We appreciate the comment of Feng and colleagues regarding the effects of leptin on regulatory T cells (Tregs). We also believe that the hepatic Treg depletion in nonalcoholic fatty liver disease (NAFLD) is likely multifactorial, including increased oxidative stress and elevated leptin levels. A recent study shows that leptin suppresses proliferation of Tregs.1 Leptin-deficient ob/ob mice have increased number of Tregs in peripheral1 and lymphoid organs.2 However, ob/ob mouse may not be an ideal model to study the role of Tregs in NAFLD. The number of Tregs in the liver of ob/ob mice is the result of the combined effects of increased oxidative stress (which increases Treg apoptosis) and leptin deficiency (which increases Treg proliferation). Our results in a study with similar hepatic Treg proliferation in diet-induced steatosis indicated little impact of increased leptin on Treg proliferation.3 In fact, our preliminary results indicated there was no significant difference in the number of hepatic Tregs between ob/ob mice and their lean littermates (unpublished data). Unlike obese humans with elevated leptin levels, absence of leptin in ob/ob mice has a significant immunoregulatory response, as mentioned above. Mice with diet-induced obesity and NAFLD resemble the human model of metabolic syndrome.


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  • 1
    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.
  • 2
    Matarese G, Carrieri PB, La Cava A, Perna F, Sanna V, De Rosa V, et al. Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci U S A 2005; 102: 51505155.
  • 3
    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.

Zhiping Li M.D.*, * Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD.