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, Epigenetics, Endocrinology, Systems Biology

Selected Publications

1. Fernandez-Twinn DS Hufnagel A, Blackmore HL, Ashmore TJ, Heaton RA, Jenkins B, Koulman A, Hargreaves IP, Aiken CE, Ozanne SE. Maternal but not fetoplacental health can be improved by metformin in a murine diet-induced model of maternal obesity and glucose intolerance. https://pubmed.ncbi.nlm.nih.gov/34505282/J Physiol. 2021 Sep 10. doi: 10.1113/JP281902. Epub ahead of print. PMID: 34505282.
2. Schoonejans JM, Blackmore HL, Ashmore TJ, Aiken CE, Fernandez-Twinn DS, Ozanne SE. Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner.https://pubmed.ncbi.nlm.nih.gov/34360870/ Int J Mol Sci. 2021 Jul 28;22(15):8104. doi: 10.3390/ijms22158104. PMID:34360870; PMCID: PMC8347264.
3. Bertozzi TM, Becker JL, Blake GET, Bansal A, Nguyen DK, Fernandez-Twinn DS, Ozanne SE, Bartolomei MS, Simmons RA, Watson ED, Ferguson-Smith AC. Variably methylated retrotransposons are refractory to a range of environmental perturbations.https://pubmed.ncbi.nlm.nih.gov/34326545/ Nat Genet. 2021 Aug;53(8):1233-1242. doi:10.1038/s41588-021-00898-9. Epub 2021 Jul 29. PMID: 34326545; PMCID: PMC7611517.
4. Fernandez-Twinn DS, Furse S, Chiarugi D, Koulman A, Ozanne SE Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes.https://pubmed.ncbi.nlm.nih.gov/34299070/ Int J Mol Sci. 2021 Jul 12;22(14):7452. doi: 10.3390/ijms22147452. PMID: 34299070; PMCID: PMC8306994.
5. de Almeida-Faria J, Duque-Guimarães DE, Ong TP, Pantaleão LC, Carpenter AA, Loche E, Kusinski LC, Ashmore TJ, Antrobus R, Bushell M, Fernandez-Twinn DS, Ozanne SE. Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark.https://pubmed.ncbi.nlm.nih.gov/33501603/ Diabetologia. 2021 Apr;64(4):890-902. doi: 10.1007/s00125-020-05357-4.
6. Dearden L, Buller S, Furigo IC, Fernandez-Twinn DS, Ozanne SE. Maternal obesity causes fetal hypothalamic insulin resistance and disrupts development of hypothalamic feeding pathways. https://pubmed.ncbi.nlm.nih.gov/32919096/Mol Metab. 2020 Sep 9;42:101079.
7. de Barros Mucci D, Kusinski LC, Wilsmore P, Loche E, Pantaleão LC, Ashmore TJ , Blackmore HL, Fernandez-Twinn DS , das Graças T do Carmo M & Ozanne SE (2020) Impact of maternal obesity on placental transcriptome and morphology associated with fetal growth restriction in mice.https://pubmed.ncbi.nlm.nih.gov/32203108/ Int J Obes. 44(5):1087-1096.
8. Fernandez-Twinn DS, Furse S, Jenkins B & Meek CL, Williams HEL, Smith GCS, Charnock-Jones DS, Ozanne SE & Koulman A (2020) A high-throughput platform for detailed lipidomic analysis of a range of mouse and human tissues.https://pubmed.ncbi.nlm.nih.gov/32144454/ Analytical & Bioanalytical Chemistry 412(12):2851-2862.
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.https://pubmed.ncbi.nlm.nih.gov/30293577/ Molecular metabolism 16:35-44.
10. Fernandez-Twinn DS, Hjort L, Novakovic B, Ozanne SE, Saffery R Intrauterine programming of obesity and type 2 diabetes.https://pubmed.ncbi.nlm.nih.gov/31451874/Diabetologia. 2019 Oct;62(10):1789-1801. doi: 10.1007/s00125-019-4951-9. Epub 2019 Aug 27.
PMID: 31451874