Endocrine Abstracts

Obesity is associated with low-grade chronic inflammation. Studies demonstrated that RANTES and CCR5 mRNA levels were significantly increased in visceral adipose tissue of obese patients compared with lean control. However, the role of CCR5 activation on pathogenesis of obesity is not clear. The purpose of this study is to explore the effects of CCR5 activation on adipogenesis and its underlying regulatory mechanisms. 3T3-F442A preadipocytes and primary preadipocytes isolated from wild type (WT) and CCR5 knockout (CCR5^-/-) mice were used to explore the role of CCR5 activation on adipocyte differentiation. To investigate the role of CCR5 on obesity in vivo, male C57BL/6J WT mice and CCR5^−/− mice were fed a normal chow (NC) or a high-fat diet (HFD) for 2 months, and plasma RANTES, the fat pad weight, adipocyte size of adipose tissues, and adipose CCR5 expression were measured. Results were showed that treatment with RANTES stimulated intracellular triglyceride accumulation and the expression of adipogenic transcription factors, such as PPARγ and C/EBPα, and adipocyte-specific protein a P 2 during the process of adipocyte differentiation. These findings suggested RANTES stimulated adipocyte differentiation. Pretreatment with CCR5 inhibitor maraviroc and ERK inhibitor PD98059 significantly inhibited RANTES-stimulated adipocyte differentiation. Besides, RANTES also stimulated adipocyte differentiation in the primary preadipocytes isolated from wild type mice but not CCR5 knockout (CCR5^-/-) mice. Furthermore, compared with NC feeding, elevated plasma RANTES level and adipose CCR5 expression, and obesity were observed in WT mice fed with HFD, but not CCR5^-/- mice. In conclusion, CCR5 activation by RANTES stimulated adipocyte differentiation via ERK-dependent pathway. CCR5 plays an important pathogenic role in the development of obesity.