Physiology Research

Obesity Surgery

, Volume 20, Issue 12, pp 1682-1689

First online:

The Decrease of Serum Levels of Human Neutrophil Alpha-Defensins Parallels with the Surgery-Induced Amelioration of NASH in Obesity

  • Melania MancoAffiliated withScientific Directorate, Bambino Gesù Hospital and Research Institute Email author 
  • , José Manuel Fernandez-RealAffiliated withSection of Diabetes, Endocrinology and Nutrition, University Hospital of Girona, Intitut d’Investigació Biomèdica de Girona (IDibGi) and CIBEROBN Fisiopatología de la Obesidad y Nutrición
  • , Fabio Maria VecchioAffiliated withDepartment of Pathology, Catholic University
  • , Valerio VelloneAffiliated withDepartment of Pathology, Catholic University
  • , José María MorenoAffiliated withSection of Diabetes, Endocrinology and Nutrition, University Hospital of Girona, Intitut d’Investigació Biomèdica de Girona (IDibGi) and CIBEROBN Fisiopatología de la Obesidad y Nutrición
  • , Vincenzo TondoloAffiliated withDepartment of Surgery, Catholic University
  • , GianFranco BottazzoAffiliated withScientific Directorate, Bambino Gesù Hospital and Research Institute
  • , Giuseppe NanniAffiliated withDepartment of Surgery, Catholic University
  • , Geltrude MingroneAffiliated withDepartment of Internal Medicine, Catholic University

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Abstract

Background

Innate immune system participates actively into inflammatory processes, with immune cells and liver secreting a number of immune peptides. Among them, both soluble CD14 receptor (sCD14) and human neutrophil alpha-defensins (HNDs) may represent serum markers of necro-inflammation in obese patients with non-alcoholic fatty liver disease.

Methods

To verify this hypothesis, we investigated changes in circulating levels of sCD14 and HNDs in 11 severely obese young women following surgery-induced weight loss (bilio-pancreatic diversion). Patients were evaluated before surgery and 2 years later, with NAS score evaluated on liver biopsies and whole body glucose uptake (M value) by euglycemic hyperinsulinemic clamp.

Results

NAS score improved in nine patients [median NAS score in the whole sample, 6 (5–6) vs. 3 (3–4), p = 0.016]. Serum concentrations of HNDs decreased significantly in all (p = 0.016), whilst sCD14 increased only in the nine women who showed the amelioration of the NAS score [2.4 (1.7–2.6) vs. 2.6 (2.3–3.3) μg/ml, p = 0.001]. NAS score and HNDs correlated significantly both before (r o = 0.671, p = 0.02) and after weight loss (r o = 0.683, p = 0.029), NAS score and sCD14 only before surgery (r o = 0.605, p = 0.04). The M value increased in all patients [2.67 (1.99–3.01) vs. 6.89 (6.35–7.32) mg kg FFM −1  min−1; p = 0.01], but independently of NAS score changes.

Conclusions

Changes in levels of HNDs and sCD14 accompany those in hepatic necro-inflammation due to surgical-induced weight loss. Further studies are needed to verify any causative role of these peptides in non-alcoholic steatohepatitis.

Keywords

Bariatric surgery Human neutrophil alpha-defensins (HNDs) Non-alcoholic fatty liver disease (NAFLD) Inflammation Innate immune system Insulin sensitivity Obesity Non-alcoholic steatohepatitis (NASH) Soluble CD14 receptor (sCD14)