High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance

Kumar, Anil; Sundaram, Kumaran; Mu, Jingbo; Dryden, Gerald W.; Sriwastva, Mukesh K.; Lei, Chao; Zhang, Lifeng; Qiu, Xiaolan; Xu, Fangyi; Yan, Jun; Zhang, Xiang; Park, Juw Won; Merchant, Michael L.; Bohler, Henry; Wang, Baomei; Zhang, Shuangqin; Qin, Chao; Xu, Ziying; Han, Xianlin; McClain, Craig J.; Teng, Yuee; Zhang, Huang‐Ge

doi:10.1038/s41467-020-20500-w

Cited by 153 publications

(137 citation statements)

References 76 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…Furthermore, this protective effect of BAT-derived exosomes might be related to exosomal proteins involved in mitochondria functions (Zhou et al, 2020). In the experiment conducted by Kumar et al (2021), exosomes were isolated from the feces of obese mice fed with a high-fat diet. These exosomes were given to lean mice, which then exhibited resistance to insulin.…”

Section: Milk-derived Evs and Metabolic Regulationmentioning

confidence: 99%

Biological Properties of Milk-Derived Extracellular Vesicles and Their Physiological Functions in Infant

Jiang

You

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are released by all cells under pathological and physiological conditions. EVs harbor various biomolecules, including protein, lipid, non-coding RNA, messenger RNA, and DNA. In 2007, mRNA and microRNA (miRNA) carried by EVs were found to have regulatory functions in recipient cells. The biological function of EVs has since then increasingly drawn interest. Breast milk, as the most important nutritional source for infants, contains EVs in large quantities. An increasing number of studies have provided the basis for the hypothesis associated with information transmission between mothers and infants via breast milk-derived EVs. Most studies on milk-derived EVs currently focus on miRNAs. Milk-derived EVs contain diverse miRNAs, which remain stable both in vivo and in vitro; as such, they can be absorbed across different species. Further studies have confirmed that miRNAs derived from milk-derived EVs can resist the acidic environment and enzymatic hydrolysis of the digestive tract; moreover, they can be absorbed by intestinal cells in infants to perform physiological functions. miRNAs derived from milk EVs have been reported in the maturation of immune cells, regulation of immune response, formation of neuronal synapses, and development of metabolic diseases such as obesity and diabetes. This article reviews current status and advances in milk-derived EVs, including their history, biogenesis, molecular contents, and biological functions. The effects of milk-derived EVs on growth and development in both infants and adults were emphasized. Finally, the potential application and future challenges of milk-derived EVs were discussed, providing comprehensive understanding and new insight into milk-derived EVs.

show abstract

Section: Milk-derived Evs and Metabolic Regulationmentioning

confidence: 99%

Biological Properties of Milk-Derived Extracellular Vesicles and Their Physiological Functions in Infant

Jiang

You

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Some of these exosomes seem to regulate insulin sensitivity through two different mechanisms: (i) indirectly by modulating inflammation, or (ii) by direct interaction with insulin-responsive organs. Both mechanisms affect insulin sensitivity through interaction with signaling and downstream molecules, such as phosphatidylinositol-3-kinase (PI3K)/Akt, IRS1, and glucose transporter 4 (GLUT-4), or by mediating the activation of inflammation [44,45]. The defective insulin signaling leads to a lower activity of endothelial nitric oxide synthase (eNOS), with a subsequent lower generation of nitric oxide (NO).…”

Section: Extracellular Vesicles and Insulin Signalingmentioning

confidence: 99%

“…Additionally, some of them are capable of binding to various proteins, including lipoproteins, or argonaute proteins, in order to form silencing complexes and alter the intracellular pathway of insulin signaling [48]. Consequently, some of these miRNAs have been described to regulate the expression of hepatic genes such as IRS1 and the peroxisome proliferator-activated receptor gamma (PPAR-γ) or interfere with important targets such as AKT-interacting protein (AKTIP) in skeletal muscle cells, among others [45,48].…”

Section: Extracellular Vesicles and Insulin Signalingmentioning

confidence: 99%

Organ Crosstalk and the Modulation of Insulin Signaling

Romero

Eckel

2021

Cells

View full text Add to dashboard Cite

A highly complex network of organ communication plays a key role in regulating metabolic homeostasis, specifically due to the modulation of the insulin signaling machinery. As a paradigm, the role of adipose tissue in organ crosstalk has been extensively investigated, but tissues such as muscles and the liver are equally important players in this scenario. Perturbation of organ crosstalk is a hallmark of insulin resistance, emphasizing the importance of crosstalk molecules in the modulation of insulin signaling, potentially leading to defects in insulin action. Classically secreted proteins are major crosstalk molecules and are able to affect insulin signaling in both directions. In this review, we aim to focus on some crosstalk mediators with an impact on the early steps of insulin signaling. In addition, we also summarize the current knowledge on the role of extracellular vesicles in relation to insulin signaling, a more recently discovered additional component of organ crosstalk. Finally, an attempt will be made to identify inter-connections between these two pathways of organ crosstalk and the potential impact on the insulin signaling network.

show abstract

“… 221 Also, it has recently been shown that intestinal exosomes released from high‐fat diet fed mice or T2D patients can induce insulin resistance in normal mice. 222 Pancreatic β‐cells, when exposed to increased fatty acid levels both in vitro and in vivo in mice, have been shown to release exosomes packed with miR‐29, which is involved in antagonizing insulin signaling in liver. 223 Additionally, INS1E β‐cells overexpressing human islet amyloid polypeptide (hIAPP) have been shown to secrete exosomes packed with hIAPP as a detoxification process, but the released hIAPP loaded exosomes can lead to neurodegenerative diseases.…”

Section: Nsmase2 Biochemistry and Regulationmentioning

confidence: 99%

Neutral sphingomyelinase‐2 and cardiometabolic diseases

et al. 2021

View full text Add to dashboard Cite

Sphingolipids, in particular ceramides, play vital role in pathophysiological processes linked to metabolic syndrome, with implications in the development of insulin resistance, pancreatic ß-cell dysfunction, type 2 diabetes, atherosclerosis, inflammation, nonalcoholic steatohepatitis, and cancer. Ceramides are produced by the hydrolysis of sphingomyelin, catalyzed by different sphingomyelinases, including neutral sphingomyelinase 2 (nSMase2), whose dysregulation appears to underlie many of the inflammation-related pathologies. In this review, we discuss the current knowledge on the biochemistry of nSMase2 and ceramide production and its regulation by inflammatory cytokines, with particular reference to cardiometabolic diseases. nSMase2 contribution to pathogenic processes appears to involve cyclical feedforward interaction with proinflammatory cytokines, such as TNF-α and IL-1ß, which activate nSMase2 and the production of ceramides, that in turn triggers the synthesis and release of inflammatory cytokines. We elaborate these pathogenic interactions at the molecular level and discuss the potential therapeutic benefits of inhibiting nSMase2 against inflammation-driven cardiometabolic diseases.

show abstract

High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance

Cited by 153 publications

References 76 publications

Biological Properties of Milk-Derived Extracellular Vesicles and Their Physiological Functions in Infant

Biological Properties of Milk-Derived Extracellular Vesicles and Their Physiological Functions in Infant

Organ Crosstalk and the Modulation of Insulin Signaling

Neutral sphingomyelinase‐2 and cardiometabolic diseases

Contact Info

Product

Resources

About