Mechanisms by which poor early growth programs type-2 diabetes, obesity and the metabolic syndrome.
Fetal programming is gaining momentum as a highly documented phenomenon which links poor early growth to adult disease. It is backed up by large cohorts in epidemiological studies worldwide and has been tested in various animal models. The root causes of programming link closely with maternal condition during pregnancy, and therefore the fetal environment. Suboptimal fetal environments due to poor or inadequate nutrition, infection, anemia, hypertension, inflammation, gestational diabetes or hypoxia in the mother expose the fetus to hormonal, growth factor, cytokine or adipokine cues. These in turn act to alter metabolic, immune system, vascular, hemodynamics, renal, growth and mitochondrial parameters respectively and most evidently in the later stages of life where they impact on the individual as poor glucose homeostasis, insulin resistance, type 2 diabetes, hypertension, cardiovascular disease, obesity and heart disease. These events are compounded by over-nutrition or lifestyle choices which are in conflict with the programming of the fetus. We and others have utilised various species to test the early life programming hypothesis and to identify key molecular mechanisms. With parallel studies of human cohorts, these molecular markers can be validated as realistic targets for intervention.
Fernandez-Twinn
D S
DS
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom. df220@cam.ac.uk
Ozanne
S E
SE
D000222:Adaptation, Physiological; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000196:embryology / Q000209:etiology*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000503:physiopathology; D006801:Humans; D024821:Metabolic Syndrome / Q000196:embryology / Q000209:etiology*; D023421:Models, Animal; D009765:Obesity / Q000196:embryology / Q000209:etiology*; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena; D013312:Stress, Physiological / Q000150:complications*