Epidemiological studies indicate that low birth weight is associated with adult visceral obesity, a hallmark of metabolic syndrome suggesting regional programming of preadipocytes (PA) in the presence of poor fetal nutrition. No studies exist to indicate underlying mechanisms. RATIONALE: Fetal adipose tissue (AT) is primarily deposited in the final trimester and involves PA differentiation. Understanding the differences in fetal PA differentiation among depots is important since they may program fat distribution patterns. We will use a primate model with recognized similarities to humans and analyze cells from tissues impossible to acquire in humans. We provide preliminary data from omental (OM) and subcutaneous (SQ) depots derived from near term baboon fetuses of control mothers fed ad libitum (CTR) or maternal nutrient restriction (MNR) fed 70% of food fed CTR throughout pregnancy. HYPOTHESES: We hypothesize that 30% global MNR 1) inhibits PA differentiation more and increases sensitivity to adipogenesis-stimulating factors less in SQ than OM fat;2) decreases local IGF-I bioavailability in SQ but not OM fat via an increase of IGF binding proteins-2, - 4, and -5 relative to their protease pregnancy associated plasma protein-A (PAPP-A);and 3) leads to depot- distinctive expression profiles of other paracrine modulators of adipogenesis that are specific targets of MNR.
SPECIFIC AIMS : We will use our baboon MNR model to 1) assess effects of MNR on regional in vitro PA differentiation and 2) determine the role of the local IGFBPs/PAPP-A system and other mechanisms. APPROACH: We will use AT samples from CTR and MNR fetuses from a P01 currently funded for studies on placenta, brain, and kidney but containing no studies on PA. Pregnant baboons are randomly assigned to CTR or MNR. At C-Section at 0.9 gestation, fetal OM, SQ abdominal and femoral AT are dissected and cultured to determine PA differentiation by staining for lipid accumulation, secreted proteins (by ELISA), and expression profiles (by gene arrays). OBJECTIVES: Studies on effects of maternal diet on regional adipogenesis are vital to understand mechanisms of fat distribution patterns. INNOVATION: The study's novelty is lies in the combination of complete lack of data on fetal adipogenesis in developing depots, the model, and its mechanistic approaches. ENVIRONMENT: The environment has the resources needed. Tissues are available at no cost. IMPACT AND LAY SUMMARY: A poor prenatal nutritional environment alters reactivity of fat cell precursors in different sites differently and leads to a tendency to store fat preferentially inside the abdomen increasing risk for adult chronic diseases. It is important to identify developmental mechanisms involved as they emerge to develop diagnostic, preventative and therapeutic strategies.
IMPACT AND LAY SUMMARY: A poor prenatal nutritional environment alters reactivity of fat cell precursors in different sites differently and leads to a tendency to store fat preferentially inside the abdomen increasing risk for adult chronic diseases. It is important to identify developmental mechanisms involved as they emerge to develop diagnostic, preventative and therapeutic strategies.
| Tchoukalova, Y D; Krishnapuram, R; White, U A et al. (2014) Fetal baboon sex-specific outcomes in adipocyte differentiation at 0.9 gestation in response to moderate maternal nutrient reduction. Int J Obes (Lond) 38:224-30 |
