UPMC Children’s Pediatric Endocrinology Research Team Publishes New Study in Journal of Clinical Investigation on FoxO1 Transcription Factor

July 26, 2022

Pediatric endocrinology researchers from UPMC Children’s Hospital of Pittsburgh and the Department of Pediatrics at the University of Pittsburgh School of Medicine published findings in the Journal of Clinical Investigation on their continuing exploration of the FoxO1 transcription factor and its function in mediating insulin resistance and hepatic inflammation. 

The study was led by senior author H. Henry Dong, PhD, professor of Pediatrics in the Division of Pediatric Endocrinology.

Dr. Dong’s laboratory works to characterize the insulin-Akt-FoxO1 signaling pathway in glucose and lipid metabolism in the liver and extrahepatic tissues. His investigations are providing insight into the molecular events that link insulin resistance to metabolic abnormalities, providing a knowledge base for the development of small molecule drugs for better clinical management of diabetic dyslipidemia in patients with morbid obesity and type 2 diabetes.

In the newly published paper1 titled “Myeloid FoxO1 Depletion Attenuates Hepatic Inflammation and Prevents Nonalcoholic Steatohepatitis,” Dr. Dong and colleagues found that hepatic inflammation resulting from overnutrition is influenced by macrophages that have increased levels of activity of the FoxO1 transcription factor.

The team found that in obese mice, macrophages in the liver showed significant upregulation of FoxO1 activity, which leads to a proinflammatory state with concomitant fibrosis and steatosis.

In experiments with a knockout mouse model in which FoxO1 activity is suppressed in hepatic macrophages, the animal models were protected from these effects when fed a diet that induced non-alcoholic steatohepatitis (NASH) – a comorbidity that is prevalent in patients with morbid obesity or type 2 diabetes.

With these and other numerous new findings detailed the paper’s results, Dr Dong and colleagues’ results point toward FoxO1 being a potential druggable target for mitigating inflammatory effects in NASH.

Furthermore, results from the study add significant new insights into the critical role played by FoxO1 in the setting of obesity, metabolic disease, and insulin resistance.

Learn more about Dr. Dong and his research.

Read the full paper using the reference below.

1. Lee S, Usman TO, Yamauchi J, Chhetri G, Wang X, Coudriet GM, Zhu C, Gao J, McConnell R, Krantz K, Rajasundaram D, Singh S, Piganelli J, Ostrowska A, Soto-Gutierrez A, Monga SP, Singhi AD, Muzumdar R, Tsung A, Dong HH. Myeloid FoxO1 Depletion Attenuates Hepatic Inflammation and Prevents Nonalcoholic Steatohepatitis. J Clin Invest. 2022 Jul 15; 132(14): e154333.