Glitazones for human nonalcoholic steatohepatitis

Abstract

The rationale for specific pharmacologic therapy in nonalcoholic steatohepatitis (NASH) is determined by the potential for disease progression and the difficulties, in many patients, of successfully implementing diet and lifestyle changes over the long term. Owing to their ability to correct insulin resistance, insulin-sensitizing agents are attractive candidates for the treatment of NASH. In this review we provide an insight into the mechanism of action, therapeutic efficacy and safety issues regarding the use of glitazones in NASH.

Keywords: fibrosis; glitazones; insulin resistance; insulin sensitizing drugs; nonalcoholic steatohepatitis; steatosis.

Figure 1.

Mechanism of action of glitazones. Glitazones promote the differentiation of small, metabolically active, insulin-sensitive (IS) adipocytes from large, insulin-resistant (IR) adipocytes. This results in decreased free fatty acids (FFA) influx to the liver, decreased tumor necrosis factor alpha (TNFα) expression, increased adiponectin production and redistribution of fat mass. The consequence is an increase in the storage of fatty acids in adipose tissue, a reduction of hepatic glucose production and a higher uptake of the glucose in the muscles which results in enhanced insulin sensitivity.