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Obesogens, stem cells and the maternal programming of obesity

Published online by Cambridge University Press:  04 November 2010

B. Blumberg
B. Blumberg*
Affiliation:
Department of Developmental and Cell Biology and Pharmaceutical Sciences, University of California, Irvine, Biological Sciences 3, Irvine, CA, USA
*
*Address for correspondence: B. Blumberg, Department of Developmental and Cell Biology and Pharmaceutical Sciences, University of California, Irvine, 2011 Biological Sciences 3, Irvine, CA 92697-2300, USA. (Email [email protected])
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Abstract

Obesity and metabolic syndrome diseases have exploded into a global epidemic. Consumption of calorie-dense food and diminished physical activity are the generally accepted causes for obesity. But, could environmental factors expose preexisting genetic differences or exacerbate the root causes of diet and exercise? The environmental obesogen model proposes that chemical exposure during critical developmental stages influences subsequent adipogenesis, lipid balance and obesity. Obesogens are chemicals that stimulate adipogenesis and fat storage or alter the control of metabolism, appetite and satiety to promote weight gain. Tributyltin (TBT) is a high-affinity agonistic ligand for the retinoid X receptor (RXR) and peroxisome proliferator activated receptor gamma (PPARγ). RXR-PPARγ signaling is a key component in adipogenesis and the function of adipocytes; activation of this heterodimer increases adipose mass in rodents and humans. Thus, inappropriate activation of RXR-PPARγ can directly alter adipose tissue homeostasis. TBT exposure promoted adipocyte differentiation, modulated adipogenic genes and increased adiposity in mice after in utero exposure. These results suggest that organotin exposure is a previously unappreciated risk factor for the development of obesity and related disorders. Based on the observed effects of TBT on adipogenesis, we hypothesized that organotin exposure during prenatal adipose tissue development would create an environment that led to more adipocytes. We observed that the multipotent stromal cell compartment was altered by prenatal TBT exposure leading to an increased number of preadipocytes. This increase in the number of preadipocytes could correspondingly increase the steady state number of adipocytes in the adult, which could favor the development of obesity over time.

Keywords

adipocyteendocrine disruptermultipotent stromal cellobesityobesogenorganotinPPARγ
Type
Themed Content: Role of Environmental Stressors in the Developmental Origins of Disease
Information
Journal of Developmental Origins of Health and Disease , Volume 2 , Issue 1: Including Themed Content: Role of Environmental Stressors in the Developmental Origins of Disease , 23 February 2011 , pp. 3 - 8
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2010

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