Xingxing Kong, MD, PhD
Assistant Professor of Pediatrics
Dr. Xingxing Kong studies adipose tissue biology to find obesity interventions that could help pediatric patients achieve long-term health. Her work reveals genetic factors controlling fat tissue behavior, which influences energy homeostasis, metabolic processes, and the development of obesity.
According to the Centers for Disease Control and Prevention, the rate of childhood obesity has tripled since 1970, now affecting about 1 in every 5 children. In addition to taking a toll on overall health and wellness, obesity can lead to hypertension, stroke, cardiovascular disease, and type 2 diabetes. Dr. Kong hopes to improve outcomes in these complications by pinpointing, and eventually influencing, the deep cellular processes that promote obesity.
When humans can’t support adequate thermogenesis—the dissipation of calories as heat—they are more likely to become obese. The medical community has long accepted the link between obesity and thermogenesis, but the mechanisms behind the link remain mysterious. Dr. Kong’s studies pinpoint factors driving the connection.
Dr. Kong and her team established that animals lacking the protein-coding gene interferon regulatory factor 4 (IRF4) experience obesity, insulin resistance, and reduced thermogenic gene expression. The finding inspired the team to explore IRF4’s influence on thermogenesis in greater detail. Read more in Interferon Regulatory Factor 4 Regulates Obesity-Induced Inflammation Through Regulation of Adipose Tissue Macrophage Polarization, published in Diabetes.
As Dr. Kong and her team studied IRF4, they found that it interacts with a co-activator to coordinate adaptive thermogenesis, a process critical in obesity outcomes. The study suggested that expression of IRF4 promotes thermogenesis and leanness, while absence of IRF4 reduces thermogenesis and leads to obesity. Read more in IRF4 Is a Key Thermogenic Transcriptional Partner of PGC-1α, published in Cell.
The study was one of the first to offer a reason why some people, through thermogenic inefficiency, might be genetically predisposed to obesity.
Building on her compelling findings, Dr. Kong continues to explore the biology of fat tissue as well as IRF4 and its impact on thermogenesis and obesity. While exploring IRF4’s role in exercise-induced thermogenesis, Dr. Kong and her team found a surprising level of crosstalk between brown adipose tissue (BAT) and skeletal muscle. In the study, the crosstalk, which involves IRF4 and secreted proteins, ultimately determined exercise capacity. Read more in Brown Adipose Tissue Controls Skeletal Muscle Function Via the Secretion of Myostatin, published in Cell Metabolism.
Dr. Kong’s team believes elucidating the processes driving naturally induced thermogenesis will reveal ways to selectively induce thermogenesis, giving physicians an unprecedented ability to influence obesity development.
“Eventually, we believe that the detailed study of IRF4 in the context of metabolism will yield critical insights that can be exploited therapeutically in the fight against obesity and type 2 diabetes,” says Dr. Kong.
