title: Mechanisms of developmental programming of the metabolic syndrome and related disorders.
abstract: There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1) thrifty phenotype; (2) postnatal accelerated or catch-up growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.
authors.affiliation: Zhong-Cheng Luo, Lin Xiao, Department of Obstetrics and Gynecology, CHU Sainte Justine, University of Montreal, Quebec H3T 1C5, Canada.
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Luo
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.forename: Anne-Monique
authors.initials: AM
authors.lastname: Nuyt