Analysis of the effect of leptin on immune function in vivo using diet-induced obese mice

Abstract

Leptin can regulate several immune functions. However, the role of leptin on lymphocyte function has not been recognized in vivo. Accordingly, we have investigated the effect of leptin on starvation-induced immune dysfunction using diet-induced obese mice. To induce obesity, C57BL/6J mice were fed a high-fat diet for 14 weeks and control mice were fed a standard diet for the same period. The obese and control groups of mice were then starved for 48 h, and received intraperitoneal injections of recombinant leptin or phosphate-buffered saline four times during starvation. Other control mice in both diet groups were free fed without being starved. Although starvation of the control mice dramatically reduced the weights of the immune organs, cytokine production and increased proliferation of cultured splenocytes, these levels returned to those of the free-feeding groups with exogenous leptin administration. However, these effects of leptin were not observed in obese mice. These findings provide some evidence that leptin can regulate the immune function in vivo. It is also suggested that the action of leptin might not appear in obesity.

Leptin in Immunology

“…In vitro studies in diet-induced obese mice have shown that LPS stimulates proliferation of cultured splenocytes and that PHA stimulated production of certain cytokines (IFN-␥ and IL-10), but not all (IL-2) (80). In vivo studies in fasting diet-induced obese mice showed that leptin administration prevents pre-and poststarvation reduction in spleen weight compared with lean controls, but does not affect cytokine production (IL-2, IL-10, IFN-␥) in these mice, implying that the effect of leptin on immune cells in the obese state may be insignificant (81). Although our initial studies in humans (see above) are consistent with these findings in mice, it remains to be fully examined to which extent leptin influences the immune system and/or contributes to infections more frequently seen in patients with obesity.…”

The Inhibitory Role of α2,6-Sialylation in Adipogenesis

“…kines, which are bioactive molecules secreted from adipose tissue, are involved in energy metabolism, vascular homeostasis, and the immune response (1)(2)(3)(4)(5). Obesity results from excess accumulation of adipose tissue with hypertrophy and hyperplasia of adipocytes (5)(6)(7)(8)(9), which leads to abnormal secretion of adipocytokines (6,7) and triggers various diseases, including diabetes and cardiovascular diseases (2,6,7,10).…”

“…Obesity results from excess accumulation of adipose tissue with hypertrophy and hyperplasia of adipocytes (5)(6)(7)(8)(9), which leads to abnormal secretion of adipocytokines (6,7) and triggers various diseases, including diabetes and cardiovascular diseases (2,6,7,10). Although these morphofunctional modifications of adipocyte are related to cell adhesion molecules, such as integrins (11,12), the precise molecular mechanisms behind the adipocyte growth (referred to as adipogenesis) in obesity are not fully understood.…”

Influência do exercício sobre a resposta imunológica de ratos desnutridos.

“…O envolvimento desse hormônio sobre o sistema imunológico também é alvo de pesquisa recente (HOWARD et al, 1999;SAVINO, 2002;MITO et al, 2004;SCHAIBLE e KAUFFMANN, 2007). A hipótese de que em estado de desnutrição há um desequilíbrio na produção de leptina.…”

“…Outros estudos voltaram a sua atenção para o envolvimento desse hormônio com a regulação do sistema imunológico (HOWARD et al, 1999;SAVINO, 2002;MITO et al, 2004;SCHAIBLE e KAUFMANN, 2007). Hipotetiza-se que em estado de desnutrição há um desequilíbrio na produção de leptina, que seria responsável de proteger os órgãos linfóides (HOWARD et al, 1999;FANTUZZI e FAGGIONE, 2000;SAVINO, 2000;BLÜHER e MANTAZOROS, 2004).…”