The extracellular vesicles (EVs) have emerged as key players in metabolic disorders rising as an alternative way of paracrine/endocrine communication. In particular, in relation to adipose tissue ...(AT) secreted EVs, the current knowledge about its composition and function is still very limited. Nevertheless, those vesicles have been lately suggested as key players in AT communication at local level, and also with other metabolic peripheral and central organs participating in physiological homoeostasis, and also contributing to the metabolic deregulation related to obesity, diabetes, and associated comorbidities. The aim of this review is to summarize the most relevant data around the EVs secreted by adipose tissue, and especially in the context of obesity, focusing in its protein cargo. The description of the most frequent proteins identified in EVs shed by AT and its components, including their changes under pathological status, will give the reader a whole picture about the membrane/antigens, and intracellular proteins known so far, in an attempt to elucidate functional roles, and also suggesting biomarkers and new paths of therapeutic action.
Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important ...contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague–Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.
Extracellular vesicles (EVs) have been recently postulated as key players in metabolic disorders emerging as an alternative way of paracrine/endocrine communication. However, the nature of EVs shed ...by adipose tissue (AT) and their role in obesity is still very limited. Here, we isolated human morbid obese visceral (VAT) and subcutaneous (SAT) whole AT shed EVs from donors submitted to bariatric surgery to characterize their protein cargo by qualitative and quantitative/SWATH mass spectrometry analysis. We identified 574 different proteins shed by morbid obese VAT and 401 proteins in those from SAT, establishing the first obese AT EV proteome reference map. Only 50% of identified proteins in VAT vesicles were common to those in SAT; additionally, EVs shed by obese VAT showed more AT and obesity-related adipokines than SAT. Functional classification shows that obese VAT vesicles exhibit an enrichment of proteins implicated in AT inflammation and insulin resistance such as TGFBI, CAVN1, CD14, mimecan, thrombospondin-1, FABP-4 or AHNAK. Selected candidate biomarkers from the quantitative-SWATH analysis were validated in EVs from independent morbid obese and from moderate obese to lean individuals showing that morbid obese VAT vesicles are characterized by a diminution of syntenin 1 and the elevation of TGFBI and mimecan. Interestingly, TGFBI and mimecan containing vesicles could be detected and quantified at circulating level in plasma. Thus, a significant elevation of -TGFBI-EVs was detected on those obese patients with a history of T2D compared to nondiabetic, and an augmentation of mimecan-EVs in obese plasma compared to those in healthy lean individuals. Thus, we conclude that obese AT release functional EVs carrying AT and obesity candidate biomarkers which vary regarding the AT of origin. Our findings suggest that circulating EV-TGFBI may facilitate monitoring T2D status in obese patients, and EV-mimecan may be useful to track adiposity, and more precisely, visceral obesity.
Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. ...However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.
Implant-based breast reconstructions (IBBRs) increased last years despite the growing indications for radiotherapy in the treatment of breast cancer. As a result, complications and reconstructive ...failures associated to IBBR have increased. Autologous breast reconstruction (ABR) using fat-augmented latissimus dorsi (FALD) has become popular in recent years.
We aimed to evaluate conversion to ABR using latissimus dorsi and immediate fat grafting in 61 cases with IBBR failure.
Immediate reconstruction was found significatively related with an increased number of surgeries resulting from IBBR complications (
< 0.001). Note that 41% of the cases presented a grade III/IV Baker and Palmer capsular contracture, 29% implant extrusion, and 21% implant infection. Mean survival of the first implant was 16.95 months. ABR process was completed in 47% of cases with a single surgery. Statistically significant differences were observed between this fact and previous IBBR failure due to infection (
= 0.03) or extrusion (
= 0.01). Mean volume of fat graft was 429.61 mL, mean length of the surgical procedure was 3.17 hours, and the average length of hospital stay after surgery was 2.67 days. Only 3.3% of the cases developed some major complication. None of the cases presented reconstructive failure.
FALD is a very safe total ABR technique, an important fact in patients with previous reconstructive failures. The large volume of fat that can be grafted in a single surgery allows the reconstruction of breast in a reasonable size. The reduced length of surgery and hospital stay make the FALD technique an option to consider when an autologous but efficient and safe reconstruction is desired.
Although autologous tissue reconstruction is the best option for breast reconstruction, using implants is still a reliable and simple method, offering acceptable aesthetic results. Becker-type ...implants are permanent implants that offer a 1-stage reconstructive option. A retrospective study was carried out in our center reviewing the clinical reports of 237 patients, in whom a total of 314 Becker-type prostheses were implanted. Overall survival was calculated using a Kaplan-Meier estimate. Cox proportional hazard models were used to calculate adjusted hazard ratios. At the end of the study, 214 expanders (68.15%) presented no complications, 40 (12.47%) developed significant capsular contracture, in 27 (8.60%) infection occurred, 24 (7.64%) suffered minor complications, and 9 (2.87%) ruptured. The mean survival time of the expanders was 120.41 months (95% CI: 109.62, 131.19). Radiotherapy, chemotherapy, high Molecular Immunology Borstel, age, mastectomy performed previously to the implant, ductal carcinoma, advanced tumoral stage, experience of the surgeon, and Becker 35-type implants were significantly related to a high number of complications in relation to the survival of the implants. Cox regression analysis revealed that the main risk factors for the survival of expander implants included radiotherapy and surgeon experience. The complication hazard ratio or relative risk caused by these 2 factors was 1.976 and 1.680, respectively. One-stage reconstruction using Becker-type expanders is an appropriate, simple, and reliable option in delayed breast reconstruction in patients who have not received radiotherapy and as long as the procedure is carried out by surgeons skilled in the technique.
To introduce a variant of the Furnas technique using a knotless bidirectional barbed absorbable suture for the correction of Weerda grade I prominent ears.
Comparative study between groups of ...patients and literature review.
Tertiary care teaching hospital.
Review of 25 patients who underwent otoplasty by the technique described by Furnas and 23 patients who underwent otoplasty by this modified technique using knotless bidirectional barbed absorbable sutures. Postoperative complications and level of satisfaction were measured.
The postoperative complication rate was low regardless of the suture technique used. We observed statistical significance in relation to the pain caused by the suture knots (P < .001). The reoperation rate was on the limit of statistical significance (P = .051). In the group with bidirectional barbed absorbable sutures, no reoperation was required. In the group with classic sutures, reoperation was necessary in 5 cases to correct recurrence and in 1 case to correct asymmetry. Furthermore, in 4 cases of this group, sutures were removed due to pain or extrusion. The overall long-term satisfaction rate was 91.6% in the group operated with classic suture techniques and 95.7% in the group operated with knotless bidirectional barbed absorbable sutures.
The use of knotless bidirectional barbed absorbable sutures in the Furnas technique is simple and fast and presents few complications. The major advantages that we obtained with the use of this technique were the absence of discomfort caused by the type of suture and the fact that no reoperation was required to correct relapses.
: We report the case of a 15‐year‐old boy with giant congenital melanocytic nevi on his back, buttocks, and rear of the two proximal thirds of his thighs, and neurocutaneous melanosis, diagnosed ...when he was 3 years old. Three melanocytic nodules were present in the giant nevi that were suspected to have malignant degeneration. A biopsy of these nodules was carried out, and histological study revealed benign proliferative melanocytic nodules within the giant congenital melanocytic nevi.
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