Exosomal miR‐122 promotes adipogenesis and aggravates obesity through the VDR/SREBF1 axis

Huang, Xiao‐Yan; Chen, Ji‐Xiong; Ren, Yi; Fan, Li‐Chun; Xiang, Wei

doi:10.1002/oby.23365

Cited by 27 publications

(21 citation statements)

References 38 publications

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“…Remarkably, miR-122 and miR-192 are strongly associated with cardiometabolic diseases—particularly T2D and MAFLD—in humans [ 53 , 54 , 55 ]. Recent data show that miR-122 promotes hepatic lipogenesis by targeting Sirt1 [ 56 ], whereas its inhibition in vitro in 3T3-L1 cells decreased Srebf1 [ 57 ]. We observed significantly increased Sirt1 and decreased Srebf1 in the liver and significantly increased Sirt1 and a tendency to decrease Srebf1 in the sWAT of EV mice—the two tissues that responded best to the EV-miRNAs treatment.…”

Section: Discussionmentioning

confidence: 99%

Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice

Castaño

Meza‐Ramos

Batlle

et al. 2022

IJMS

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Most cells release extracellular vesicles (EVs) that can be detected circulating in blood. We and others have shown that the microRNA contents of these vesicles induce transcriptomic changes in acceptor cells, contributing to the adjustment of metabolic homeostasis in response to environmental demands. Here, we explore the potential for modulating obesity- and exercise-derived EV-microRNAs to treat the metabolic dysfunction associated with obesity in mice. Treatment with EV-miRNAs alleviated glucose intolerance and insulin resistance in obese mice to an extent similar to that of high-intensity interval training, although only exercise improved cardiorespiratory fitness and decreased body weight. Mechanistically, EV-miRNAs decreased fatty acid and cholesterol biosynthesis pathways in the liver, reducing hepatic steatosis and increasing insulin sensitivity, resulting in decreased glycemia and triglyceridemia. Our data suggest that manipulation of EV-miRNAs may be a viable strategy to alleviate metabolic dysfunction in obese and diabetic patients who are unable to exercise, although actual physical activity is needed to improve cardiorespiratory fitness.

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Section: Discussionmentioning

confidence: 99%

Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice

Castaño

Meza‐Ramos

Batlle

et al. 2022

IJMS

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“…Many other regulators also play a part during this process, including sterol regulatory element-binding transcription factor 1c (SREBF1c), STAT5, and delta-like 1 (DLK1) [ 133 , 134 , 135 ]. In addition, there is evidence both in vivo and in vitro that VDR interacts with other regulators and influences the progression of adipogenesis, although these results are inconsistent [ 136 , 137 , 138 ].…”

Section: The Effects Of Maternal Vd Deficiency On Offspring Obesity A...mentioning

confidence: 99%

The Role of Maternal Vitamin D Deficiency in Offspring Obesity: A Narrative Review

Zeng

Zhang

et al. 2023

Nutrients

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Currently, vitamin D (VD) deficiency during pregnancy is widespread globally, causing unfavorable pregnancy outcomes for both mothers and infants for a longer time than expected, based on the Developmental Origins of Health and Disease (DOHaD) theory. As VD plays a key role in maintaining normal glucose and lipid metabolism, maternal VD deficiency may lead to obesity and other obesity-related diseases among offspring later in life. This review mainly focuses on the effect of maternal VD deficiency on offspring lipid metabolism, reviewing previous clinical and animal studies to determine the effects of maternal VD deficit on offspring obesity and potential mechanisms involved in the progression of offspring obesity. Emerging clinical evidence shows that a low VD level may lead to abnormal growth (either growth restriction or largeness for gestational age) and lipid and glucose metabolism disorders in offspring. Here, we also outline the link between maternal VD deficiency and life-long offspring effects, including the disorder of adipogenesis, the secretion of adipocytokines (including leptin, resistin, and adiponectin), activated systemic inflammation, increased oxidative reactions in adipose tissue, insulin resistance, and abnormal intestinal gut microbiota. Thus, there is an urgent need to take active steps to address maternal VD deficiency to relieve the global burden of obesity.

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“…Compare with control cells, high levels of miR-122 were found only in adipose tissue-derived exosomes (EXs-AT) and EXs-AT-treated cells. Overexpression of miR-122 promoted adipogenesis, while miR-122 inhibition prevented adipogenesis by regulating VDR, SREBF1, PPAR-γ, LPL and adiponectin ( 57 ). Our previous results in vitro study also showed that overexpressed miR-130b could be successfully packaged into EXs, and EXs-miR-130b could be taken up into porcine subcutaneous preadipocytes and inhibited the adipogenic differentiation by inhibiting the expression of PPAR-γ and its related genes ( 49 ).…”

Section: Exs-derived Mirnas Regulate Adipogenic Differentiationmentioning

confidence: 99%

The emerging roles and mechanisms of exosomal non-coding RNAs in the mutual regulation between adipose tissue and other related tissues in obesity and metabolic diseases

et al. 2022

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Exosomes (EXs) are the major types of extracellular vesicles (EVs) of 30-100 nm diameter that can be secreted by most cells to the extracellular environment. EXs transport endogenous cargoes (proteins, lipids, RNAs, etc.) to target cells and thereby triggers the release of these bioactive components, which then play important roles in regulating numerous biological processes under both physiological and pathological conditions. Throughout the studies in recent years, growing evidences have shown that EXs-derived non-coding RNAs (EXs-ncRNAs) are emerging as key players in cell-to-cell communication between adipose tissue and other related tissues in obesity and metabolic diseases. In this review, we will summarize the recent findings about EXs-ncRNAs, especially focus on the following aspects: 1) the biogenesis of EXs and emerging roles of EXs-ncRNAs, 2) the role of EXs-ncRNAs (EXs-miRNAs, EXs-lncRNAs, EXs-circRNAs, etc.) that were secreted by adipose-related tissues in promoting the differentiation of preadipocytes into mature and fully functional adipocytes, and 3) the crosstalk between the adipose tissue derived EXs-ncRNAs and the development of insulin resistance, obesity and various cancers. This review aims to reveal the emerging roles and mechanisms of EXs-ncRNAs in the mutual regulation of adipose tissue and its related tissues in obesity and metabolic diseases, so as to provide references for elucidating the etiology of obesity and related metabolic diseases and screening novel therapeutic targets.

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Exosomal miR‐122 promotes adipogenesis and aggravates obesity through the VDR/SREBF1 axis

Cited by 27 publications

References 38 publications

Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice

Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice

The Role of Maternal Vitamin D Deficiency in Offspring Obesity: A Narrative Review

The emerging roles and mechanisms of exosomal non-coding RNAs in the mutual regulation between adipose tissue and other related tissues in obesity and metabolic diseases

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