Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells

Abstract

Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue (AT). Yet, the role of adipocyte-derived EVs in pancreatic β cells remains to be determined. Here, we explored the effects of EVs released from adipocytes isolated from both rodents and humans and human AT explants on survival and function of pancreatic β cells and human pancreatic islets. EVs from healthy 3T3-L1 adipocytes increased survival and proliferation and promoted insulin secretion in INS-1E β cells and human pancreatic islets, both those untreated or exposed to cytokines or glucolipotoxicity, whereas EVs from inflamed adipocytes caused β cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, whereas EVs from obese AT explants were harmful for human EndoC-βH3 β cells. We observed differential expression of miRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of β cell genes, adipokines, and cytokines in recipient β cells. These in vitro results suggest that, depending on the physiopathological state of AT, adipocyte-derived EVs may influence β cell fate and function.

Obesity and Pancreatic Cancer: Insight into Mechanisms

“…Generally, AT can influence PDAC development systemically via soluble mediators that are released from distant (visceral) fat depots and reach the pancreatic microenvironment through the systemic circulation or via paracrine effects elicited by intrapancreatic adipocytes (see below) [63,64]. A mechanism that is receiving increasing attention is communication via extracellular vesicles from adipocytes that can fuse with target cells in the pancreas [65][66][67]. It has been shown recently that adipocytes experience strong energetic stress during obesity, which resulted in the release of small extracellular vesicles harboring respiration-competent, but oxidatively damaged, mitochondrial fragments, which access the systemic circulation and are internalized by cardiomyocytes [68].…”

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

“… 344 MiRNAs profiles in adipocyte-derived exosomes vary under different physiopathological conditions of adipose tissue. 345 Adipocyte-derived exosomal miRNAs, such as miR-34a, 346 miR-222, 347 miR-27a, 348 and miR-802-5p 85 can promote IR via regulating Krüppel-like factor 4 (KLF4), insulin receptor substrate 1 (IRS1), peroxisome proliferator-activated receptor γ (PPARγ), and HSP60. Hepatocyte uptake of exosomes from adipocytes in obese mice containing less miR-141-3p than that in healthy mice, and the reduced absorption of miR-141-3p resulted in reduced glucose uptake in hepatocytes.…”

Clinical Translational Potentials of Stem Cell-Derived Extracellular Vesicles in Type 1 Diabetes

“…Recently, Gesmundo et al. reported that adipocyte-derived EVs regulated the survival and function of human pancreatic β cells and pancreatic islets ( 164 ). For the role of EVs in islet transplantation, readers are encouraged to refer to the prior review ( 165 ).…”