Al.Pagesubsequent reduced Mash1/Ngn3 expression. They have further explored this pathway in FR offspring using hypothalamic NSCs. FR fetuses exhibit reduced NSC migration (from the periventricular region to the ARC) in vivo, with reduced proliferation and neuronal differentiation in vitro. Importantly, even in culture media outside the fetal environment, FR NSCs are programmed to preferentially differentiate to appetite as compared to satiety neurons.69,70 In addition to programmed appetite/satiety, these studies indicate that adipogenesis is also a contributory factor to the development of programmed obesity. Increases in adipogenesis and fat mass occur pre- and postnatally, though some adipogenesis continues during adulthood. Adipose tissue grows through both cell hyperplasia and hypertrophy. The process of adipogenesis involves differentiation of fibroblasts and pre-adipocytes to mature fatstoring adipocytes. The differentiation pathway is highly organized, with precisely controlled expression of a cascade of transcription factors. Of these, the principal GW9662 web adipogenic transcription factors PPAR (peroxisome proliferator-activated receptor) and C/EBP (CCAAT enhancer inding protein) promote adipogenesis. The downstream target of PPAR is the lipogenic transcription factor SREBP1 (sterol regulatory element inding protein), which facilitates lipogenesis (Fig. 3B). In these studies, both FR and HF offspring exhibit enhanced adipogenesis. In both offspring, there is early induction of the adipogenic signaling cascade promoting fat storage, as evidenced by increased gene expression of PPAR, C/EBP, and SREBP1, as well as increased de novo fatty acid synthesis. Utilizing primary preadipocyte and adipocyte cultures, Desai and Ross have further explored whether the increased adipogenic potential of FR adipocytes is due to intrinsic cellular changes. FR preadipocytes have comparatively increased proliferative potential and, when allowed to differentiate to mature adipocytes, exhibit higher PPAR expression with greater lipid content than those of controls.71,72 Importantly, FR preadipocytes and adipocytes are more sensitive to insulin, a potent growth factor during fetal life. Overall, FR adipocytes in culture retain the phenotype of enhanced adipogenesis and lipogenesis, evidenced by growth in culture, as well as enzyme/signaling expression. Programmed hyperphagia and adiposity are secondary to enhanced appetite and impaired satiety responses, intrinsic traits of increased adipocyte differentiation, and enhanced propensity for fat storage. These phenotypes result from alterations in stem cell precursors of both appetite/satiety neurons and adipocytes, changes that promote offspring obesity. Early modifications of the maternal nutrient environment may prevent altered development and regulation of appetite and adipogenesis. Breast feeding: molecules, nutrients, and context Nancy F. Krebs (University of Colorado School of Medicine) discussed the relationship between bioactive components in breast milk and infant growth, with implications for lifelong adipogenesis. Rapid Pyrvinium embonate side effects weight gain during the first weeks to months of post-natal life is associated with later obesity.73 The growth acceleration hypothesis proposes that rapid growth programs infant metabolism to be susceptible to obesity and comorbidities later in life.74 Abundant epidemiologic data support the importance of a critical post-natal window,Ann N Y Acad Sci. Author manuscript; available in PM.Al.Pagesubsequent reduced Mash1/Ngn3 expression. They have further explored this pathway in FR offspring using hypothalamic NSCs. FR fetuses exhibit reduced NSC migration (from the periventricular region to the ARC) in vivo, with reduced proliferation and neuronal differentiation in vitro. Importantly, even in culture media outside the fetal environment, FR NSCs are programmed to preferentially differentiate to appetite as compared to satiety neurons.69,70 In addition to programmed appetite/satiety, these studies indicate that adipogenesis is also a contributory factor to the development of programmed obesity. Increases in adipogenesis and fat mass occur pre- and postnatally, though some adipogenesis continues during adulthood. Adipose tissue grows through both cell hyperplasia and hypertrophy. The process of adipogenesis involves differentiation of fibroblasts and pre-adipocytes to mature fatstoring adipocytes. The differentiation pathway is highly organized, with precisely controlled expression of a cascade of transcription factors. Of these, the principal adipogenic transcription factors PPAR (peroxisome proliferator-activated receptor) and C/EBP (CCAAT enhancer inding protein) promote adipogenesis. The downstream target of PPAR is the lipogenic transcription factor SREBP1 (sterol regulatory element inding protein), which facilitates lipogenesis (Fig. 3B). In these studies, both FR and HF offspring exhibit enhanced adipogenesis. In both offspring, there is early induction of the adipogenic signaling cascade promoting fat storage, as evidenced by increased gene expression of PPAR, C/EBP, and SREBP1, as well as increased de novo fatty acid synthesis. Utilizing primary preadipocyte and adipocyte cultures, Desai and Ross have further explored whether the increased adipogenic potential of FR adipocytes is due to intrinsic cellular changes. FR preadipocytes have comparatively increased proliferative potential and, when allowed to differentiate to mature adipocytes, exhibit higher PPAR expression with greater lipid content than those of controls.71,72 Importantly, FR preadipocytes and adipocytes are more sensitive to insulin, a potent growth factor during fetal life. Overall, FR adipocytes in culture retain the phenotype of enhanced adipogenesis and lipogenesis, evidenced by growth in culture, as well as enzyme/signaling expression. Programmed hyperphagia and adiposity are secondary to enhanced appetite and impaired satiety responses, intrinsic traits of increased adipocyte differentiation, and enhanced propensity for fat storage. These phenotypes result from alterations in stem cell precursors of both appetite/satiety neurons and adipocytes, changes that promote offspring obesity. Early modifications of the maternal nutrient environment may prevent altered development and regulation of appetite and adipogenesis. Breast feeding: molecules, nutrients, and context Nancy F. Krebs (University of Colorado School of Medicine) discussed the relationship between bioactive components in breast milk and infant growth, with implications for lifelong adipogenesis. Rapid weight gain during the first weeks to months of post-natal life is associated with later obesity.73 The growth acceleration hypothesis proposes that rapid growth programs infant metabolism to be susceptible to obesity and comorbidities later in life.74 Abundant epidemiologic data support the importance of a critical post-natal window,Ann N Y Acad Sci. Author manuscript; available in PM.