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Of women and men: sexual dimorphism revealed in type 2 diabetes adipose tissue by redox proteomics

AuthorsGómez-Serrano, María; Camafeita, Emilio; Peral, Belén ; Vázquez, Jesús
Issue Date4-Mar-2019
CitationVI Jornadas de Jóvenes Investigadores en Proteómica (2019)
Abstract[Introduction]: The prevalence of type 2 diabetes (T2DM) is rising globally due to, among other factors, obesity, physical inactivity, and aging superimposed on a genetic predisposition. However, little is known about the role for adipose tissue mitochondria in these conditions.
[Aim]: We have recently validated the antioxidant response as a gender-specific hallmark of sexual dimorphism in adipose tissue. Since the mitochondrion is recognized as the main source of oxidative stress, we aimed at investigating the impact of gender on the adipocyte mitochondrial proteome from obese diabetic patients.
[Material & Methods]: Mitochondrial samples were obtained from adipocytes previously isolated from visceral adipose tissue biopsies collected from morbidly obese patients (BMI > 35 kg/m2) suffering T2DM who were submitted for bariatric surgery. Protein abundance and redox differences between women and men suffering T2DM were assessed following a high-throughput approach encompassing differential alkylation of reduced and reversibly oxidized Cys (FASILOX), isobaric labelling (iTRAQ) and LC-MS/MS. [Results]: LC-MS/MS analysis allowed the identification of 15,763 peptides at 1% FDR, corresponding to 2,895 proteins in the mitochondrial extracts. Of note, 754 proteins were annotated in the current version of Human MitoCarta v.2 (68% coverage). FASILOX technology allowed the identification of 277 oxidized and 1990 reduced Cys-containing peptides. According to the WSPP model, Cys oxidation was globally increased in diabetic men compared to women. Enrichment analyses showed that oxidation was focalized on the oxidative phosphorylation (OXPHOS) system, especially in Complex I (p <0.001, FDR 1%).
[Conclusions]: Under T2DM, increased oxidation was found in the adipocyte mitochondria from male patients as compared to females. The identification of gender-matched oxidation targets in T2DM may help to improve the therapeutic approaches currently available for these patients.
DescriptionTrabajo presentado en las VI Jornadas de Jóvenes Investigadores en Proteómica celebradas en Madrid (España) del 4 al 5 de marzo de 2019.
Appears in Collections:(IIBM) Comunicaciones congresos
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