May be involved in the regulation of the inflammatory network. The role as pro- or anti-inflammatory seems to be context dependent (By similarity). Seems to have some role in regulating food intake and energy balance when administered in the brain. This effect is sustained over a two-day period, and it is accompanied by decreased expression of orexigenic neuropeptides in the hypothalamus 3 hours post-injection (Probable). Homomultimer. Forms trimers, hexamers and high molecular weight oligomers. High expression in testis, kidney, and brain. Expressed in brain and kidney (at protein level). Within the brain, highly expressed in cerebellum, cortex, hippocampus and hippothalamus, and lower expression in hindbrain (at protein level). Serum levels were increased in leptin-deficient ob/ob mice (a genetic model of hyperphagia and morbid obesity) relative to age-matched lean controls. No difference in serum levels were detected between mice fed a low-fat versus high-fat diet for 14 weeks (PubMed:24366864). Up-regulated during acute colitis induced by injection of dextran sulfate sodium (DSS). There are conflicting results in its involvement in the inflammatory network. It was first described to be a pro-inflammatory cytokine by inducing the activation of NF-kappa-B signaling pathway and up-regulates IL6 production in liver carcinoma cells. While it seems to have the opposite effect in macrophages. Involvement in food intake and energy was only observed when the protein was externally administered in the brain, but not when this protein was overexpressed in vivo (PubMed:24366864).