Dear friends and colleagues,
I have recently found definite extracellular nanometer vesicles (60-70nm in diameter) being extruded from rupture-prone adipocytes and crown-like structure macrophages in the perivascular adipose tissue (PVAT) within the tunica adiposa of the aortic adventitia of the descending thoracic aortas in the obese, diabetic db/db models at 20-weeks of age as compared to controls and those treated with empagliflozin.
The PVAT of the db/db models undergoes a complete transdifferentiation from multilocular brown adipose tissue (BAT) to unilocular hypertrophic and rupture-prone unilocular adipocytes with crown-like structures.
My thoughts are that these peripherally-derived adipocyte and macrophage exosomes would be taken up by the regional vasa vasorum regional capillaries and be transported to the CNS via the systemic circulation where they could cross both the BBB and BCSFB interfaces to enter the brain along with peripherally derived cytokines/chemokines (pCC). Once within the CNS interstitium or activation of the cells within the NVU and their production of NVU-derived exosomes these peripheraly-derived EVexosomes and their miRNAs could signal the known activation of the microglia and the remodeling to reactive astrocytes that is known to exist in the db/db preclinical brain models.
Since there is bidirectional signaling between activated microglia cells (MGCs) and reactive astrocytes (rAC), it is possible that this bidirectional signaling would result in an ongoing vicious cycle and along with central nervous system cytokines/chemokines (cnsCC) result and chronic state of neuroinflammation, CNS remodeling, and impaired cognition known to be present in the obese, diabetic db/db models.
Please share with me any of your current thoughts regarding these findings and concepts in regards to proposed mechanisms.
I will look forward to your thoughts, ideas, comments, and suggestion.
With gratitude,
Melvin R. Hayden
University of Missouri School of Medicine
Columbia, Missouri USA
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