Figure Patterns of occurrence of exosome-mediated fat-brain communication and promotion of diabetic cognitive dysfunction
With the support of the National Natural Science Foundation of China (approval number: 82030026, 82100868, 82000775), Professor Bi Yan's team from the Department of Endocrinology, Gulou Hospital, Nanjing University School of Medicine, has made new progress
in the study of a new mechanism of fat-inter-brain communication mediating diabetic cognitive dysfunction 。 The research results were titled "Extracellular vesicles mediate the communication of adipose tissue with brain and promote cognitive impairment associated with insulin resistance" It was published online on September 6, 2022 in Cell Metabolism, at
Diabetes significantly increases the risk of cognitive impairment and seriously affects the healthy survival status
of the elderly.
Clinical studies have shown that controlling blood glucose does not protect cognitive function, so it is necessary to further reveal the mechanism of diabetic cognitive dysfunction and find new strategies
for treating diabetic cognitive impairment.
As a novel adipose factor, adipose tissue exosomes can participate in the biological signal transmission and metabolic regulation between adipose tissue and other peripheral tissues and organs, but it is unclear whether it can mediate the exchange of information between adipose tissue and the brain
Using fat grafting and a variety of exosome tracing techniques, the research team found that liver-derived extracellular vesicles (EVs) cannot mediate peripheral tissue and inter-brain communication, and adipose tissue-derived EVs are an important biological medium for forming communication between the two; In insulin-resistant and diabetic states, adipose tissue EVs carry contents miRNAs promote hippocampal synapse loss and cognitive impairment
The research team further used small RNA sequencing and transcriptome sequencing techniques to identify a series of key molecules that cause cognitive impairment in diabetes mellitus in EVs derived from adipose tissue, and found that the pathogenic molecule miR-9-3p, which is common to humans and mice, causes synaptic loss and thus promotes cognitive function damage
by targeting down-tuning the molecular BDNF, which is essential for the maintenance of synaptic function.
Finally, the team used virus-mediated gene silencing techniques to demonstrate that targeting adipose tissue-derived EVs or their contents, miRNAs, significantly slows diabetic cognitive dysfunction (figure
This study reveals the communication mechanism between adipose tissue and brain organs, elucidates the important role of adipose tissue-derived extracellular vesicles and their contents miRNAs in the occurrence of diabetic cognitive dysfunction, and provides new ideas
for the target of drug intervention for diabetic cognitive impairment.