Leptin regulates proinflammatory immune responses

TLDR

Obesity increases infection, diabetes, and cardiovascular disease risk, and leptin deficiency contributes to obesity while abnormal TNF‑α expression in these comorbidities suggests leptin may regulate immune responses. The study aimed to determine whether impaired leptin signaling directly promotes the complications associated with obesity. Rodent models with leptin or receptor mutations showed reduced macrophage phagocytosis and proinflammatory cytokine production, whereas exogenous leptin restored these functions, revealing leptin as a key up‑regulator of inflammatory immunity that may underlie obesity‑related complications.

Abstract

Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.