Modulation of the inflammatory response to LPS by the recruitment and activation of brown and brite adipocytes in mice.

OBJECTIVES Numerous studies have shown that the recruitment and activation of thermogenic adipocytes, which are brown and beige/brite, reduces the mass of adipose tissue and normalizes abnormal glycaemia and lipidaemia. However, the impact of these adipocytes on the inflammatory state of adipose tissue is still not well understood, especially in response to endotoxaemia, which is a major aspect of obesity and metabolic diseases. METHODS First, we analysed the phenotype and metabolic function of white and brite primary adipocytes in response to lipopolysaccharide (LPS) treatment in vitro. Then, 8-week-old male BALB/c mice were treated for one week with a β3-adrenergic receptor agonist (CL316,243, 1 mg/kg/day) to induce recruitment and activation of brown and brite adipocytes and were subsequently injected with LPS (E. coli lipopolysaccharide, i.p., 100 μg/mouse) to generate acute endotoxaemia. The metabolic and inflammatory parameters of the mice were analysed 6 hours later. RESULTS Our results showed that in response to LPS, thermogenic activity promoted a local anti-inflammatory environment with high secretion of IL-1RA without affecting other anti- or pro-inflammatory cytokines. Interestingly, activation of brite adipocytes reduced the LPS-induced secretion of leptin. However, thermogenic activity and adipocyte function were not altered by LPS treatment in vitro or by acute endotoxaemia in vivo. CONCLUSION In conclusion, these results suggest an IL-1RA-mediated immunomodulatory activity of thermogenic adipocytes specifically in response to endotoxaemia. This encourages potential therapy involving brown and brite adipocytes for the treatment of obesity and associated metabolic diseases.