Preadipocytes mediate lipopolysaccharide-induced inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes

Soonkyu Chung, Kathleen LaPoint, Kristina Martinez, Arion Kennedy, Maria Boysen Sandberg, Michael K. McIntosh

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

Recent data suggest that proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. However, characterization of the cell types involved in inflammation and how these cells promote insulin resistance in human adipocytes are unclear. We simulated acute inflammation using the endotoxin lipopolysaccharide (LPS) to define the roles of nonadipocytes in primary cultures of human adipocytes. LPS induction of the mRNA levels of proinflammatory cytokines (e.g. IL-6, TNF-α, and IL-1β) and chemokines (e.g. IL-8, monocyte chemoattractant protein-1) occurred primarily in the nonadipocyte fraction of newly differentiated human adipocytes. Nonadipocytes were characterized as preadipocytes based on their abundant mRNA levels of preadipocyte markers preadipocyte factor-1 and adipocyte enhancer protein-1 and only trace levels of markers for macrophages and myocytes. The essential role of preadipocytes in inflammation was confirmed by modulating the degree of differentiation in the cultures from approximately 0-90%. LPS-induced proinflammatory cytokine/chemokine expression and nuclear factor-κB and MAPK signaling decreased as differentiation increased. LPS-induced cytokine/chemokine expression in preadipocytes was associated with: 1) decreased adipogenic gene expression, 2) decreased ligandinduced activation of a peroxisome proliferator activated receptor (PPAR)-γ reporter construct and increased phosphorylation of PPARγ, and 3) decreased insulin-stimulated glucose uptake. Collectively, these data demonstrate that LPS induces nuclear factor-κB- and MAPK-dependent proinflammatory cytokine/chemokine expression primarily in preadipocytes, which triggers the suppression of PPARγ activity and insulin responsiveness in human adipocytes.

Original languageEnglish (US)
Pages (from-to)5340-5351
Number of pages12
JournalEndocrinology
Volume147
Issue number11
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Preadipocytes mediate lipopolysaccharide-induced inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes'. Together they form a unique fingerprint.

  • Cite this