Cartwright Lab
Understanding Human Adipose Development in Childhood Obesity
Childhood obesity has been consistently rising, currently at a rate of approximately 1 in 5 American children, putting millions at increased risk of health complications, such as type 2 diabetes and other components of “the metabolic syndrome.” Although we are living in a world of ever-expanding treatment options for childhood obesity, including weight loss medications and weight loss surgery, substantial challenges remain. Twenty percent of all children cannot be feasibly given the most intensive weight loss treatments, nor should they – many children and teens with an elevated BMI can live healthy lives by improving their nutrition and physical activity, even if weight loss is modest. Yet the evidence shows that a significant proportion of children with obesity are unable achieve sufficient lifestyle changes, with the potential to result in severe disease burden in young adulthood.
How can we know which patients are at highest risk, and therefore should be encouraged or prioritized for intensive weight loss interventions? How can we know which patients are at low risk, or have achieved sufficient lifestyle change, so that they can avoid the risks of high-intensity interventions in favor of lifestyle maintenance? In order to answer these questions, we will need to learn much more about the consequences of obesity during childhood development and the earliest pathological changes that result in youth-onset type 2 diabetes and other metabolic disorders.
Adipose tissue (also known as fat tissue) is at the heart of metabolic syndrome pathogenesis in both adults and children. Insulin resistance and type 2 diabetes are tightly associated with adipose tissue dysfunction, including local inflammation, ECM remodeling, and fibrosis. This process has been thoroughly studied in adults, although less is known about adipose biology during childhood development.
There is strong evidence that the fundamental biology of adipose tissue undergoes dramatic changes during development, with unique stages of expansion and patterning at different phases of life. For example, adipocyte hyperplasia, or the differentiation of new fat cells, continues throughout childhood, until adipocyte number reaches a “set point” in adolescence. After that time, adipocyte number is fairly stable in adulthood, and adult adipose expansion occurs primarily via adipocyte hypertrophy.
These developmental stages have not yet been well defined on the cellular level. In order to understand disease risk in childhood obesity, we will need a much more detailed understanding of how adipose tissue develops during each stage of life, and we will need to define the earliest stages of adipose dysfunction in childhood-onset obesity. The Cartwright Lab aims to apply cutting-edge cellular techniques, including multi-omics approaches and primary cell culture, to the study of adipose tissue at all stages of childhood development. To this end, Dr. Cartwright has established an ongoing, diverse biorepository of pediatric adipose tissue, the “PAT Biobank,” to fuel research in the translational study of human adipose development.