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Proinflammatory cytokine secretion from preadipocytes decreases PPARg expression and activity in primary cultures of human adipocytes

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 in adipose tissue is unclear. To delineate the role that non‐adipocytes play in inflammation, primary cultures of newly‐differentiated human stromal vascular cells containing ~50% adipocytes and ~50% non‐adipocytes were stimulated with LPS for 3 h. Subsequently, non‐adipocytes were fractionated from adipocytes by centrifugation in 6% iodixanol (1.03g/ml) and gene expression in each fraction was quantified by qPCR. LPS induction of proinflammatory cytokine mRNA (IL‐6, IL‐8, TNFα, IL‐1β, COX‐2) occurred primarily in non‐adipocytes. Non‐adipocytes were characterized as preadipocytes based on high mRNA levels of preadipocyte markers Pref‐1 and adipocytes enhancer protein‐1(AEBP‐1) and only trace levels of macrophage (CD68 and Mac‐1) and myocyte (MyoD) markers. LPS‐induced cytokine expression in preadipocytes was associated with suppression of peroxisome proliferator activated receptor (PPAR) γ and adiponectin gene expression in adipocytes. In parallel, LPS treatment increased PPARγ phosphorylation and decreased the activity of a luciferase reporter construct containing a PPARγ response element, indicating that LPS attenuates PPARγ activity. Collectively, these data demonstrate that LPS induces proinflammatory gene expression in preadipocytes, leading to suppression of PPARγ activity in adipocytes, thereby impairing insulin sensitivity.