Somatostatin is expressed and secreted by human adipose tissue upon infection and inflammation.
Somatostatin (SRIF) is a well-known neuroendocrine secretion product. SRIF expression and secretion are induced after inflammation in murine macrophages and in endotoxin-injected sheep and pigs. Because adipocytes have been demonstrated to produce numerous cytokines and peptide hormones, we investigated the expression of SRIF and its receptors (SSTR1-5) in human adipose tissue after inflammatory stimulation in vitro and in tissues from patients with septic disease.Preadipocyte-derived adipocytes, mesenchymal stem cell-derived adipocytes, and mature explanted adipocytes expressed SRIF-mRNA after endotoxin [lipopolysaccharide (LPS)] or IL-1beta treatments. LPS- and IL-1beta-mediated SRIF-mRNA induction was blocked by pretreatment with dexamethasone. Using cocultures and quantitative real-time PCR, we demonstrate adipocyte SRIF induction by secretion factors from activated peripheral blood mononuclear cell-derived macrophages. In contrast to basal adipocytes, SRIF protein was detected in culture supernatants of LPS-treated and of combined TNFalpha/IL-1beta/LPS-treated adipocytes. SRIF protein was visualized by immunohistochemistry in explanted minced adipose tissue after overnight incubation in culture medium supplemented with combined IL-1beta and LPS. In septic patients, expression of SRIF-mRNA and SRIF protein was found in visceral, but not in sc, adipose tissue. Adipocyte mRNA abundance of SSTR 1-5 was differentially regulated by inflammatory treatments.Thus, human visceral adipose tissue secretes SRIF during inflammation and sepsis and expresses several SSTRs. It is tempting to speculate that visceral adipose tissue-derived SRIF plays a modulatory role in the immunological and metabolic response to inflammation.
Department of Research, University Hospitals, Hebelstrasse 20, CH-4031 Basel, Switzerland. Dalma.Seboek@unibas.ch
Dalma
D
Seboek
Philippe
P
Linscheid
Henryk
H
Zulewski
Igor
I
Langer
Mirjam
M
Christ-Crain
Ulrich
U
Keller
Beat
B
Müller
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology*; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D006801:Humans; D008565:Membrane Proteins; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000235:genetics; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D013004:Somatostatin / Q000235:genetics* / Q000378:metabolism*
D008565:Membrane Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C098681:somatostatin receptor subtype-4; C101130:somatostatin receptor type 1; D013004:Somatostatin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2