a1 Early Life Nutrition Research Unit, Academic Child Health, Division of Human Development and Nottingham Respiratory Medicine Biomedical Research Unit, School of Clinical Sciences, Queen's Medical Centre, University Hospitals, Nottingham NG7 2UH, UK
The emerging role of adipose tissue as a dynamic endocrine organ with an extent of anatomical and physiological plasticity has generated numerous studies linking early-life events with long-term alterations in adipose tissue structure and function. Coupled with increasing rates of human obesity, which cannot be explained without some genetic component, the role of early programming of adipose tissue may provide an insight into potential mechanisms. The developmental origins of health and disease hypothesis investigates the potential association between a compromised fetal and postnatal environment and later disease, such as obesity and type 2 diabetes, in the offspring. A number of animal models have been developed to examine potential mechanisms that drive these physiological changes, including rodent and large-mammal models that provide mechanistic insights into the epidemiological findings. In utero challenges such as under- or over-provision of nutrients, placental insufficiency and glucocorticoid infusion, as well as postnatal nutritional challenges, can all result in the long-term programming of adipose tissue abundance and function. A range of hormones, enzymes, transcription factors and other metabolic signalling molecules have been implicated in adverse adipose tissue development, including leptin, glucocorticoids, members of the PPAR family, fatty acid-binding proteins and adipokines. The long-term structural and physiological consequences associated with these molecular and cellular changes are less well described. The experimental models, potential mechanisms and regulators of the early programming of adipose tissue in large mammalian species will be summarised in the present review.
(Online publication September 01 2009)
p1 Present address: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leics LE12 5RD.