Researchers at Children’s Hospital of Philadelphia (CHOP) have unveiled new insights into how a specific molecule, miR-6236, regulates insulin sensitivity, providing potential therapeutic targets for obesity-related type 2 diabetes. Their findings, published in Nature Communications, transitioned from preclinical animal models to human studies, highlighting significant implications for future treatments.
ATMs can prevent obesity-related metabolic diseases
The study focuses on adipose tissue macrophages (ATMs), immune cells crucial for maintaining healthy adipose tissue or body fat. These cells secrete vesicles containing vital signaling molecules while performing their functions. Previous research hinted that normal ATM activities could prevent obesity-related metabolic diseases, though the mechanisms remained unclear.
The breakthrough came with the identification of miR-6236, a micro RNA that regulates gene expression. Researchers used preclinical mouse models to study miR-6236’s role in mitigating obesity and type II diabetes at the cellular level.
According to Dr. David A. Hill, senior author of the study, the microRNA in question was previously mischaracterized. However, Hill explained that through experiments on mice and analysis of a large human dataset concerning metabolic disease risk, researchers confirmed its significant role in insulin signaling regulation.
The study demonstrated that miR-6236 is secreted by ATMs in response to obesity. When miR-6236 was removed in mouse models, several adverse effects occurred, such as insulin resistance, hyperinsulinemia, hyperglycemia, and hyperlipidemia. The research revealed that miR-6236 enhances insulin sensitivity by inhibiting PTEN, a gene associated with obesity and type 2 diabetes.
miR-6236 secretion during obesity to enhance insulin sensitivity
It appears that ATMs secrete miR-6236 during obesity to improve insulin sensitivity and reduce the risk of hyperglycemia and glucose intolerance. Low levels of miR-6236 may thus indicate a higher risk of diabetes.
Hill proposed that the findings could lead to the creation of synthetic micro RNAs. He anticipates that in the near future, synthetic micro RNA development may advance, potentially including miR-6236 for enhancing insulin sensitivity and reducing hyperglycemia.
This study underscores the central role of the immune system in maintaining a healthy metabolism and opens up promising avenues for developing new treatments for obesity-related type 2 diabetes.
