac disease and 43 healthy controls from 12 to 71 months of age. In every patient, we performed a dental examination. Descriptive statistics, the two-tailed t-test, and Fisher’s exact test were used for statistical analysis. Of the children with cardiac disease, 17% had caries, compared to 13% of the control group. Almost half of those with cardiac disease had never seen a dentist, compared to 35% of the control subjects. Of the parents of those with cardiac disease, one-fifth did not know whether oral health was important for the heart, compared to one-tenth of controls. Insurance and access to care were not barriers to obtain dental treatment. Statistically significant differences were, first, parents of children with congenitally malformed hearts felt more guilt about their child’s oral health than control parents (p = 0.026), second, they were more upset about the dental problems and/or treatments of their children (p = 0.012), and third, they thought that dental problems and/or dental treatment made their children more irritable (p = 0.012). Our findings indicate that it is of paramount importance that cardiologists and their associated staff educate patients and families about oral health and other issues associated with congenital cardiac disease.
Long-Term Characterization of 6H-SiC Transistor Integrated Circuit Technology Operating at 500 °C
- Philip Neudeck, David J. Spry, Liang-Yu Chen, Carl W. Chang, Glenn M. Beheim, Robert S. Okojie, Laura J. Evans, Roger D. Meredith, Terry L. Ferrier, Michael J. Krasowski, Norman F. Prokop
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- Journal:
- MRS Online Proceedings Library Archive / Volume 1069 / 2008
- Published online by Cambridge University Press:
- 01 February 2011, 1069-D11-02
- Print publication:
- 2008
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NASA has been developing very high temperature semiconductor integrated circuits for use in the hot sections of aircraft engines and for Venus exploration. This paper reports on long-term 500 °C electrical operation of prototype 6H-SiC integrated circuits based on epitaxial 6H-SiC junction field effect transistors (JFETs). As of this writing, some devices have surpassed 4000 hours of continuous 500 °C electrical operation in oxidizing air atmosphere with minimal change in relevant electrical parameters.