Publication: The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα.
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Identifiers
Date
2013-08
Authors
Maymó-Masip, Elsa
Fernández-Veledo, Sonia
García España, Antonio
Vázquez-Carballo, Ana
Tinahones, Francisco José
García-Fuentes, Eduardo
Garrifo-Sánchez, Lourdes
Rodríguez, María del Mar
Vendrell, Joan
Chacón, Matilde R
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Endocrine Society
Metrics
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Abstract
CONTEXT
Soluble TNF-like weak inducer of apoptosis (sTWEAK) is generated by the intracellular proteolytic cleavage of full-length membrane-bound TNF-like weak inducer of apoptosis (mTWEAK). sTWEAK levels are reduced in diseases with an inflammatory component. Additionally, sTWEAK hampers TNFα activity in human cells.
OBJECTIVES
The objectives of the study were as follows: 1) to determine circulating sTWEAK in severe obesity and after bariatric surgery; 2) to study m/sTWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14) protein expression in sc adipose tissue (SAT) of severely obese subjects, in SAT stromal vascular fraction (SVF), and isolated adipocytes and in human monocyte-derived macrophages; and 3) to explore, on human adipocytes, the sTWEAK effect on TNFα proinflammatory activity.
DESIGN
sTWEAK levels were measured in cohort 1: severely obese subjects (n = 23) and a control group (n = 35); and in cohort 2: (n = 23) severely obese subjects before and after surgery. The m/sTWEAK and Fn14 expressions were determined in SAT biopsies, SVF, and isolated adipocytes from severely obese and control subjects and in human monocyte-derived macrophages. In human primary cultured adipocytes, sTWEAK pretreated and TNFα challenged, IL-6, IL-8, and adiponectin protein and gene expressions were determined and nuclear factor-κ B and MAPK signaling analyzed.
RESULTS
sTWEAK levels were reduced in severely obese subjects. After surgery, sTWEAK levels rose in 69% of patients. mTWEAK protein expression was increased in SAT and SVF of severely obese subjects, whereas Fn14 was up-regulated in isolated adipocytes. M2 human monocyte-derived macrophages overexpress mTWEAK. In human adipocytes, sTWEAK down-regulates TNFα cytokine production by hampering TNFα intracellular signaling events.
CONCLUSION
The decrease of sTWEAK in severely obese patients may favor the proinflammatory activity elicited by TNFα.
Description
Journal Article; Research Support, Non-U.S. Gov't;
MeSH Terms
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Bariatric Surgery
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Nonesterified
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Macrophages
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors::Tumor Necrosis Factor-alpha
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors
Medical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Adipocytes
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Bariatric Surgery
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Nonesterified
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Macrophages
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors::Tumor Necrosis Factor-alpha
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors
Medical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Adipocytes
DeCS Terms
CIE Terms
Keywords
Cirugía bariátrica, Índice de masa corporal, Citocinas, Ácidos grasos no esterificados, Macrófagos, Obesidad, Factor de necrosis tumoral alfa, Factores de necrosis tumoral, Adipocitos
Citation
Maymó-Masip E, Fernández-Veledo S, García España A, Vázquez-Carballo A, Tinahones FJ, García-Fuentes E, et al. The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα. J Clin Endocrinol Metab. 2013; 98(8):E1323-33