In vivo modulation of Hmgic reduces obesity

The HMGI family of proteins consists of three members(1,2), HMGIC, HMGI and HMGI(Y), that function as architectural factors(3-5) 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(10-12), including fat-cell tumours(12) (lipomas), In addition Hmgic(-/-) mice have a deficiency in fat tissue(13), 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.