Organotins are Potent Inducers of Vertebrate Adipogenesis – Is the Environment Making us Fat?

Featuring Bruce Blumberg, Ph.D.
Professor, Department of Developmental and Cell Biology
School of Biological Sciences
UC Irvine

Location:  California Institute for Telecommunications and Information Technology Room 3008
Free and open to the public; refreshments provided

LifeChips Seminar Series are brought to you by the IGERT fellows of the LifeChips Program.  For more information about LifeChips program, or fellowship opportunity, please visit www.lifechips.org, or send inquiries to igert@lifechips.org.

Abstract:
Obesity and metabolic syndrome diseases have exploded into an epidemic of global proportions. Consumption of calorie-dense food and diminished physical activity are accepted as causal factors for obesity. But could environmental factors expose preexisting genetic differences or exacerbate the root causes of diet and exercise? Our “obesogenhypothesis” proposes that environmental chemicals may perturb lipid homeostasis, adipocyte development, or adipose tissue function. Exposure during sensitive developmental windows results in permanent metabolic changes that increase fat storage. We identified organotinsas a novel class of obesogens and showed that the nuclear receptors, RXR and PPARγ are high-affinity molecular targets of tributyltin (TBT). RXR-PPARγ signaling is a key component in adipogenesis and the function of adipocytes. Thus, inappropriate activation of RXR-PPARγ has the potential to strike at the heart of adipose tissue homeostasis. Our results show that TBT promotes adipocyte differentiation, modulates adipogenicgenes in vivo, and increases 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. This talk will present recent results revealing details of the mechanism underlying how prenatal TBT predisposes exposed individuals to weight gain. 

About the Speaker:
Bruce Blumberg received the Ph.D. from the University of California, Los Angeles. His postdoctoral training was in the molecular embryology of vertebrate development at the Department of Biological Chemistry in the UCLA School of Medicine.  Blumberg was appointed as a staff scientist at The Salk Institute for Biological Studies, La Jolla, Calif., where he focused on the molecular endocrinology of orphan nuclear receptors and their role in embryonic development and adult physiology.  Blumberg joined the faculty at the UC Irvine in 1998, where he is currently a professor of developmental and cell biology, pharmaceutical sciences and biomedical engineering, and directs the program in the Developmental Biology of Cancer in the Chao Family Comprehensive Cancer Center. His current research focuses on the role of nuclear hormone receptors in development, physiology and disease. Particular interests include patterning of the vertebrate nervous system, the differential effects of xenobiotic exposure on laboratory model organisms compared with humans, interactions between xenobiotic metabolism, inflammation, and cancer, and the role of environmental chemicals on development, obesity and diabetes.