In vivo modulation of Hmgic reduces obesity

Abstract

The HMGI family of proteins consists of three members^1,2, HMGIC, HMGI and HMGI(Y), that function as architectural factors^3,4,5 and are essential components of the enhancesome^6,7. HMGIC is predominantly expressed in proliferating, undifferentiated mesenchymal cells and is not detected in adult tissues^8,9. It is disrupted and misexpressed in a number of mesenchymal tumour cell types^10,11,12, including fat-cell tumours¹² (lipomas). In addition Hmgic^–/– mice have a deficiency in fat tissue¹³. To study its role in adipogenesis and obesity, we examined Hmgic expression in the adipose tissue of adult, obese mice. Mice with a partial or complete deficiency of Hmgic resisted diet-induced obesity. Disruption of Hmgic caused a reduction in the obesity induced by leptin deficiency (Lep^ob/Lep^ob) in a gene-dose–dependent manner. Our studies implicate a role for HMGIC in fat-cell proliferation, indicating that it may be an adipose-specific target for the treatment of obesity.