Hepatocytes derived extracellular vesicles from high-fat diet induced obese mice modulate genes expression and proliferation of islet β cells

Fu, Qi; Li, Yue; Jiang, Hemin; Zheng, Shen; Gao, Rui; He, Yunqiang; Liu, Yuwei; Xu, Kuanfeng; Yang, Tao

doi:10.1016/j.bbrc.2019.06.124

Cited by 31 publications

(27 citation statements)

References 19 publications

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“…In order to verify our previous microarray results ( 23 ), the expression levels of miR-129-5p, miR-135a-3p and miR-504-3p was measured in hepatocellular EVs using RT-qPCR. The results showed that all three miRNAs exhibited lower expression levels in hepatocellular EVs from mice fed HFD compared with in mice fed CD, showing consistency with our previous microarray results ( Fig.…”

Section: Resultsmentioning

confidence: 81%

“…miR-129-5p, miR-135a-3p and miR-504-3p expression levels decrease in serum EVs in mice fed HFD. According to our previous study (23), C57BL/6J mice were fed HFD for 12 weeks for induction of an NAFLD model. EVs were collected from the culture medium of hepatocytes from mice fed HFD or CD.…”

Section: Isolation and Characterization Of Hepatocyte-released Evsmentioning

confidence: 99%

“…Our previous study identified dysregulated miRNA expression levels in EVs secreted by hepatic cells in mice fed high-fat diet (HFD) compared with mice fed chow diet (CD) using microarray analysis ( 23 ). It is still not known whether liver EV-derived miRNAs can be used to discriminate between patients with NAFLD and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Circulating microRNA‑135a‑3p in serum extracellular vesicles as a potential biological marker of non‑alcoholic fatty liver disease

Jiang

Zheng

et al. 2021

Mol Med Rep

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Non-alcoholic fatty liver disease (NAFLD) is a widespread threat to human health. However, the present screening methods for NAFLD are time-consuming or invasive. The present study aimed to assess the potential of microRNAs (miRNAs/miRs) in serum extracellular vesicles (EVs) as a biomarker of NAFLD. C57BL/6J mice were fed either a 12-week high-fat diet (HFD) or standard chow to establish NAFLD and control groups, respectively. Serum samples were obtained from the mouse model of NAFLD, as well as 50 patients with NAFLD and 50 healthy individuals, and EVs were extracted and verified. Using reverse transcription-quantitative PCR, the mRNA expression level of selected miRNAs in the serum and EVs was analyzed. In order to determine the diagnostic value, receiver operating characteristic (ROC) curves were used. The mice treated with HFD showed notable hepatic steatosis and higher concentrations of serum alanine aminotransferase (ALT). There was also a significant decrease in the expression levels of miR-135a-3p, miR-129b-5p and miR-504-3p, and an increase in miR-122-5p expression levels in circulating EVs in mice treated with HFD and patients with NAFLD. There were also similar miR-135a-3p and miR-122-5p expression patterns in the serum. ROC analysis demonstrated that miR-135a-3p in circulating EVs was highly accurate in diagnosing NAFLD, with the area under the curve value being 0.849 (95% CI, 0.777-0.921; P<0.0001). Bioinformatics analysis indicated that dysregulated miR-135a-3p was associated with 'platelet-derived growth factor receptor signaling pathway' and 'AMP-activated protein kinase signaling pathway'. In summary, circulating miR-135a-3p in EVs may serve as a potential non-invasive biomarker to diagnose NAFLD. This miRNA was a more sensitive and specific biological marker for NAFLD compared with ALT.

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Section: Resultsmentioning

confidence: 81%

Section: Isolation and Characterization Of Hepatocyte-released Evsmentioning

confidence: 99%

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Circulating microRNA‑135a‑3p in serum extracellular vesicles as a potential biological marker of non‑alcoholic fatty liver disease

Jiang

Zheng

et al. 2021

Mol Med Rep

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“…Within the context of both T1DM and T2DM, cells and tissues of origin for this EV crosstalk included β-cells and other islet cells (24)(25)(26)(27)(28)(29)(30)(31), immune cells (32-37), mesenchymal stem cells (38)(39)(40)(41)(42)(43), bone marrow (44,45), and vascular endothelium (46,47). In T2DM, skeletal muscle (48), liver (49), and adipose cells (50) also secrete EVs that affect β-cells. Additionally, serum-derived EVs of unknown cellular origin affect insulin secretion dynamics in T1DM, T2DM, and GDM pancreatic islets (51)(52)(53)(54).…”

Section: Ev Crosstalk Dynamicsmentioning

confidence: 99%

The Role of Extracellular Vesicles in β-Cell Function and Viability: A Scoping Review

et al. 2020

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Extracellular vesicles (EVs) released by cells throughout the body have been implicated in diabetes pathogenesis. Understanding the role of EVs in regulation of β-cell function and viability may provide insights into diabetes etiology and may lead to the development of more effective screening and diagnostic tools to detect diabetes earlier and prevent disease progression. This review was conducted to determine what is known from the literature about the effect of EV crosstalk on pancreatic β-cell function and viability in the pathogenesis of diabetes mellitus, to perform a gap analysis for future research directions, and to discuss implications of available evidence for diabetes care. The literature search yielded 380 studies from which 31 studies were determined to meet eligibility criteria. The majority of studies had the disease context of autoimmunity in T1DM. The most commonly studied EV crosstalk dynamics involved localized EV-mediated communication between β-cells and other islet cells, or between β-cells and immune cells. Other organs and tissues secreting EVs that affect β-cells include skeletal muscle, hepatocytes, adipocytes, immune cells, bone marrow, vascular endothelium, and mesenchymal stem cells. Characterization of EV cargo molecules with regulatory effects in β-cells was conducted in 24 studies, with primary focus on microRNA cargo. Gaps identified included scarcity of evidence for the effect on β-cell function and viability of EVs from major metabolic organs/tissues such as muscle, liver, and adipose depots. Future research should address these gaps as well as characterize a broader range of EV cargo molecules and their activity in β-cells.

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“…Liver, an important organ participating in fat metabolism, glycogen synthesis and decomposition, may play a role in regulating pancreatic β -cells. We previously identified that hepatocytes derived extracellular vesicles from high-fat diet (HFD) induced obese mice could modulate genes expression and promote proliferation of islet β -cells through miRNA [14]. During the last decade, other liver-derived circulating factors such as hepatic growth factor (HGF) [15,16], leukocyte-neutrophil elastase inhibitor (SerpinB1) [17], kisspeptin [18] and fibroblast growth factor 21 (FGF21) [19] have been reported to directly affect islet secretion, proliferation and regeneration.…”

Section: Introductionmentioning

confidence: 99%

Temporal Metabolic Characteristics and Transcriptomic Landscape of Islets and Liver Reveal Dynamic Pathophysiology and Interorgan Crosstalk in High-fat Diet-induced Diabetes

Gao

Jiang

et al. 2020

Preprint

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ObjectiveHyperinsulinemia and insulin resistance are co-existing characteristics of type 2 diabetes, whereas the molecular mechanism underlying this deleterious cycle remains elusive. The temporal transcriptomic landscape of core organs responsible for insulin secretion (islets) and insulin action (liver) could provide new insights.MethodsThe longitudinal profiling of glucose metabolism, insulin sensitivity, islet architecture and secretion were conducted in C57BL/6N mice fed a high-fat diet (HFD) or chow diet for 24 weeks. RNA-sequencing of islets and liver were performed once every 4 weeks. Weighted gene co-expression network analysis and Ingenuity Pathway Analysis were applied to construct networks and evaluate co-ordinated molecular interactions between islets and liver.ResultsMice exhibited progressively deteriorated glucose homeostasis with hyperinsulinemia but impaired first-phase insulin secretion after 4 weeks on HFD. Insulin, glucagon and somatostatin secretion in response to glucose with or without palmitate gradually deteriorated from dysregulation to failure. Systemic insulin resistance developed over 24 weeks with variable time course in tissue-specific insulin action. Our transcriptomic datasets outlined the impact of HFD on dynamics of islet and liver molecular network at different stages. Correlation analyses revealed that both organs jointly programmed β-cell compensatory adaption via cell proliferation at early phase and irreversible islet dysfunction by inappropriate immune response at later stage. Alternations of T cell subpopulations validated the participation of adaptive immune response through priming and amplification phases in diabetic progression.ConclusionOur data provide a comprehensive landscape of crosstalk between islets and liver in diet-induced diabetes, elucidating the development of islet dysfunction and insulin resistance.HighlightsDiet-induced diabetes is featured by transition from islet dysfunction to failureInsulin resistance develops with variable time course in different tissuesDynamics of islet and liver molecular network interplay at different stagesCell proliferation and improper immune reaction mediated interorgan crosstalkAdaptive immune response participated via priming and amplification phases

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Hepatocytes derived extracellular vesicles from high-fat diet induced obese mice modulate genes expression and proliferation of islet β cells

Cited by 31 publications

References 19 publications

Circulating microRNA‑135a‑3p in serum extracellular vesicles as a potential biological marker of non‑alcoholic fatty liver disease

Circulating microRNA‑135a‑3p in serum extracellular vesicles as a potential biological marker of non‑alcoholic fatty liver disease

The Role of Extracellular Vesicles in β-Cell Function and Viability: A Scoping Review

Temporal Metabolic Characteristics and Transcriptomic Landscape of Islets and Liver Reveal Dynamic Pathophysiology and Interorgan Crosstalk in High-fat Diet-induced Diabetes

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