ISORAM Day 1: FTO, Micro RNA, KO-Mice, and Big Fat Cells

Yesterday, the 2nd International School on Obesity Research And Management (ISORAM), kicked off with a series of brief overviews of the basic sciences in obesity.

Yvonne Böttcher (Leipzig) provided an update of obesity genetics. Although there are now 33 common genetic risk variants for BMI, even when combined, these markers explain only a small proportion (<10%) of the total heritability of obesity. Perhaps, there is a bigger than expected role for rare and low frequency genetic variants with highly penetrant effects (albeit in a smaller number of obese people). In addition, there may also be an important role for deletions and copy number variability that may contribute to the obesity phenotype.

Nora Klöting (Leipzig) explained how animal models are essential to better understanding of the pathogenesis, genetics and mechanisms of human obesity as the basic physiology of molecules associated with obesity and obesity related diseases can frequently only be investigated in such models. In fact, it was the study of animal models of obesity that led to the discovery of leptin and a host of other important molecules that regulate energy homeostasis and metabolism. There is no doubt that generation and characterization of transgenic animal models will continue adding pieces to the
puzzle, allowing us to better understand the pathophysiology of adipose tissue, obesity, lipodystrophy, and insulin resistance.

Maria Keller (Leipzig) next spoke about the importance of epigenetics, which may explain many of the gene x environment interactions. Thus, while these interactions do not change the genetic code, they very can very much influence tissue specific gene expression patterns that significantly alter metabolism and other function. Mechanisms that can lead to epigenetic modification of genes include DNA methylation, micro RNAs, or modifications of histonses. These mechanisms may not only play a role in fetal programming but may also be influenced by factors such as diet, physical activity, or environmental toxins.

Isabel Wagner (Leipzig) rounded off this first session by discussing the many roles of adipose tissue, particularly in the development of childhood obesity. She pointed out that fat mass can increase both by hyperplasia (increase in cell number) and hypertrophy (increase in cell size), the latter being most often associated with insulin resistance, adipose tissue inflammation, and other alterations that may contribute to obesity related health problems. The many bioactive adipokines, secreted by fat cells can act locally and systemically through autocrine, paracrine and endocrine effects that can modulate a wide range of bodily functions including appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure and lipid metabolism. In addition, adipocytes are also a major site for the metabolism of sex steroids and glucocorticoids, which can contribute to health and disease.

Other presentations on day one of ISORAM include talks by David Petroff (Leipzig) on the use of armband monitors to directly measure activity and energy expenditure, Deborah Bade Horn (Houston) on removing barriers and promoting physical activity in the complex patient with severe obesity, Francis Finucane (Galway, Ireland) on the need for more studies on the ‘effectiveness’ of exercise interventions (or their lack thereof), rather than simply doing more studies to show its ‘efficacy’, which is well known and appreciated, and by Marlene Alexandrowitz (Copenhagen) on the challenges facing the development and deployment of specialized equipment for individuals of different body sizes at home, in health care settings and the workplace.

Lake Louise, Alberta