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To the Editor:

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 stress-induced 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.

References

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  • 1
    Ma X, Hua J, Mohamood AR, Hamad AR, Ravi R, Li Z. A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury. HEPATOLOGY 2007; 46: 15191529.
  • 2
    Kremer M, Hines IN, Milton RJ, Wheeler MD. Favored T helper 1 response in a mouse model of hepatosteatosis is associated with enhanced T cell-mediated hepatitis. HEPATOLOGY 2006; 44: 216227.
  • 3
    La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol 2004; 4: 371379.
  • 4
    De Rosa V, Procaccini C, Cali G, Pirozzi G, Fontana S, Zappacosta S, et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity 2007; 26: 241255.
  • 5
    Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000; 62: 413437.
  • 6
    Chitturi S, Farrell G, Frost L, Kriketos A, Lin R, Fung C, et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? HEPATOLOGY 2002; 36: 403409.

Dechun Feng*, Feng Zhou†, Chuanfeng Wu*, * Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiaotong, University School of Medicine, Shanghai, China, † School of Life Science, China, Pharmaceutical University, Nanjing, China.