Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Supersized: epigenetics in very large mammal models (#55)

Katherine Samaras 1 2
  1. Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Department of Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia

Obesity has reached epidemic proportions in western and developing countries and is associated with accelerated development of type 2 diabetes mellitus, atherothrombotic cardiac disease and cancer and undermines human health and longevity. In particular, these health risks are associated with expansion of visceral abdominal adipose tissue (VAT), whereas expansion of subcutaneous adipose depots appears health outcome-benign. Twin studies have demonstrated that genetic factors explain the majority of differences between individuals for obesity and adipose distribution, however gene-environment interactions that protect some individuals from manifesting their genetic obesity predisposition and other that magnify it have been demonstrated. Advances in the understanding DNA regulation (particularly the epigenetic machinery that regulates gene transcription) and technologies that permit measurement of epigenetic modification, allow examination of site-specific differences in adipocytes in obese and lean humans, to further understand how obesity impacts human health.

Every human cell type shares the same DNA code. The epigenome enforces, and sequentially restricts, cell-specific genetic expression in development cellular maintenance and function and cell death upon this common genome. The best-described methods of the epigenetic regulatory machinery that restrict or promote DNA transcription are DNA methylation, histone modification and non-coding RNA. The association of epigenomic marks with functional transcriptional outcomes have been established in numerous studies and may be integral to understanding how the expression of the genetic code can be modified in obesity. The advent of next generation sequencing technology has enabled genome wide determination of epigenomic marks, allowing examination of epigenomic differences in health and in disease.

Whole genome bisulphite sequencing is the standard methodology for whole methylome analysis and has been used to comprehensively identify the important characteristics of DNA methylation in different cells.

Epigenetic modification in human obesity will be discussed, with reference to existing and novel data in lean and obese (supersized) humans.