Exosomal Secretion of Adipose Tissue during Various Physiological States

Abstract

Exosomes are secreted extracellular vesicles containing a wide array of biologically active components. Recent studies have demonstrated that exosomes serve as an important vehicle for extracellular communication and exert systemic effects on the physiology of organisms. Adipose tissues (ATs) play a key role in balancing systemic energy homeostasis as a central hub for fatty acid metabolism. At the same time, proper endocrine function of ATs has also been shown to be crucial for regulating physiological and metabolic health. The endocrine function of ATs is partially mediated by AT-derived exosomes that regulate metabolic homeostasis, such as insulin signaling, lipolysis, and inflammation. During the pathogenesis of obesity, metabolic syndrome, and cancer, exosomes shed by the resident cells in ATs may also have a role in regulating the progression of these diseases along with associated pathologies. In this review, we summarize the contents of AT-derived exosomes and their effects on various cell populations along with possible underlying molecular mechanisms. We further discuss the potential applications of exosomes as a drug delivery tool and therapeutic target.

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Abbreviations

ADSC:

Adipose-derived stem cells

AKT:

Protein kinase B

AM:

Adrenomedullin

AMPK:

AMP-activated protein kinase

APAF:

Apoptotic protease activating factor

AT:

Adipose tissue

AT-exos:

Adipose tissue derived exosomes

ARG:

Arginase

BAT:

Brown adipose tissue

BCAA:

Branched-chain amino acid transaminase, FABP, fatty acid binding protein

CCL:

Chemokine (C-C motif) ligand

CEBP:

CCAAT/ enhancer-binding protein

DLL:

Delta like canonical Notch ligand

ERK:

Extracellular signal regulated kinase

EVs:

Extracellular vesicles

FBXW7:

F-Box and WD repeat domain containing

FGF:

Fibroblast growth factor

FNDC:

Fibronectin type III domain-containing protein

GDM:

Gestational diabetes mellitus, aP, adipocyte protein

GLUT:

Glucose transporter

HSL:

Hormone sensitive lipase

HUVEC:

Human umbilical vein endothelial cells

IGFR:

Insulin-like growth factor receptor

IL:

Interleukin

IRS:

Insulin receptor substrate

KLF:

Kruppel-like factor

MALAT:

Metastasis associated lung adenocarcinoma transcript

MAPK:

Mitogen-activated protein kinase

MDM:

Mouse double minute homolog

MMP:

Matrix metalloproteinase

mTOR:

Mammalian target of rapamycin

NAFLD:

Nonalcoholic fatty liver disease, Bcl, B cell lymphoma

ob:

Leptin

PI3K:

Phosphoinositide 3-kinase

POMC:

Pro-opiomelanocortin

PPAR:

Peroxisome proliferator-activated receptor

PRDM:

PR domain containing

Ptch:

Patched-1 protein

PUM:

Pumilio RNA binding family member

RNCR3:

Retinal noncoding RNA3

SDF:

Stromal cell derived factor

SHH:

Sonic hedgehog

SIRT:

Sirtuin

STAT:

Signal transducer and activator of transcription

TGF:

Transforming growth factor

TIMP:

Tissue inhibitor of metalloproteinases

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

UCP:

Uncoupling protein

VEGF:

Vascular endothelial growth factor

WAT:

White adipose tissue

WISP:

WNT1 inducible signaling pathway protein, HIF, hypoxia induced factor

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was partially supported by grants from the National Cancer Institute of US National Institutes of Health (R01CA212609), and Purdue University Center for Cancer Research (P30CA023168).

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Quan, M., Kuang, S. Exosomal Secretion of Adipose Tissue during Various Physiological States. Pharm Res 37, 221 (2020). https://doi.org/10.1007/s11095-020-02941-6

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Key Words

  • adipocyte
  • extracellular vesicles
  • obesity
  • metabolism
  • drug delivery