scholarly journals Proteomic and Metabolomic Characterization of Metabolically Healthy Obesity: A Descriptive Study from a Swedish Cohort

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
J. Korduner ◽  
P. M. Nilsson ◽  
O. Melander ◽  
M. J. Gerl ◽  
G. Engström ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Principal Component ◽  
Metabolically Healthy Obesity ◽  
Established Risk Factor ◽  
The Metabolic Syndrome ◽  
Significant Difference ◽  
Metabolite Profiles ◽  
History Of ◽  
Metabolically Healthy

Background/Aims. Obesity is a well-established risk factor for the development of numerous chronic diseases. However, there is a small proportion of obese individuals that seem to escape these aforementioned conditions—Metabolically Healthy Obesity (MHO). Our aim was to do a metabolic and biomarker profiling of MHO individuals. Method. Associations between different biomarkers (proteomics, lipidomics, and metabolomics) coupled to either MHO or metabolically unhealthy obese (MUO) individuals were analyzed through principal component analysis (PCA). Subjects were identified from a subsample of 416 obese individuals, selected from the Malmö Diet and Cancer study—Cardiovascular arm (MDCS-CV, n = 3,443). They were further divided into MHO (n = 143) and MUO (n = 273) defined by a history of hospitalization, or not, at baseline inclusion, and nonobese subjects (NOC, n = 3,027). Two distinctive principle components (PL2, PP5) were discovered with a significant difference and thus further investigated through their main loadings. Results. MHO individuals had a more metabolically favorable lipid and glucose profile than MUO subjects, that is, lower levels of traditional blood glucose and triglycerides, as well as a trend of lower metabolically unfavorable lipid biomarkers. PL2 (lipidomics, p = 0.02 ) showed stronger associations of triacylglycerides with MUO, whereas phospholipids correlated with MHO. PP5 (proteomics, p = 0.01 ) included interleukin-1 receptor antagonist (IL-1ra) and leptin with positive relations to MUO and galanin that correlated positively to MHO. The group differences in metabolite profiles were to a large extent explained by factors included in the metabolic syndrome. Conclusion. Compared to MUO individuals, corresponding MHO individuals present with a more favorable lipid metabolic profile, accompanied by a downregulation of potentially harmful proteomic biomarkers. This unique and extensive biomarker profiling presents novel data on potentially differentiating traits between these two obese phenotypes.

scholarly journals Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity

2017 ◽  
Vol 242 (7) ◽  
pp. 773-780 ◽  
Author(s):  
Fanyi Zhong ◽  
Mengyang Xu ◽  
Richard S Bruno ◽  
Kevin D Ballard ◽  
Jiangjiang Zhu
Keyword(s):  
Mass Spectrometry ◽  
Metabolic Syndrome ◽  
Metabolic Profiling ◽  
High Performance ◽  
Density Lipoprotein ◽  
Principal Component ◽  
Metabolic Profiles ◽  
The Metabolic Syndrome ◽  
Metabolite Profiles ◽  
Liquid Chromatography Tandem Mass

Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m2) and women ( n = 40; 34.9 ± 6.7 kg/m2), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS–DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4–5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established MetS criteria. To our best knowledge, the findings of this study provide the first evidence that metabolic profiles can be used to differentiate participants with MetS from similarly obese individuals who do not meet established criteria of MetS. Furthermore, the study demonstrated that within MetS participants, their unique metabolic profiles correlated to the number of criteria used for MetS determination. Taken together, this metabolic profiling approach can potentially serve as a novel tool for MetS detection and monitoring, and provide useful metabolic information for future interventions targeting obesity and MetS.

scholarly journals THE CHARACTERISTICS OF SECRETION OF ADIPONECTIN AND ITS RELATIONSHIP WITH PARTICULAR INDICESOF METABOLISM IN MALES OF ABLE-BODIED AGE IN CASE OF OBESITY

2017 ◽  
Vol 23 (6) ◽  
pp. 312-315
Author(s):  
Olga V. Karataeva
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Low Density Lipoproteins ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Metabolically Healthy Obesity ◽  
Significant Difference ◽  
Fasting Glycaemia ◽  
Metabolically Healthy ◽  
Degree Of Severity

The sampling consisted of 79 examined males of able-bodied age. The arterial hypertension stage I and II was established in 58% of them; obesity of various degree of severity was diagnosed in 63% of them; metabolic syndrome according criteria ATP-III was noted in 46.8% of examined patients. The general clinical and anthropometric examination was carried out. The laboratory analyses included estimation of lipidogram, fasting glycaemia and also hormones adiponectin and insulin with following calculation of index of insulin resistance HOMA-IR (Homeostasis Model Assessment of Insulin Resistance). The study was organized to investigate effecting of obesity on secretion of adiponectin and its relationship with indices of lipidogram and level of insulin resistance. The comparative analysis of groups with and absence of obesity established no significant difference in level of adiponectin and indices of lipidogram. the significant differences were established in the levels of basal insulin hence in value of index NOMA-IR that points to hyperinsulinemia and expressed insulin resistance in patients with obesity. The patients were separated in two groups depending on presence of manifestations of metabolic syndrome: with metabolically healthy obesity and metabolically complicated obesity. The analysis established a significant decreasing of level of adiponectin in the group of metabolically complicated obesity accompanied by insulin resistance, dyslipidemia and increased level of glycaemia. The study established no effect of degree of obesity on decreasing of level of adiponectin. The significant differences between levels of adiponectin in comparison between group without obesity and group of metabolically healthy obesity. The correlation analysis in group with obesity demonstrated back-coupling between level of adiponectin and content of total cholesterol, low density lipoproteins and coefficient of atherogenicity. The comparison of groups according median of adiponectin established significant differences in rate of development of metabolic syndrome and value of coefficient of atherogenicity.

scholarly journals Association between metabolically healthy obesity/overweight and cardiovascular disease risk: A representative cohort study in Taiwan

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246378
Author(s):  
Tzu-Lin Yeh ◽  
Hsin-Yin Hsu ◽  
Ming-Chieh Tsai ◽  
Le-Yin Hsu ◽  
Lee-Ching Hwang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cohort Study ◽  
Cox Regression ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Normal Weight ◽  
Metabolically Healthy Obesity ◽  
Cox Regression Analysis ◽  
The Metabolic Syndrome ◽  
Metabolically Healthy

Objectives To investigate the relationship between metabolically healthy obesity and cardiovascular disease risk in Taiwanese individuals. Methods Taiwanese individuals were recruited from a nationwide, representative community-based prospective cohort study and classified according to body mass index as follows: normal weight (18.5–23.9 kilogram (kg)/meter(m)2) and obesity/overweight (≥24 kg/m2). Participants without diabetes, hypertension, and hyperlipidemia and who did not meet the metabolic syndrome without waist circumference criteria were considered metabolically healthy. The study end points were cardiovascular disease morbidity and mortality. Multivariable adjusted hazard ratios and 95% confidence intervals were obtained from a Cox regression analysis. Results Among 5 358 subjects (mean [standard deviation] age, 44.5 [15.3] years; women, 48.2%), 1 479 were metabolically healthy with normal weight and 491 were metabolically healthy with obesity. The prevalence of metabolically healthy obesity/overweight was 8.6% in the Taiwanese general population, which included individuals who were >20 years old, not pregnant, and did not have CVD (n = 5,719). In the median follow-up period of 13.7 years, 439 cardiovascular disease events occurred overall and 24 in the metabolically healthy obesity group. Compared with the reference group, the metabolically healthy obesity group had a significantly higher cardiovascular disease risk (adjusted hazard ratio: 1.74, 95% confidence interval: 1.02, 2.99). Conclusions Individuals with metabolically healthy obesity have a higher risk of cardiovascular disease and require aggressive body weight control for cardiovascular disease control.

Metabolically healthy obesity was significantly associated with increased risk of gallstones

2021 ◽  
Author(s):  
Sailimai Man ◽  
Yongxiang Gao ◽  
Jun Lv ◽  
Mingkun Tong ◽  
Jianchun Yin ◽  
...  
Keyword(s):  
Normal Weight ◽  
Metabolic Health ◽  
Health Check ◽  
Healthy Individuals ◽  
Metabolically Healthy Obesity ◽  
Increased Risk ◽  
History Of ◽  
Normal Body Weight ◽  
Metabolically Healthy ◽  
Cox Proportional Hazard Regression

Objective The risk of gallstones among metabolically healthy obesity (MHO) individuals is largely unexplored. Therefore, the present study investigated the association between MHO and gallstones in a health check-up cohort of Chinese adults. Design A prospective cohort study. Methods Participants included 58,862 individuals from the MJ health check-up cohort aged ≥ 18 years without history of gallstones at baseline. Gallstones were diagnosed using abdominal B-type ultrasound. Metabolically healthy was defined as not having any one of the components of metabolic syndrome. Obesity was identified by body mass index (BMI) and waist circumference (WC). Participants were cross-classified at baseline by metabolic health and obesity. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of gallstones across BMI categories were estimated with Cox proportional hazard regression models. Results During a median follow-up of 3.0 (interquartile range, 1.6-6.1) years, 1,269 participants developed gallstones. Individuals with MHO (HR: 1.95, 95% CI: 1.23, 3.09 for BMI criteria; HR: 1.74, 95% CI: 1.37, 2.21 for WC criteria) had significantly higher risk of gallstones than those with metabolically healthy normal weight. In metabolically healthy individuals, BMI and WC both displayed linear dose-response relationships with gallstones (P for non-linearity > 0.05). The association between MHO and gallstones remained unchanged when using different criteria for metabolic health and obesity. Conclusions MHO was significantly associated with gallstones, suggesting that obesity can independently contribute to gallstones development, even among metabolically healthy individuals. These findings emphasize that metabolically healthy individuals may still benefit from maintaining normal body weight to prevent gallstones.

scholarly journals Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anabel Zabala-Peñafiel ◽  
Geovane Dias-Lopes ◽  
Léa Cysne-Finkelstein ◽  
Fátima Conceição-Silva ◽  
Luciana de Freitas Campos Miranda ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Principal Component ◽  
Clinical Isolates ◽  
In Vitro Susceptibility ◽  
Axenic Amastigotes ◽  
Homogeneous Cluster ◽  
Significant Difference ◽  
American Tegumentary Leishmaniasis

AbstractGlucantime (SbV) is the first-line treatment against American Tegumentary Leishmaniasis. Resistance cases to this drug have been reported and related to host characteristics and parasite phenotypes. In this study, 12 Leishmania (Viannia) braziliensis isolates from patients that presented clinical cure (Responders—R) and relapse or therapeutic failure (Non-responders—NR) after treatment with antimony, were analyzed. These parasites were assessed by in vitro susceptibility to SbIII and SbV, serine proteases activity measured with substrate (z-FR-AMC) and specific inhibitors (TLCK, AEBSF and PMSF). In vitro susceptibility of axenic amastigotes to SbIII showed a significant difference between R and NR groups. The protease assays showed that TLCK inhibited almost 100% of activity in both axenic amastigotes and promastigotes while AEBSF inhibited around 70%, and PMSF showed lower inhibition of some isolates. Principal component and clustering analysis performed with these data yielded one homogeneous cluster with only NR isolates and three heterogeneous clusters with R and NR isolates. Additionally, differential expression of subtilisins (LbrM.13.0860 and LbrM.28.2570) and TXNPx (LbrM.15.1080) was evaluated in promastigotes and axenic amastigotes from both groups. The results showed a higher expression of LbrM.13.0860 and LbrM.15.1080 genes in axenic amastigotes, while LbrM.28.2570 gene had the lowest expression in all isolates, regardless of the parasite form. The data presented here show a phenotypic heterogeneity among the parasites, suggesting that exploration of in vitro phenotypes based on SbIII and serine proteases profiles can aid in the characterization of L. (V.) braziliensis clinical isolates.

scholarly journals Histamine Intolerance: Clinical Characterization and Determination of Serum Diamine Oxidase (Dao) in a Series of Cases and Controls

2020 ◽  
Author(s):  
Peralta Teresa ◽  
Bastías Carla ◽  
Camila Beltran-Ortiz ◽  
Durán Magdalena ◽  
Ramos Verónica ◽  
...  
Keyword(s):  
Diamine Oxidase ◽  
Clinical Manifestations ◽  
Histamine Intolerance ◽  
Significant Difference ◽  
History Of ◽  
Ige Mediated ◽  
Average Serum ◽  
Excessive Accumulation

Abstract Introduction. Histamine intolerance (HIT) is a pathology with an estimated prevalence of 1% in which there is an imbalance between the intake of histamine via the digestive tract and the body's ability to degrade it. This results in an excessive accumulation of histamine that determines the appearance of gastrointestinal, skin, respiratory and neurological symptoms. The enzyme responsible for degrading histamine in the extracellular space is diamine oxidase (DAO); therefore, HIT is caused due to a deficit in the concentration and/or in the activity of this enzyme. Because histamine is the main mediator of the classic symptoms of IgE-mediated allergic reactions, it is difficult to differentiate a true allergy from HIT since it has basically the same clinical manifestations. Objectives. The objective of this study was to perform a clinical characterization of patients with HIT and to determine the usefulness of quantifying serum DAO concentration in the diagnosis of HIT. Method: Twenty-two patients over the age of 18 with a history of histamine intolerance were recruited, in whom IgE-mediated food allergy was ruled out, and 22 healthy patients. Both groups were surveyed and serum DAO concentration was determined. Results: Middle-aged women predominated in the population with HIT. They described a wide variety of symptoms, with a dominance of abdominal pain, bloating, diarrhea, flushing, urticaria, itching, headache and dysmenorrhea. When comparing the average serum DAO concentration in the population with HIT (10.686 U/ml) with the average obtained in the control population (20.664 U/ml), there was a significant difference (p < 0.003). Conclusion. The determination of serum DAO concentration is a useful tool for the diagnosis of HIT.

scholarly journals Species-dependent variation of the gut bacterial communities across Trypanosoma cruzi insect vectors

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240916
Author(s):  
Luisa M. Arias-Giraldo ◽  
Marina Muñoz ◽  
Carolina Hernández ◽  
Giovanny Herrera ◽  
Natalia Velásquez-Ortiz ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Bacterial Communities ◽  
Principal Component ◽  
Rrna Gene ◽  
Insect Vectors ◽  
Infection Frequency ◽  
Alpha And Beta Diversity ◽  
Bacterial Phyla ◽  
Significant Difference

Triatomines (Hemiptera: Reduviidae) are the insect vectors of Trypanosoma cruzi, the causative agent of Chagas disease. The gut bacterial communities affect the development of T. cruzi inside the vector, making the characterization of its composition important in the understanding of infection development. We collected 54 triatomine bugs corresponding to four genera in different departments of Colombia. DNA extraction and PCR were performed to evaluate T. cruzi presence and to determine the discrete typing unit (DTU) of the parasite. PCR products of the bacterial 16S rRNA gene were pooled and sequenced. Resulting reads were denoised and QIIME 2 was used for the identification of amplicon sequence variants (ASVs). Diversity (alpha and beta diversity) and richness analyses, Circos plots, and principal component analysis (PCA) were also performed. The overall T. cruzi infection frequency was 75.9%, with TcI being the predominant DTU. Approximately 500,000 sequences were analyzed and 27 bacterial phyla were identified. The most abundant phyla were Proteobacteria (33.9%), Actinobacteria (32.4%), Firmicutes (19.6%), and Bacteroidetes (7.6%), which together accounted for over 90% of the gut communities identified in this study. Genera were identified for these main bacterial phyla, revealing the presence of important bacteria such as Rhodococcus, Serratia, and Wolbachia. The composition of bacterial phyla in the gut of the insects was significantly different between triatomine species, whereas no significant difference was seen between the state of T. cruzi infection. We suggest further investigation with the evaluation of additional variables and a larger sample size. To our knowledge, this study is the first characterization of the gut bacterial structure of the main triatomine genera in Colombia.

scholarly journals Association between the phenotype of metabolically healthy obesity and the risk of myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Malyutina ◽  
S Mustafina ◽  
D Vinter ◽  
O Rymar ◽  
L Shcherbakova ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Relative Risk ◽  
Cox Regression ◽  
Population Sample ◽  
Funding Source ◽  
Metabolically Healthy Obesity ◽  
Men And Women ◽  
The Metabolic Syndrome ◽  
Metabolically Healthy ◽  
Metabolically Unhealthy Obesity

Abstract Aim This study aimed to investigate the associations between the metabolically healthy obesity (MHO) and the risk of myocardial infarction (MI) in a Russian population sample. Materials and methods A random population sample of men and women aged 45–69 years old at baseline was examined in 2003–2005 in a Russian city; after that the cohort was followed-up for 12 years on the average (2003–2016). A sub-cohort of subjects with body mass index (BMI) ≥30 kg/m2 at baseline was selected for present study (3157 individuals, 73.2% women); of those, 3008 subjects free from baseline history of MI/acute CHD was included for analysis. The data on incident myocardial infarction (MI) were ascertained from register of MI, two repeated examinations and repeated postal interviews during 12-year follow-up of the cohort. We used two definitions of MHO: by NCEP ATPIII, 2001 (the presence of 2 or less components of the metabolic syndrome) and by IDF 2005 (waist circumference (WC) ≥94 cm in men and ≥80 cm in women regardless of risk factors). Multivariable Cox regression was conducted using the SPSS package (V. 13.0). Results The prevalence of MHO at baseline ranged from 20% (by IDF) to 45% (by NCEPATPIII) in obese sub-cohort. Among subjects with MHO at baseline, about one half of subjects developed metabolically unhealthy obesity phenotype (MUO) during 12-years. Women were more likely to retain MHO (32%) and more frequent transited from MUO to MHO (14%) compared to men (22% and 6% by IDF criteria, correspondently) during 12 years. The relative risk of incident MI in subjects with MUO at baseline was 1.9 times higher than in those with MHO (HR 1.9, 95% CI 1.2–2.9) by NCEPATP III. Among men, the relative risk of MI in those with MUO (by NCEP ATP III) was 2 times higher than in a group with MHO (HR 2.1, 95% CI 1.1–4.0). Among women, the relative risk of MI in those with MUO (by NCEP ATP III) was 2.2 (95% CI 1.2- 4.2) compared to MHO group. Using the IDF criteria, the relative risk of MI in MUO vs. MHO was 2.2 (95% CI 0.9–5.7) in men and 2.2 (95% CI: 0.9–5.7) in women. Conclusions In this study population, men aged 45–69 have more frequent progression from metabolically healthy to metabolically unhealthy obesity during 12 years compared to women. The 12-year risk of incident MI in subjects with MUO was approximately twice higher compared to MHO and the excess risk was similar in men and women. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Wellcom Trust

scholarly journals Vasodilator responses and endothelin-dependent vasoconstriction in metabolically healthy obesity and the metabolic syndrome

2015 ◽  
Vol 309 (9) ◽  
pp. E787-E792 ◽  
Author(s):  
Francesca Schinzari ◽  
Micaela Iantorno ◽  
Umberto Campia ◽  
Nadia Mores ◽  
Valentina Rovella ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Vascular Reactivity ◽  
Forearm Blood Flow ◽  
Control Group ◽  
Obese Patients ◽  
Metabolic Abnormalities ◽  
Metabolically Healthy Obesity ◽  
Arterial Infusion ◽  
The Metabolic Syndrome ◽  
Metabolically Healthy

Patients with metabolically healthy obesity (MHO) do not present the cluster of metabolic abnormalities that define the metabolic syndrome (MetS). Whether MHO is associated with lower impairment of vasoreactivity than the MetS is unknown. For this purpose, forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and/or the selective endothelin type A (ETA) receptor blocker BQ-123 in 119 obese individuals with MHO ( n = 34) or with the MetS ( n = 85) and in healthy lean controls ( n = 56). ACh and SNP caused a significant vasodilation in both obese and lean participants (all P < 0.001). However, the response to both agents was significantly lower in the obese than in the control group (both P < 0.001). Among the obese participants, the reactivity to ACh was higher in MHO than in MetS patients, whereas the responsiveness to SNP was equally impaired in both groups ( P = 0.45). Infusion of BQ-123 significantly increased FBF in obese patients ( P < 0001), but not in the lean participants; hence, FBF following ETA receptor blockade was higher in both obese groups than in controls (both P < 0.001). FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO ( P = 0.007). In conclusion, patients with MHO have abnormal vascular reactivity, although their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity is associated with vascular damage independent of those metabolic abnormalities underlying the MetS.

scholarly journals Serine Proteases Profiles of Leishmania (Viannia) Braziliensis Clinical Isolates With Distinct Susceptibilities to Antimony

2021 ◽  
Author(s):  
Anabel Zabala-Peñafiel ◽  
Geovane Dias-Lopes ◽  
Léa Cysne-Finkelstein ◽  
Fátima Conceição-Silva ◽  
Luciana de Freitas Campos Miranda ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Principal Component ◽  
Clinical Isolates ◽  
First Line ◽  
Axenic Amastigotes ◽  
Homogeneous Cluster ◽  
Significant Difference ◽  
Tryparedoxin Peroxidase

Abstract Glucantime® (SbV) is the first-line treatment against leishmaniasis in South America. Its effectiveness has been associated with modulation of the parasite detoxification system that, in turn, is related to serine proteases such as subtilisins. In this study, 12 Leishmania (Viannia) braziliensis isolates from patients that presented clinical cure (Responders - R) and relapse or therapeutic failure (Non-responders - NR) were used. The parasites were assessed by in vitro susceptibility to SbIII and SbV, serine proteases activity – measured with z-FR-AMC as substrate and specific inhibitors – and expression of subtilisins and tryparedoxin-peroxidase (TXNPx). In vitro susceptibility of axenic amastigotes to SbIII showed a significant difference between R and NR groups. TLCK inhibited almost 100 % of activity in both axenic amastigotes and promastigotes while AEBSF inhibited around 70 %, and PMSF showed lower inhibition of specific isolates. Principal component and clustering analysis yielded one homogeneous cluster with only NR isolates and three heterogeneous clusters with R and NR isolates. Additionally, transcripts of subtilisins (LbrM.13.0860 and LbrM.28.2570) and TXNPx (LbrM.15.1080) were detected in promastigotes and axenic amastigotes from both groups. The data presented here show a phenotypic heterogeneity among the parasites, suggesting that exploration of in vitro phenotypes based on SbIII and serine proteases profiles can aid in the characterization of L. (V.) braziliensis clinical isolates.

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