# The interplay between exosomal miRNAs and cytokine networks in metabolic diseases

**Authors:** Radhika Joshi, Kanika Verma, Devesh U. Kapoor, Vipin Saini, Swapnil Sharma

PMC · DOI: 10.3389/fcell.2026.1731121 · Frontiers in Cell and Developmental Biology · 2026-02-19

## TL;DR

This paper reviews how exosomal miRNAs regulate metabolism and interact with cytokines, offering potential for diagnosing and treating metabolic diseases like diabetes and obesity.

## Contribution

The paper provides a comprehensive review of the mechanistic roles and therapeutic potential of exosomal miRNAs in metabolic diseases.

## Key findings

- Exosomal miRNAs modulate insulin signaling, lipid catabolism, and inflammation in metabolic diseases.
- Specific miRNAs like miR-122, miR-155, and miR-34a are linked to obesity, diabetes, and NAFLD.
- Advances in exosome engineering and high-throughput profiling enhance their therapeutic and diagnostic potential.

## Abstract

Exosomal microRNAs (miRNAs) are increasingly recognized as central regulators of metabolic pathways, influencing glucose homeostasis, lipid metabolism, and inflammatory responses. Their ability to mediate inter-organ communication positions them as both biomarkers and therapeutic candidates for metabolic diseases such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD). This review synthesizes recent literature on the mechanistic roles of exosomal miRNAs in metabolic regulation, their influence on insulin sensitivity and lipid homeostasis, and their interaction with cytokine networks. It also evaluates current approaches in exosome engineering, including miRNA enrichment, surface modification, and CRISPR/Cas9-based editing, as well as emerging high-throughput technologies for profiling exosomal miRNAs. Exosomal miRNAs modulate insulin signaling, lipid catabolism, adipogenesis, and inflammatory responses, thereby contributing to metabolic adaptation and disease progression. Specific miRNAs, such as miR-122, miR-155, and miR-34a, have been implicated in obesity, diabetes, and NAFLD, serving as both biomarkers and therapeutic targets. Advances in exosome engineering and delivery strategies have demonstrated improved specificity, stability, and therapeutic efficacy. High-throughput sequencing and single-vesicle analyses provide insights into the heterogeneity and dynamics of exosomal miRNAs, supporting their clinical translation. Exosomal miRNAs represent promising tools for diagnosis and therapy in metabolic disorders. Their dual role as regulators of metabolic processes and carriers of therapeutic cargo underscores their potential in precision medicine. Future integration of bioengineering, CRISPR-based modulation, and omics-driven predictive modeling will enhance their translational applicability, paving the way for personalized therapies in metabolic diseases.

Flowchart-style illustration showing exosome structure, exosome callout, and exosome microRNA, connecting to metabolic diseases in a human body diagram. Text boxes note exosomes as nanosized vesicles, containing proteins, lipids, nucleic acids, and acting as transport vehicles in cellular communication. Exosomal microRNAs are linked with metabolic diseases including obesity, NAFLD, and diabetes.

## Linked entities

- **Diseases:** type 2 diabetes (MONDO:0005148), obesity (MONDO:0011122), non-alcoholic fatty liver disease (MONDO:0013209), NAFLD (MONDO:0013209), diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, Mir16-1 (microRNA 16-1) [NCBI Gene 387134] {aka Mirn16, Mirn16-1, miR-16, mir-16-1}, Cd63 (CD63 antigen) [NCBI Gene 12512] {aka ME491, Tspan30}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Irak1 (interleukin-1 receptor-associated kinase 1) [NCBI Gene 16179] {aka IRAK, IRAK-1, IRAK1-S, IRAK1b, Il1rak, Plpk}, Fdft1 (farnesyl diphosphate farnesyl transferase 1) [NCBI Gene 14137] {aka SQS, SS}, Pten (phosphatase and tensin homolog) [NCBI Gene 19211] {aka 2310035O07Rik, A130070J02Rik, B430203M17Rik, MMAC1, PTENbeta, TEP1}, Vdac1 (voltage-dependent anion channel 1) [NCBI Gene 22333] {aka Vdac5, mVDAC1, mVDAC5}, Mir155 (microRNA 155) [NCBI Gene 387173] {aka Mirn155, mir-155, mmu-mir-155}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, MIR378E (microRNA 378e) [NCBI Gene 100616498] {aka mir-378e}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, G6pc3 (glucose 6 phosphatase, catalytic, 3) [NCBI Gene 68401] {aka 0710001K01Rik, UGRP}, Pkm (pyruvate kinase, muscle) [NCBI Gene 18746] {aka Pk-2, Pk-3, Pk3, Pkm2}, Mir223 (microRNA 223) [NCBI Gene 723814] {aka Mirn223, miR-223, mmu-mir-223}, Mir99a (microRNA 99a) [NCBI Gene 387229] {aka Mirn99a, mir-99a, mmu-mir-99a}, Mir15b (microRNA 15b) [NCBI Gene 387175] {aka Mirn15b, mir-15b, mmu-mir-15b}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, Traf6 (TNF receptor-associated factor 6) [NCBI Gene 22034] {aka 2310003F17Rik, C630032O20Rik}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, Socs1 (suppressor of cytokine signaling 1) [NCBI Gene 12703] {aka Cish1, Cish7, JAB, SOCS-1, SSI-1}, MIR5703 (microRNA 5703) [NCBI Gene 100847081] {aka mir-5703}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, Cd81 (CD81 antigen) [NCBI Gene 12520] {aka Tapa-1, Tapa1, Tspan28}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Slc2a4 (solute carrier family 2 (facilitated glucose transporter), member 4) [NCBI Gene 20528] {aka GT2, Glut-4, Glut4, twgy}, Fabp4 (fatty acid binding protein 4, adipocyte) [NCBI Gene 11770] {aka 422/aP2, AFABP, ALBP, ALBP/Ap2, Ap2, Lbpl}, Mir20b (microRNA 20b) [NCBI Gene 723923] {aka Mirn20b, mir-20b, mmu-mir-20b}, Mir146b (microRNA 146b) [NCBI Gene 751550] {aka Mirn146b, mir-146b}, Mir192 (microRNA 192) [NCBI Gene 387187] {aka Mirn192, mir-192, mmu-mir-192}, Mafb (MAF bZIP transcription factor B) [NCBI Gene 16658] {aka Kreisler, Krml, Krml1, kr}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Irs1 (insulin receptor substrate 1) [NCBI Gene 16367] {aka G972R, IRS-1}, Mir1955 (microRNA 1955) [NCBI Gene 100316756] {aka mir-1955, mmu-mir-1955}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Ptch1 (patched 1) [NCBI Gene 19206] {aka A230106A15Rik, Ptc, Ptc1, Ptch, mes, wig}, Mir146 (microRNA 146) [NCBI Gene 387164] {aka Mirn146, miR-146a, mmu-mir-146}, Acaca (acetyl-Coenzyme A carboxylase alpha) [NCBI Gene 107476] {aka A530025K05Rik, Acac, Acc1, Gm738}, Gys1 (glycogen synthase 1, muscle) [NCBI Gene 14936] {aka Gys3, MGS}, Mir144 (microRNA 144) [NCBI Gene 387162] {aka Mirn144, mir-144, mmu-mir-144}, Mir206 (microRNA 206) [NCBI Gene 387202] {aka Mirn206, mmu-mir-206}, Cpt2 (carnitine palmitoyltransferase 2) [NCBI Gene 12896] {aka CPTII}, Mir143 (microRNA 143) [NCBI Gene 387161] {aka Mirn143, mir-143, mmu-mir-143}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Mir451a (microRNA 451a) [NCBI Gene 723870] {aka Mir451, Mirn451, mir-451a, mmu-mir-451, mmu-mir-451a}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Sdcbp (syndecan binding protein) [NCBI Gene 53378] {aka MDA-9, Sycl, syntenin-1}, MIR122 (microRNA 122) [NCBI Gene 406906] {aka MIR122A, MIRN122, MIRN122A, hsa-mir-122, miRNA122, miRNA122A}, Mir210 (microRNA 210) [NCBI Gene 387206] {aka Mirn210, mir-210, mmu-mir-210}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Mir27a (microRNA 27a) [NCBI Gene 387220] {aka Mirn27a, mir-27a, mmu-mir-27a}, Rnls (renalase, FAD-dependent amine oxidase) [NCBI Gene 67795] {aka 6530404N21Rik, C10orf59}, Mir34a (microRNA 34a) [NCBI Gene 723848] {aka Mirn34a, mir-34a, mmu-mir-34a}, Mir205 (microRNA 205) [NCBI Gene 387201] {aka Mirn205, mir-205, mmu-mir-205}, GYS1 (glycogen synthase 1) [NCBI Gene 2997] {aka GSY, GYS}
- **Diseases:** mitochondrial dysfunction (MESH:D028361), dyslipidemia (MESH:D050171), metabolic syndrome (MESH:D024821), hyperglycemia (MESH:D006943), adipose inflammation (MESH:D007249), diseases of the liver (MESH:D008107), impaired glucose metabolism (MESH:D044882), impaired glucose transport (MESH:C536830), prediabetes (MESH:D011236), Diabetes mellitus (MESH:D003920), cancerous (MESH:D009369), NAFLD (MESH:D065626), myocarditis (MESH:D009205), GDM (MESH:D016640), autoimmune (MESH:D001327), NASH (MESH:D005235), Obese (MESH:D009765), hepatic steatosis (MESH:D005234), metabolic dysregulation (MESH:D021081), metabolic (MESH:D008659), Rare metabolic disorders (MESH:D035583), insulin (MESH:D007333), toxicity (MESH:D064420), hypertrophy (MESH:D006984), cardiovascular diseases (MESH:D002318), T1DM (MESH:D003922), liver damage (MESH:D056486), TIID (MESH:D003924), glucose intolerance (MESH:D018149)
- **Chemicals:** phosphate (MESH:D010710), fat (MESH:D005223), Oil Red O (MESH:C011049), glycogen (MESH:D006003), Cholesterol (MESH:D002784), glycolipid (MESH:D006017), biotin (MESH:D001710), CaCl2 (MESH:D002122), HG (MESH:D008628), AK083884 (-), fatty acid (MESH:D005227), TCA (MESH:D014238), pioglitazone (MESH:D000077205), LPS (MESH:D008070), lipid (MESH:D008055), steroid (MESH:D013256), ATP (MESH:D000255), Glucose (MESH:D005947), hydrogen (MESH:D006859)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HUVEC — Homo sapiens (Human), Finite cell line (CVCL_2959), 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), Mki67 — Mus musculus (Mouse), Hybridoma (CVCL_B7D2)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960101/full.md

## References

153 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960101/full.md

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Source: https://tomesphere.com/paper/PMC12960101