Re: Inflamed macrophage microvesicles induce insulin resistance in human adipocytes.

lawrence Hayes, Jameel Inal, Dan Stratton

Research output: Contribution to journalLetterpeer-review

45 Citations (Scopus)


To the editor, we read with interest the recent work of Zhang and colleagues [1] who explored insulin signalling and glucose uptake in human adipocytes from females of normal body mass index (BMI). Zhang et al. [1] characterized ‘microvesicles’ (MVs) shed by in vitro polarized THP-1 macrophages with M1 (pro-inflamatory) or M2 (anti-inflamatory) phenotypes and examined the influence of these MVs on adipocyte glucose uptake. We agree with the authors that extracellular vesicles may have profound influence on the crosstalk between macrophages and adipocytes. The general assumption that extracellular vesicles derived from inflamed macrophages play a role in reducing insulin signal transduction and decrease glucose uptake of human adipocytes by activation of nuclear factor (NF)-KB is also supported by available evidence within the article.

Whilst we found the aims and rationale to be of interest to the vesicle community, we suggest limitations with the author’s terminology and methodology, which limits satisfactory interpretation of results. Firstly, we take issue with the definition of MVs as ‘extracellular vesicles, microparticles, exosomes, or shedding vesicles’. Cellular stress indeed induces release of submicron MVs (0.1-1 um), in addition to exosomes (50-100 nm [2]), released through exocytosis. It is this primary characteristic of MVs (their established diameter [3]) that differentiates them from exosomes. It is evident the vesicles in Figure 2 [1] are less than 100 nm and therefore must be termed exosomes. Whilst this distinction may seem trivial, the mechanism of MV release (vesiculation) is regulated by different agents to exosomes [4], and the process by which MVs are shed from the cell membrane has distinct stages [2].

Typically MVs are isolated by ultracentrifugation of approximately 25,000 g for 90 min [5], however the centrifugation speeds indicated in Zhang et al. [1] are closer to the conditions necessary to isolate exosomes. Furthermore, we suggest a gentle sonication for 5 min in a sonicating water bath would increase MV purity by disaggregating clustered exosomes that have a similar mass to MVs and have often been isolated with MVs as ‘contaminating exosomes’ [6].

In conclusion, we believe the aforementioned factors coalesce to limit conclusions drawn. Indeed, exosomes have different biogenesis to MVs and exhibit distinct properties that should this studies results be built in to further study as suggested by the authors, could lead to confounding and misleading results.
Original languageEnglish
JournalNutrition and Metabolism
Publication statusPublished - 2015


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