Adipocyte hyperplasia and RMI1 in the treatment of obesity

Obesity is a complex disorder and a major risk factorfor metabolic diseases such as type 2 diabetes mellitus,hypertension and cardiovascular disease. Obesity devel-ops as the result of an imbalance between energyintake and expenditure. To state simply, chronic reduc-tion of energy expenditure versus intake causes anincreased storage of the excess energy in the form ofintracellular triacylglycerol droplets in adipose cells,leading to an increased fat mass and ultimately result-ing in obesity.Adipocyte hyperplasia (increase in cell number) andhypertrophy (increase in cell size) are thought to bedirectly responsible for the observed increase in adi-pose tissue mass [1,2]. Adipocyte hypertrophy in par-ticular is considered the main cause of adult obesity,and hyperplasia of adipocytes in obese adults some-times occurs secondary to adipocyte hypertrophy, pos-sibly due to an increased number of adipocytescapable of secreting paracrine growth factors thatinduce adipocyte hyperplasia [3].Whereas the basic number of adipocytes is estab-lished during childhood and adolescence in bothhumans and rodents, adipose tissue retains the abilityto generate new adipocytes throughout life. Increasedadipocyte number during aging has been implicated inthe rising incidence and severity of obesity among theelderly [4]. Thiazolidinediones, a class of oral antidia-betic agents, are nuclear receptor peroxisome prolifera-tor-activated receptor gamma agonists which enhancegeneration of small-sized adipocytes by inducing adi-