Endocrine Abstracts

Introduction: The corticotrophin-releasing factor (CRF) family of neuropeptides and their receptors affect innate immunity. A fully working peripheral CRF system is present in adipose tissue. In obesity, macrophages and adipocytes interact causing local and systemic inflammation. In addition, macrophages and adipocytes share common characteristics including production of inflammatory cytokines in response to lipopolysaccharides (LPS) via the toll-like receptor-4 (TLR4) which both macrophages and adipocytes express. Aim of this work was to examine the effects of CRF1 and CRF2 agonists and antagonists on the immune machinery of adipocytes.

Description of methods: We have used 3T3L1 mouse pre- and differentiated adipocytes. IL6/IL8 were measured by ELISA, the TLR4 receptor by RT-PCR and FACS analysis.

Results: Our data are as follows: i) LPS induced TLR4 expression and the production of interleukins IL6 and IL8 by mature adipocytes but not by pre-adipocytes. ii) LPS induced the differentiation of pre-adipocytes to adipocytes. iii) pre-adipocytes and adipocytes expressed the CRF1 and CRF2 receptors. iv) CRF1 agonists decreased basal and LPS-induced differentiation of pre-adipocytes. v) CRF2 agonists transiently suppressed the expression (transcript and protein) of TLR4 as well as the production of interleukins by pre-adipocytes. vi) both CRF receptor agonists inhibited basal and LPS-induced expression of TLR4 as well as the production of interleukins and adipokines (adiponectin and leptin) in mature adipocytes.

Conclusion: Our results indicate that CRF neuropeptides suppress TLR4 expression in adipocytes via CRF2, an effect containing their pro-inflammatory activity. They also suppress the differentiation of pre-adipocytes exclusively via CRF1. Thus, CRF appears to exert an anti-inflammatory effect in adipocytes.