Development, Epigenetics and the "Diabesity" Epidemic

Organizers: John G. Kral, MD, PhD, SUNY Downstate; Barry E. Levin, MD, UMDNJ; Gerard P. Smith, MD, Weill Cornell Medical College

The Diabetes and Obesity discussion group explores the correlation between the growing trend of obesity and rising number of those diagnosed with diabetes.

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the State University of New York (SUNY) Downstate Medical Center and the New York Academy of Sciences The State University of New York (SUNY) Downstate Medical Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The SUNY Downstate Medical Center designates this educational activity for a maximum of 7.5 AMA PRA Category 1 Credit(s) TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Speakers: Sebastien Bouret, University of Southern California; Patrick Catalano, Case Western Reserve University; Jeremy Coplan, SUNY Downstate Medical Center; Rudolph Leibel, Columbia University; Barry Levin, UMDNJ; Tanja Kral, University of Pennsylvania; John Kral, SUNY Downstate Medical Center; Peter Nathanielsz, University of Texas Health Science Center; Andreas Plagemann, University of Medicine Berlin; Robert Waterland, Baylor College of Medicine; Robert Whitaker, Temple University

Abstracts

The Potential Impact of Epigenetics on Obesity and Diabetes
Robert A. Waterland, PhD
Baylor College of Medicine

An obesity epidemic is underway in the US and many other developed countries, and is associated with an increasing prevalence of type 2 diabetes, dyslipidemia, and hypertension. It has long been presumed that genetic variation alone explains individual differences in obesity susceptibility. A complementary explanation is that individual susceptibility to obesity is determined not only by genes but also by environmental influences during development. Early environment can affect the developmental establishment of epigenetic gene regulation, providing a potential biologic mechanism for such 'metabolic imprinting' of obesity susceptibility. Epigenetics is the study of mitotically heritable alterations in gene expression potential that are not caused by changes in DNA sequence. Just as genetic variation affects individual susceptibility to obesity, so too could individual epigenetic variation. Indeed, extensive data demonstrate that epigenetic dysregulation can cause obesity. Our data in an inbred mouse model indicate that maternal obesity has an obesogenic effect on her offspring. Dietary methyl donor supplementation prevents this effect, suggesting a role for epigenetic mechanisms including DNA methylation. I will describe ongoing studies using DNA methylation microarrays to explore the hypothesis that interindividual variation in hypothalamic epigenotype is established during development and persists to affects adult body weight regulation.

Establishing Household Practices to Reduce the Intergenerational Transmission of Obesity
Robert C. Whitaker, MD, MPH
Temple University

Protection from and risk of obesity is transmitted across generations through an interaction between genes and the prenatal and postnatal environments. To break the intergenerational transmission of obesity, when during the life cycle and with what approaches would it be most helpful to intervene? The best time to intervene is the period from before children are conceived until they reach school age. Families are the social unit with greatest potential influence during this part of the life cycle because parents can establish household practices affecting c