We study adipose tissue biology to find obesity interventions that could help pediatric patients achieve long-term health. Our work reveals genetic factors controlling fat tissue behavior, which influences energy homeostasis, metabolic processes, and the development of 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. We 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.
We also found that IRF4 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.
We explored the biology of fat tissue as well as IRF4 and its impact on thermogenesis and obesity. We hope to find out if IRF4 plays a role in exercise-induced thermogenesis, a process triggered by specific protein secretions. Our work has illuminated an unsuspected level of inter-organ cross-talk between brown adipose tissue (BAT) and skeletal muscle, involving the transcription factor IRF4 and the secreted protein myostatin. We further discovered brown adipose tissue can secrete significant quantities of myostatin into the blood in response to warming, a situation that is mimicked by deleting IRF4 in BAT. Conversely, bariatric surgery increases BAT activity, while also reducing serum myostatin and restoring ribosomal gene expression in muscle.
