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Immunomodulatory actions of leptin

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Abstract

Leptin, the adipocyte-secreted hormone, exerts its main function as regulator of food intake and energy expenditure through central effects at the hypothalamic level. However, it appeared that this cytokine-like peptide has also direct effects on other peripheral tissues and cell types. Remarkable effects have been demonstrated on the immune function in vivo and in vitro. Monocytes are one of the target cells of leptin, and we have demonstrated that secretion of L-1Ra, an IL-1 receptor antagonist, is induced by leptin. In human obesity leptin and IL-1Ra levels are elevated, and these levels are decreased after weight loss. It is discussed that IL-1Ra may contribute to central leptin resistance.

Section snippets

Metabolic effects of leptin

Leptin, the product of the gene obese (ob), is a cytokine-like 16-kDa peptide produced by adipose tissue proportionally to the body fat mass (Campfield et al., 1995, Halaas et al., 1995, Zhang et al., 1994). The genetic defect in the leptin (ob) gene in mice results in overeating and reduced energy expenditure, leading to obesity, illustrating the important effects of leptin on maintaining energy balance (Coleman, 1978). Most, if not all, effects of leptin are mediated through the long form of

Evidence in vivo

Several in vivo studies have suggested a potential role for leptin in modulating the immune response (Table 1) (Fantuzzi and Faggioni, 2000). In human and rodents, nutritional deprivation affects both immune function (Chandra, 1991) and circulating leptin levels (Ahima et al., 1996, Grinspoon et al., 1996). Lymphoid atrophy is one of the consequences of prolonged fasting and since leptin levels are drastically reduced under such conditions, it was hypothesized that this adipocyte-derived factor

The immuno-metabolic signaling network

During the last few years it has become evident that leptin participates in functions other than the control of body weight and energy expenditure. A relation has emerged between leptin and inflammation, as evidenced by the altered immune response in genetically obese and starved rodents, as well as the available data on its effect on cytokines and hematopoiesis.

The marked upregulation of IL-1Ra by leptin is of particular interest, since it antagonize IL-1β, which was shown to mediate in part

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