dipocytes and immune cells are vital for the development of adipose tissue. Adipokines secreted by adipocytes regulate adipogenesis and body metabolism. Chemerin is one of the adipokines. However

the function and mechanism of chemerin in adipose tissue are not fully illuminated. Compared with wild type (WT) mice

Rarres2

−/−

mice gained weight and significantly increased fat distribution in subcutaneous adipose tissue (SAT)

rather than visceral adipose tissue (VAT) on high fat diet (HFD). PPARγ and C/EBPα

the master regulators of adipogenesis

were up-regulated in SAT and down-regulated in VAT in

Rarres2

−/−

mice comparing with WT mice. Inspite of chemerin deficiency or not

the ratio of adipocyte-progenitors to total cells and the differentiation capacity of adipocyte-progenitors were similar in SAT and VAT

but macrophage infiltration in VAT was more severe than in SAT in

Rarres2

−/−

mice. Furthermore

CD45

+

immune cells supernatant from

Rarres2

−/−

SAT promoted the differentiation of adipocyte-progenitors and 3T3-L1 cells. Adipokine array assay of CD45

+

immune cells supernatant revealed that metalloproteinase inhibitor 1 (TIMP1)

an inhibitor of adipogenesis

was reduced in

Rarres2

−/−

SAT

but increased in

Rarres2

−/−

VAT. As we specifically knocked down chemerin in SAT

TIMP1 was down-regulated and adipogenesis was promoted with reducing infiltration of macrophages. The present study demonstrates that the effects of chemerin on adipose tissue is depot different

and specific knock down chemerin in SAT promote adipogenesis and improve glucose tolerance test (GTT) and insulin tolerance test (ITT). This suggests a potential therapeutic target for chemerin in the treatment of obesity related metabolic disorder.