Member Listing

Name

Denise Fernandez-Twinn

Affiliation

Department of Clinical Biochemistry, Metabolic Research Laboratories, MRC Metabolic Diseases Unit

Title

Dr

Role

Post Doctoral

Research Summary

Programmed changes in miRNA expression link early life nutrition to long-term health.  Specifically, my work has shown that miR-483-3p is up-regulated in adipose tissue from low birth-weight adult humans and pre-diabetic adult rats exposed to sub-optimal nutrition in early life. Further, manipulation of miR-483-3p levels in vitro substantially modulated the capacity of adipocytes to differentiate and store lipids.  We hypothesize therefore that increased miR-483-3p expression in vivo, programmed by early life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance, thus increasing susceptibility to metabolic disease.
 
I am also interested in how pregestational obesity predisposes metabolic and cardiovascular disease in offspring. My studies in a murine model of maternal obesity during gestation currently explore intervention approaches to uncover underlying mechanisms responsible for adverse metabolic and cardiovascular outcomes and investigate the efficacy of these interventions for translational therapy.  I am currently investigating maternal metabolic and cardiovascular dysfunction as potential drivers of preeclampsia, placental dysfunction and its consequences for offspring health.
 

Expertise

Biochemistry and Molecular Biology, Epigenetics, Endocrinology, Systems Biology

Selected Publications

Loche E, Blackmore HL, Carpenter AAM, Beeson JH, Pinnock A, Ashmore TJ, Aiken
CE, de Almeida-Faria J, Schoonejans J, Giussani DA, Fernandez-Twinn DS, Ozanne
SE. Maternal Diet-Induced Obesity Programmes Cardiac Dysfunction in Male Mice
Independently of Post-Weaning Diet. Cardiovasc Res. 2018 Apr 4. doi:
10.1093/cvr/cvy082. [Epub ahead of print] PubMed PMID: 29635288.

Lowe R, Barton C, Jenkins CA, Ernst C, Forman O, Fernandez-Twinn DS, Bock C,
Rossiter SJ, Faulkes CG, Ozanne SE, Walter L, Odom DT, Mellersh C, Rakyan VK.
Ageing-associated DNA methylation dynamics are a molecular readout of lifespan
variation among mammalian species. Genome Biol. 2018 Feb 16;19(1):22. doi:
10.1186/s13059-018-1397-1. PubMed PMID: 29452591; PubMed Central PMCID:
PMC5815211.

Fernandez-Twinn DS, Gascoin G, Musial B, Carr S, Duque-Guimaraes D, Blackmore
HL, Alfaradhi MZ, Loche E, Sferruzzi-Perri AN, Fowden AL, Ozanne SE. Exercise
rescues obese mothers’ insulin sensitivity, placental hypoxia and male offspring
insulin sensitivity. Sci Rep. 2017 Mar 14;7:44650. doi: 10.1038/srep44650. PubMed
PMID: 28291256; PubMed Central PMCID: PMC5349590.

Fernandez-Twinn DS, Constância M, Ozanne SE. Intergenerational epigenetic
inheritance in models of developmental programming of adult disease. Semin Cell
Dev Biol. 2015 Jul;43:85-95. doi: 10.1016/j.semcdb.2015.06.006. Epub 2015 Jun 30.
Review. PubMed PMID: 26135290; PubMed Central PMCID: PMC5844462.

Bork-Jensen J, Scheele C, Christophersen DV, Nilsson E, Friedrichsen M,
Fernandez-Twinn DS, Grunnet LG, Litman T, Holmstrøm K, Vind B, Højlund K,
Beck-Nielsen H, Wojtaszewski J, Ozanne SE, Pedersen BK, Poulsen P, Vaag A.
Glucose tolerance is associated with differential expression of microRNAs in
skeletal muscle: results from studies of twins with and without type 2 diabetes.
Diabetologia. 2015 Feb;58(2):363-73. doi: 10.1007/s00125-014-3434-2. Epub 2014
Nov 19. PubMed PMID: 25403480; PubMed Central PMCID: PMC4287682.

Blackmore HL, Niu Y, Fernandez-Twinn DS, Tarry-Adkins JL, Giussani DA, Ozanne
SE. Maternal diet-induced obesity programs cardiovascular dysfunction in adult
male mouse offspring independent of current body weight. Endocrinology. 2014
Oct;155(10):3970-80. doi: 10.1210/en.2014-1383. Epub 2014 Jul 22. PubMed PMID:
25051449; PubMed Central PMCID: PMC4255219.

Fernandez-Twinn DS, Alfaradhi MZ, Martin-Gronert MS, Duque-Guimaraes DE,
Piekarz A, Ferland-McCollough D, Bushell M, Ozanne SE. Downregulation of IRS-1 in
adipose tissue of offspring of obese mice is programmed cell-autonomously through
post-transcriptional mechanisms. Mol Metab. 2014 Jan 20;3(3):325-33. doi:
10.1016/j.molmet.2014.01.007. eCollection 2014 Jun. PubMed PMID: 24749062; PubMed
Central PMCID: PMC3986586.

Fernandez-Twinn DS, Blackmore HL, Siggens L, Giussani DA, Cross CM, Foo R,
Ozanne SE. The programming of cardiac hypertrophy in the offspring by maternal
obesity is associated with hyperinsulinemia, AKT, ERK, and mTOR activation.
Endocrinology. 2012 Dec;153(12):5961-71. doi: 10.1210/en.2012-1508. Epub 2012 Oct
15. PubMed PMID: 23070543; PubMed Central PMCID: PMC3568261.

Ferland-McCollough D, Fernandez-Twinn DS, Cannell IG, David H, Warner M, Vaag
AA, Bork-Jensen J, Brøns C, Gant TW, Willis AE, Siddle K, Bushell M, Ozanne SE.
Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in
type 2 diabetes. Cell Death Differ. 2012 Jun;19(6):1003-12. doi:
10.1038/cdd.2011.183. Epub 2012 Jan 6. PubMed PMID: 22223106; PubMed Central
PMCID: PMC3354052.

Fernandez-Twinn DS, Ozanne SE. Early life nutrition and metabolic programming.
Ann N Y Acad Sci. 2010 Nov;1212:78-96. doi: 10.1111/j.1749-6632.2010.05798.x.
Epub 2010 Nov 11. Review. PubMed PMID: 21070247.