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Somatostatin Is Expressed and Secreted by Human Adipose Tissue upon Infection and Inflammation

Department of Research (D.S., P.L.), Division of Endocrinology, Diabetology and Clinical Nutrition (H.Z., M.C.-C., U.K., B.M.), and Department of Visceral Surgery (I.L.), University Hospitals, CH-4031 Basel, Switzerland

Address all correspondence and requests for reprints to: Dalma Seboek, Department of Research, University Hospitals, Hebelstrasse 20, CH-4031 Basel, Switzerland. E-mail: Dalma.Seboek{at}unibas.ch.

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-1ß treatments. LPS- and IL-1ß-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 TNF/IL-1ß/LPS-treated adipocytes. SRIF protein was visualized by immunohistochemistry in explanted minced adipose tissue after overnight incubation in culture medium supplemented with combined IL-1ß 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.

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