Leptin, a possible cause for regulatory T cell loss in fatty liver?

Abstract

We read with interest the article by Ma et al. on how a high-fat diet reduced regulatory T cells (Tregs) in liver and influenced susceptibility to endotoxin-induced liver injury.1 This interesting finding may also explain a previous report on increased sensitivity in mice with fatty liver to concanavalin A–induced hepatitis.2 The authors attributed the mechanism of Treg loss to oxidative stressinduced apoptosis. Recently, several agents were found that regulate Treg survival and function. Among them, leptin, a neuroendocrine and immune mediator,3 acts as a negative signal for the proliferation of Tregs.4 The suppressive effect of leptin on Tregs was mediated by the modulation of cyclin-dependent kinase inhibitor p27 (p27kip1) levels and phosphorylation of extracellular-related kinase 1 (ERK1) and ERK2. Serum leptin levels can be considered as a signal to the body of its energy reserves.5 Previous studies have clearly shown that serum leptin levels correlate directly with the severity of hepatic steatosis.6 Therefore, based on these findings, it will be interesting and important to verify the role elevated leptin levels play in Treg loss in mice with fatty livers. In addition, a significant increase of the percentage of peripheral Tregs was observed in mice with a genetic deficiency of leptin (ob/ob mice).4 One of the most prominent phenotypes of ob/ob mice was fatty liver. So, further research should be carried out to determine the percentage of Tregs in liver of ob/ob mice. These studies will improve our knowledge about the interaction between hepatocytes and immune cells in the liver.