The decrease of serum levels of human neutrophil alpha-defensins parallels with the surgery-induced amelioration of NASH in obesity.
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.
Manco
Melania
M
Scientific Directorate, Bambino Gesù Hospital and Research Institute, Rome, Italy. melaniamanco@tiscali.it
Fernandez-Real
José Manuel
JM
Vecchio
Fabio Maria
FM
Vellone
Valerio
V
Moreno
José María
JM
Tondolo
Vincenzo
V
Bottazzo
GianFranco
G
Nanni
Giuseppe
G
Mingrone
Geltrude
G
D000328:Adult; D015904:Biliopancreatic Diversion; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis / Q000601:surgery; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance; D018950:Lipopolysaccharide Receptors / Q000097:blood; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000097:blood* / Q000601:surgery; D015431:Weight Loss; D055815:Young Adult; D023084:alpha-Defensins / Q000097:blood*
D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D023084:alpha-Defensins