Skeletal Muscle Cell Growth Alters the Lipid Composition of Extracellular Vesicles

Valentino, Taylor; Rule, Blake D; Mobley, C. Brooks; Nikolova‐Karakashian, Mariana; Vechetti, Ivan J.

doi:10.3390/membranes11080619

Cited by 8 publications

(5 citation statements)

References 80 publications

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“…Certain lipid kinds are enriched in exosomes compared to their parent cells, suggesting that some membrane reorganization occurs upon exosome biogenesis. 91 Lipid species enriched in exosomes include ceramides (Cer), sphingomyelins (SM), and gangliosides GM3 from the class of sphingolipids; phosphatidylserines (PS), phosphatidylethanolamines (PE), phosphatidylcholines (PC), lyso-phosphatidylcholines, and phosphatidylinositols (PI) from the class of phospholipids; diacylglycerols (DAG); as well as cholesterol (Figure 10). 92,93 The parental cell types and their physiological status are determinants of the proportion of the lipid content in exosomes.…”

Section: Characterization Of Exosomesmentioning

confidence: 99%

Exosomes─Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics

et al. 2022

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Exosomes are a subgroup of nanosized extracellular vesicles enclosed by a lipid bilayer membrane and secreted by most eukaryotic cells. They represent a route of intercellular communication and participate in a wide variety of physiological and pathological processes. The biological roles of exosomes rely on their bioactive cargos, including proteins, nucleic acids, and lipids, which are delivered to target cells. Their distinctive properties�innate stability, low immunogenicity, biocompatibility, and good biomembrane penetration capacity�allow them to function as superior natural nanocarriers for efficient drug delivery. Another notably favorable clinical application of exosomes is in diagnostics. They hold various biomolecules from host cells, which are indicative of pathophysiological conditions; therefore, they are considered vital for biomarker discovery in clinical diagnostics. Here, we use data from the CAS Content Collection and provide a landscape overview of the current state and delineate trends in research advancement on exosome applications in therapeutics and diagnostics across time, geography, composition, cargo loading, and development pipelines. We discuss exosome composition and pathway, from their biogenesis and secretion from host cells to recipient cell uptake. We assess methods for exosome isolation and purification, their clinical applications in therapy and diagnostics, their development pipelines, the exploration goals of the companies, the assortment of diseases they aim to treat, development stages of their research, and publication trends. We hope this review will be useful for understanding the current knowledge in the field of medical applications of exosomes, in an effort to further solve the remaining challenges in fulfilling their potential.

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Section: Characterization Of Exosomesmentioning

confidence: 99%

Exosomes─Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics

et al. 2022

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“…A dose of 200 ng/ml IGF1 was chosen based on Valentino et al. ( 2021 ) who used a similar dose to stimulate hypertrophy of C2C12 myotubes. A dose of 1 mM AICAR was chosen based on its common usage in stimulating AMPK activity (Hinkle et al., 2022 ; Sato et al., 2014 ; Tong et al., 2009 ).…”

Section: Methodsmentioning

confidence: 99%

Proteolytic markers associated with a gain and loss of leg muscle mass with resistance training followed by high‐intensity interval training

Michel,

Godwin,

Plotkin

et al. 2023

Experimental Physiology

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We recently reported that vastus lateralis (VL) cross‐sectional area (CSA) increases after 7 weeks of resistance training (RT, 2 days/week), with declines occurring following 7 weeks of subsequent treadmill high‐intensity interval training (HIIT) (3 days/week). Herein, we examined the effects of this training paradigm on skeletal muscle proteolytic markers. VL biopsies were obtained from 11 untrained college‐aged males at baseline (PRE), after 7 weeks of RT (MID), and after 7 weeks of HIIT (POST). Tissues were analysed for proteolysis markers, and in vitro experiments were performed to provide additional insights. Atrogene mRNAs (TRIM63, FBXO32, FOXO3A) were upregulated at POST versus both PRE and MID (P < 0.05). 20S proteasome core protein abundance increased at POST versus PRE (P = 0.031) and MID (P = 0.049). 20S proteasome activity, and protein levels for calpain‐2 and Beclin‐1 increased at MID and POST versus PRE (P < 0.05). Ubiquitinated proteins showed model significance (P = 0.019) with non‐significant increases at MID and POST (P > 0.05). in vitro experiments recapitulated the training phenotype when stimulated with a hypertrophic stimulus (insulin‐like growth factor 1; IGF1) followed by a subsequent AMP‐activated protein kinase activator (5‐aminoimidazole‐4‐carboxamide ribonucleotide; AICAR), as demonstrated by larger myotube diameter in IGF1‐treated cells versus IGF1 followed by AICAR treatments (I+A; P = 0.017). Muscle protein synthesis (MPS) levels were also greater in IGF1‐treated versus I+A myotubes (P < 0.001). In summary, the loss in RT‐induced VL CSA with HIIT coincided with increases in several proteolytic markers, and sustained proteolysis may have driven this response. Moreover, while not measured in humans, we interpret our in vitro data to suggest that (unlike RT) HIIT does not stimulate MPS.New Findings What is the central question of this study? Determining if HIIT‐induced reductions in muscle hypertrophy following a period of resistance training coincided with increases in proteolytic markers. What is the main finding and its importance? Several proteolytic markers were elevated during the HIIT training period implying that increases in muscle proteolysis may have played a role in HIIT‐induced reductions in muscle hypertrophy.

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“…For example, under hypertrophic conditions, exosomes derived from C2C12 skeletal muscle cells can induce lipolysis in adipose tissue. In addition, they observed a significant increase in ceramide species (C16, C18:1, C24:0 and C24:1) and diacylglycerol containing unsaturated fatty acids, such as palmitoyl-arachidonoyl, but a reduction in C20 and C22 species (Valentino et al, 2021). Exosomes can affect lipid metabolism in adipose tissue since they can transport enzymes, such as phospholipases A2, cytosolic phospholipases A2, calcium-independent phospholipases A2, phospholipase D2, diglyceride kinase, phosphoinositide phosphatase related to lipid metabolism (Record et al, 2014).…”

Section: Lipid Metabolism Involvement and Extracellular Vesicle Lipid...mentioning

confidence: 97%

The lipid composition of extracellular vesicles: applications in diagnostics and therapeutic delivery

Ghadami¹,

Dellinger²

2023

Front. Mol. Biosci.

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Extracellular vesicles (EVs), including exosomes, with nanoscale sizes, biological origins, various functions, and unique lipid and protein compositions have been introduced as versatile tools for diagnostic and therapeutic medical applications. Numerous studies have reported the importance of the lipid composition of EVs and its influence on their mechanism of action. For example, changes in the lipidomic profile of EVs have been shown to influence the progression of various diseases, including ovarian malignancies and prostate cancer. In this review, we endeavored to examine differences in the lipid content of EV membranes derived from different cell types to characterize their capabilities as diagnostic tools and treatments for diseases like cancer and Alzheimer’s disease. We additionally discuss designing functionalized vesicles, whether synthetically by hybrid methods or by changing the lipid composition of natural EVs. Lastly, we provide an overview of current and potential biomedical applications and perspectives on the future of this growing field.

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Skeletal Muscle Cell Growth Alters the Lipid Composition of Extracellular Vesicles

Cited by 8 publications

References 80 publications

Exosomes─Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics

Exosomes─Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics

Proteolytic markers associated with a gain and loss of leg muscle mass with resistance training followed by high‐intensity interval training

The lipid composition of extracellular vesicles: applications in diagnostics and therapeutic delivery

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