The "adipose tissue expandability" hypothesis: a potential mechanism for insulin resistance in obese youth

Obesity has become a major global health challenge of the 21st century, as it is associated with the onset of type 2 diabetes (T2D) and cardiovascular complications, even at a very early age in life. The root causes of pediatric obesity remain incompletely understood. The obesity epidemic together with the relationship of obesity to the growing population burden of chronic disease presents unprecedented research opportunities and challenges. Decades of obesity-related research funded by governments around the world have yielded many important discoveries about both etiological pathways and preventive or therapeutic interventions. Yet, there is a sense that the problem is outpacing these research efforts. Obesity poses a significant risk for the development of cardiovascular disease (CVD), diabetes and certain cancers thereby shortening life expectancy. Nevertheless, many obese individuals do not develop any of these comorbidities. One hypothesis explaining this dilemma is that total body fat is not the culprit of adverse health in obesity rather the relative proportion of lipids in various fat depots is what determines the metabolic risk. In this review, we describe the role of altered fat partitioning in youth onset obesity and its relation to fatty liver and T2D during adolescence.