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The Effects of Bariatric Surgery-Induced Weight Loss on Adipose Tissue in Morbidly Obese Women Depends on the Initial Metabolic Status

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Abstract

Background

Adipose tissue (AT) dysfunction in obesity is commonly linked to insulin resistance and promotes the development of metabolic disease. Bariatric surgery (BS) represents an effective strategy to reduce weight and to improve metabolic health in morbidly obese subjects. However, the mechanisms and pathways that are modified in AT in response to BS are not fully understood, and few information is still available as to whether these may vary depending on the metabolic status of obese subjects.

Methods

Abdominal subcutaneous adipose tissue (SAT) samples were obtained from morbidly obese women (n = 18) before and 13.3 ± 0.37 months after BS. Obese women were stratified into two groups: normoglycemic (NG; Glu < 100 mg/dl, HbA1c <5.7 %) or insulin resistant (IR; Glu 100–126 mg/dl, HbA1c 5.7–6.4 %) (n = 9/group). A multi-comparative proteomic analysis was employed to identify differentially regulated SAT proteins by BS and/or the degree of insulin sensitivity. Serum levels of metabolic, inflammatory, and anti-oxidant markers were also analyzed.

Results

Before surgery, NG and IR subjects exhibited differences in AT proteins related to inflammation, metabolic processes, the cytoskeleton, and mitochondria. BS caused comparable weight reductions and improved glucose homeostasis in both groups. However, BS caused dissimilar changes in metabolic enzymes, inflammatory markers, cytoskeletal components, mitochondrial proteins, and angiogenesis regulators in NG and IR women.

Conclusions

BS evokes significant molecular rearrangements indicative of improved AT function in morbidly obese women at either low or high metabolic risk, though selective adaptive changes in key cellular processes occur depending on the initial individual’s metabolic status.

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Acknowledgements

This work was funded by MINECO/FEDER (BFU2010-17116; BFU2013-44229-R), J. Andalucia/FEDER (PI-0269/2008; CTS-03039, CTS-6606), and CIBEROBN (Instituto de Salud Carlos III), Spain. D.A.C. was supported by the Nicolás Monardes program of the Andalusian Ministry of Health (C-0015-2014). We thank Jana Alonso (Proteomic platform of the Health Research Institute of Santiago (IDIS), University of Santiago de Compostela, Spain) and the Proteomics Facilities of the IMIBIC/University of Córdoba-SCAI (ProteoRed, PRB2-ISCIII, supported by grant PT13/0001) for their help with mass spectrometry studies. We thank Laura Molero (Dept. of Cell Biology, Physiology and Immunology; IMIBIC/Reina Sofia University Hospital/University of Cordoba, CIBEROBN, Spain) for her technical assistance.

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Authors and Affiliations

  1. Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Reina Sofia University Hospital/University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain

    Natalia Moreno-Castellanos, Rocío Guzmán-Ruiz, Juan R. Peinado, Rafael Vázquez-Martínez & María M. Malagón

  2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain

    Natalia Moreno-Castellanos, Rocío Guzmán-Ruiz, Juan R. Peinado, Rafael Vázquez-Martínez & María M. Malagón

  3. Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científícas/Universidad de Sevilla, Avda. Manuel Siurot, s/n, Sevilla, 41013, Spain

    David A. Cano, Ainara Madrazo-Atutxa, Jose L. Pereira-Cunill, Pedro Pablo García-Luna & Alfonso Leal-Cerro

  4. Unit of Innovation in Minimally Invasive Surgery, Unidad de Gestión Clínica de Cirugía, Hospital Universitario Virgen del Rocío, Sevilla, Spain

    Salvador Morales-Conde & Maria Socas-Macias

Authors
  1. Natalia Moreno-Castellanos
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  2. Rocío Guzmán-Ruiz
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  7. Pedro Pablo García-Luna
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  8. Salvador Morales-Conde
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  9. Maria Socas-Macias
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  11. Alfonso Leal-Cerro
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  12. María M. Malagón
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Corresponding authors

Correspondence to Alfonso Leal-Cerro or María M. Malagón.

Ethics declarations

Informed consent was obtained from all individual participants included in the study, which was approved by the Hospital’s Ethical Committee. All reported investigations were carried out in accordance with the principles of the Declaration of Helsinki.

Conflict of Interest

The authors declare that they have no competing interests.

Financial Support

This work was funded by MINECO/FEDER (BFU2010-17116; BFU2013-44229-R), J. Andalucia/FEDER (PI-0269/2008; CTS-03039; CTS-6606), and CIBERobn (Instituto de Salud Carlos III), Spain.

Electronic Supplementary Material

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Supplementary Figure 1

Uncropped Ponceau images for the different proteins measured by western blotting. (A) DLDH, (B) TCPB and VEGF, (C) AL1A1, (D) SYWC, (E) PGC-1α and JNK, (F) perilipin, (G) IMMT, Adiponectin and p-JNK, and (H) vimentin. (GIF 23 kb)

High resolution image (TIF 421 kb)

Supplementary Figure 2

Decyder software outputs showing the relative abundance of the spots in relation to the internal standard. Graphs show quantitative data of 30 differentially expressed proteins (p < 0.05) identified by the 2D-DIGE analysis in the multicomparative analysis (Suppl. Table 2). TRFE (serotransferrin), PCKGM (Phosphoenolpyruvate carboxykinase), A1BG (Alpha-1B-glycoprotein), FIBB (Fibrinogen beta), CATA (Catalase), TUBB5 (Tubulin beta), PLCD1 (Phosphodiesterase delta-1), AMPL (Cytosol aminopeptidase), ANT3 (Serpin C1), A2MG (Alpha-2-macroglobulin), ANXA6 (Annexin A6), BLVRB (Flavin reductase), ALBU (Serum albumin), IGHM (Ig mu chain C region), IGHG4 (Ig gamma-4 chain C region), KCRB (Creatine kinase B-type), PLIN1 (Perilipin-1), VAT1 (Synaptic vesicle membrane 1), PRDX6 (Peroxiredoxin-6), CH60 (60 kDa heat shock protein), FIBG (Fibrinogen gamma), ANXA1 (Annexin A1), UGPA (Uridylyl transferase), ACOT1 (Acyl-coenzyme A thioesterase), CRYAB (Alpha-crystallin B), HSPB1 (Heat shock protein beta-1), HS71L (Heat shock 70 kDa), SODM (Superoxide dismutase mitochondrial), GRP78 (78 kDa glucose-regulated protein), SEPT11 (Septin 11). (GIF 176 kb)

High resolution image (TIF 726 kb)

Supplementary Figure 3

Metabolic pathway analysis and chart of biological processes of the 37 differentially expressed proteins identified by 2D-DIGE in SAT of NG vs. IR obese subjects at PRE- and POST-BS (see Table 2). (A) Metabolic pathway analysis of the proteomic data by IPA allowed for the identification of one statistically significant interaction map corresponding to Cell Death and Survival, Carbohydrate Metabolism and Inflammatory Disease. The proteins that were identified to belong to this pathway are labeled in orange. (B) Chart of biological processes of the proteins identified by 2D-DIGE. Classification of the identified proteins was performed using PANTHER. Proteins related to metabolic process, cellular process, and immune system process were significantly regulated as determined by the Bonferroni correction for multiple testing used in the calculation of PANTHER p values. Significant differences were considered at p < 0.05. (C) Comparison of human adipose tissue proteome data sets. The colored circles represent lists of proteins differentially expressed (both up and down) between groups with p < 0.05. The resulting protein groups represent proteins differentially expressed between all obese participants Post-BS vs. Pre-BS (pink), IR vs. NG obese women at Pre-BS (purple), NG Post-BS vs. Pre-BS (green), IR Post-BS vs. Pre-BS (yellow), and IR vs. NG at Post-BS (blue). The Venn diagram comparison indicates proteins whose expression changes are shared by the different comparison groups. The overlapping regions indicate the protein expression changes induced by different conditions. (GIF 185 kb)

High resolution image (TIF 819 kb)

Supplementary Table 1

Antibodies used for Western blot studies. (DOCX 16 kb)

Supplementary Table 2

Proteins identified by MALDI-TOF/TOF differentially expressed between normoglycemic (NG) and insulin resistant (IR) women in subcutaneous adipose tissue before (PRE) and after (POST) bariatric surgery (BS). (DOCX 49 kb)

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Moreno-Castellanos, N., Guzmán-Ruiz, R., Cano, D.A. et al. The Effects of Bariatric Surgery-Induced Weight Loss on Adipose Tissue in Morbidly Obese Women Depends on the Initial Metabolic Status. OBES SURG 26, 1757–1767 (2016). https://doi.org/10.1007/s11695-015-1995-x

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