Member Listing

Name

Denise Fernandez-Twinn
Affiliation

Department of Clinical Biochemistry, IMS -Metabolic Research Laboratories
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, Developmental Biology, Epigenetics, Endocrinology, Systems Biology
Selected Publications

1. Fernandez-Twinn DS, Sandovici I, Hufnagel A, Constância M, Ozanne SE (2022) Sex differences in the intergenerational inheritance of metabolic traits. Nature Metabolism 4(5):507-523. PMID: 35637347.
2. Hufnagel A, Dearden L, Fernandez-Twinn DS, Ozanne SE (2022) Programming of cardiometabolic health: the role of maternal and fetal hyperinsulinaemia. Journal of Endocrinology 253(2):R47-R63. PMID: 35258482; PMCID: PMC9066586.
3. Fernandez-Twinn DS, Furse S, Beeson JH, Chiarugi D, Ozanne SE, Koulman A (2022) A mouse model of gestational diabetes shows dysregulated lipid metabolism post- weaning, after return to euglycaemia. Nutrition & Diabetes. 12(1):8. PMID: 35169132; PMCID: PMC8847647.
4. Fernandez-Twinn DS, Hufnagel A, Blackmore HL, Ashmore TJ, Heaton RA, Jenkins B, Koulman A, Hargreaves IP, Aiken CE, Ozanne SE (2022) Maternal but not fetoplacental health can be improved by metformin in a murine diet-induced model of maternal obesity and glucose intolerance. Journal of Physiology 600(4):903-919. PMID: 34505282; PMCID: PMC7612651.
5. Pantaleão LC, Inzani I, Furse S, Loche E, Hufnagel A, Ashmore T, Blackmore HL, Jenkins B, Carpenter AAM, Wilczynska A, Bushell M, Koulman A, Fernandez- Twinn DS, Ozanne SE (2022) Maternal diet-induced obesity during pregnancy alters lipid supply to mouse E18.5 fetuses and changes the cardiac tissue lipidome in a sex- dependent manner. Elife 11:e69078. PMID: 35025731; PMCID: PMC8794468.
6. Bertozzi TM, Becker JL, Blake GET, Bansal A, Nguyen DK, Fernandez-Twinn DS, Ozanne SE, Bartolomei MS, Simmons RA, Watson ED, Ferguson-Smith AC (2021) Variably methylated retrotransposons are refractory to a range of environmental perturbations. Nature Genetics 53(8):1233-1242. PMID: 34326545; PMCID: PMC7611517.
7. Schoonejans JM, Blackmore HL, Ashmore TJ, Aiken CE, Fernandez-Twinn DS, Ozanne SE (2021) Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner. International Journal of Molecular Science 22(15):8104. PMID: 34360870; PMCID: PMC8347264.
8. Fernandez-Twinn DS, Hjort L, Novakovic B, Ozanne SE, Saffery R (2019) Intrauterine programming of obesity and type 2 diabetes. Diabetologia 62(10):1789-1801. doi: 10.1007/s00125-019-4951-9. PMID: 31451874; PMCID: PMC6731191.
9. Beeson JH, Blackmore HL, Carr SK, Dearden L, Duque-Guimarães DE, Kusinski LC, Pantaleão LC, Pinnock AG, Aiken CE, Giussani DA, Fernandez-Twinn DS, Ozanne SE (2018) Maternal exercise intervention in obese pregnancy improves the cardiovascular health of the adult male offspring. Molecular Metabolism 16:35-44. PMID: 30293577; PMCID: PMC6157615.
10. 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 (2018) Ageing associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species. Genome Biology 19(1):22. PMID: 29452591; PMCID: PMC5815211.
Emaildf220@cam.ac.uk