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.
Loche E, Blackmore HL, Carpenter AAM, Beeson JH, Pinnock A, Ashmore TJ, Aiken
Lowe R, Barton C, Jenkins CA, Ernst C, Forman O, Fernandez-Twinn DS, Bock C,
Fernandez-Twinn DS, Gascoin G, Musial B, Carr S, Duque-Guimaraes D, Blackmore
Fernandez-Twinn DS, Constância M, Ozanne SE. Intergenerational epigenetic
Bork-Jensen J, Scheele C, Christophersen DV, Nilsson E, Friedrichsen M,
Blackmore HL, Niu Y, Fernandez-Twinn DS, Tarry-Adkins JL, Giussani DA, Ozanne
Fernandez-Twinn DS, Alfaradhi MZ, Martin-Gronert MS, Duque-Guimaraes DE,
Fernandez-Twinn DS, Blackmore HL, Siggens L, Giussani DA, Cross CM, Foo R,
Ferland-McCollough D, Fernandez-Twinn DS, Cannell IG, David H, Warner M, Vaag
Fernandez-Twinn DS, Ozanne SE. Early life nutrition and metabolic programming.