Leptin regulates energetic tradeoffs between body fat and humoural immunity

Abstract

Mounting an immune response requires a relatively substantial investment of energy and marked reductions in energy availability can suppress immune function and presumably increase disease susceptibility. We have previously demonstrated that a moderate reduction in energy stores via partial surgical lipectomy (LIPx) impairs humoural immunity of Siberian hamsters (Phodopus sungorus). Here we tested the hypothesis that LIPx-induced decreases in immunity are mediated by changes in the adipose tissue hormone leptin. Hamsters received bilateral surgical removal of inguinal white adipose tissue (IWATx) or sham surgeries (Sham). Half the animals in each group received osmotic minipumps containing murine leptin (0.5mulh-1 for 10 days) whereas the remaining animals received minipumps containing vehicle alone; all animals were subsequently challenged with the novel antigen keyhole limpet haemocyanin (KLH). In general, serum leptin and anti-KLH antibodies were significantly correlated with one another with higher levels generally indicating enhanced immunity. In addition, IWATx hamsters had significantly lower serum anti-KLH IgG compared with sham animals. Exogenous leptin, however, attenuated LIPx-induced immune suppression but did not affect humoural immunity in sham animals. These results suggest that reductions in energy availability lead to impairments in humoural immunity and that leptin can serve as a neuroendocrine signal between body fat and immunity regulating humoural immune responses.

Figure 1

Mean (±s.e.m.) serum leptin concentrations in Siberian hamsters receiving bilateral IWAT lipectomies (IWATx), or sham surgeries (sham) and treated with exogenous leptin or vehicle alone. Significant differences between pair-wise means are indicated by an asterisk if p<0.05.

Figure 2

Mean (±s.e.m.) serum anti-KLH immunoglobulin G (IgG) levels in Siberian hamsters receiving bilateral IWAT lipectomies (IWATx), or sham surgeries (sham) and treated with exogenous leptin or vehicle alone. Groups with different numbers indicate statistically significant differences between groups means (p<0.05); groups sharing the same number are statistically equivalent.

Figure 3

Relationship between serum leptin (ng ml⁻¹) and anti-KLH concentrations (% plate positive) of Siberian hamsters (p<0.05).

Figure 4

Mean (±s.e.m.) (a) body masses and (b) white adipose tissue pad masses [epididymal (EWAT), inguinal (IWAT) and retroperotoneal (RWAT)] in Siberian hamsters receiving bilateral IWAT lipectomies (IWATx), or sham surgeries (sham) and treated with exogenous leptin or vehicle alone.