The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα.

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.

• Authors: Elsa Maymó-Masip, Sonia Fernández-Veledo, Antonio Garcia España, Ana Vázquez-Carballo, Francisco Jóse Tinahones, Eduardo García-Fuentes, Lourdes Garrifo-Sanchez, Maria del Mar Rodriguez, Joan Vendrell, Matilde R Chacón
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 98 Issue 8 Pg. E1323-33 (Aug 2013) ISSN: 1945-7197 [Electronic] United States
• PMID: 23783093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokine TWEAK
• Cytokines
• Fatty Acids, Nonesterified
• TNFSF12 protein, human
• Tumor Necrosis Factor-alpha
• Tumor Necrosis Factors

Topics

• Adipocytes (immunology)
• Adult
• Bariatric Surgery
• Body Mass Index
• Cytokine TWEAK
• Cytokines (biosynthesis)
• Fatty Acids, Nonesterified (blood)
• Female
• Humans
• Macrophages (metabolism)
• Male
• Middle Aged
• Obesity (immunology, surgery)
• Tumor Necrosis Factor-alpha (physiology)
• Tumor Necrosis Factors (blood)