Developmental origins of obesity: programmed adipogenesis

Abstract

The metabolic syndrome epidemic, including a marked increase in the prevalence of obesity and gestational diabetes mellitus (GDM) among pregnant women, represents a significant public health problem. There is increasing recognition that the risk of adult obesity is clearly influenced by prenatal and infant environmental exposures, particularly nutrition. This tenet is the fundamental basis of developmental programming. Low birth weight, together with infant catch-up growth, is associated with a significant risk of adult obesity. Exposure to maternal obesity, with or without GDM, or having a high birth weight also represents an increased risk for childhood and adult obesity. Animal models have replicated human epidemiologic findings and elucidated potential programming mechanisms that include altered organ development, cellular signaling responses, and epigenetic modifications. Prenatal care has made great strides in optimizing maternal, fetal, and neonatal health, and now has the opportunity to begin interventions which prevent or reduce childhood/adult obesity. Guidelines that integrate optimal pregnancy nutrition and weight gain, management of GDM, and newborn feeding strategies with long-term consequences on adult obesity, remain to be elucidated.

Figure 1. Developmental Programming of Obesity

Altered maternal nutrition, hormonal or metabolite milieu impacts fetal growth resulting in low or high birth weight newborns. As a result of this growth deviation in utero combined with accelerated/similar postnatal growth causes enhanced adipogenesis, resulting in childhood and adult obesity. Obesity in turn leads to insulin resistance and inflammation.

Figure 2. Increased Adipogenesis Mediated Diabetes Mellitus

Adipogenesis is a process of cell differentiation by which preadipocytes become adipocytes. Increased nutrient supply or elevated hormonal levels (e.g., insulin, corticosterone, IGF1) stimulate cell proliferation and differentiation. Induction of adipocyte differentiation is facilitated by adipogenic transcription factor (PPARg) and fat storage by lipogenic transcription factor (SREBP1). Increased adipogenesis is associated with increased macrophage infiltration and increased secretion of pro-diabetic (TNFα, IL-6, leptin, visfatin) with decreased secretion of anti-diabetic (adiponectin) adipocytokines.