ABSTRACT
A newly recognized primary cause of obesity epidemic is the developmental programming
effects of (1) intrauterine growth-restricted (IUGR) newborns exposed in utero to
undernutrition, and (2) normal or excessive weight newborns exposed to maternal obesity
and high-fat (HF) diets. The mechanisms contributing to offspring obesity have been
extensively studied in animal models with adipose tissue identified as one of the
principal targets of programming. IUGR and HF offspring exhibit programmed adipocytes,
such that an intrinsic enhanced lipogenesis and adipocyte proliferation contribute
to the development of obesity. This is attributed to early induction of adipogenic
transcription factor peroxisome proliferator-activated receptor (PPAR)γ, whose activity
is enhanced under limited or excess nutrient availability. Nonetheless, this occurs
via different mechanisms involving PPARγ coregulators: In IUGR, it is upregulation
of coactivators, whereas in HF newborns, it is downregulation of corepressors. Thus
preventive therapeutic interventions will require target-specific modalities that
depend on the primary etiology.
KEYWORDS
Adipogenesis - lipogenesis - PPARγ - obesity
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Mina DesaiPh.D.
Associate Professor, Director of Perinatal Research, 1124 W. Carson Street
Building RB1, Room 213, Torrance, CA 90502
Email: mdesai@obgyn.humc.edu