ESPE Abstracts

Background: Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through secreting hormones that regulate multiple functions at both organ and systemic levels

Objectives and Methods: We performed electronic literature systematic review using PubMed, Google Scholar, and Web of Sciences with the aim to provide an update on the link between adipocyte hormones and the immune system in infants and children during malnutrition. We reviewed 24 studies (2007-2022) fitting the search criteria. 

Results: Low leptin levels have been documented in all studies of children with malnutrition (mild, moderate, and severe). During fasting, leptin levels fall rapidly before and out of proportion to any changes in fat mass. The fall in serum leptin concentration leads to neurohumoral and behavioral changes. Evidence suggests that starvation hypo-leptinemia increases the activity of the hypothalamic-pituitary-adrenal axis, promoting lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. This function sustains the supply of energy substrates to the brain, heart, and other vital organs. In addition, leptin induces lymphopoiesis and seems to deliver survival signals to T cells. Leptin promotes IFN-γ secretion by memory T cells, inhibits Th2 responses, and induces activation markers (CD69, CD25, and CD71). Leptin enhances the activity of neutrophils by the release of oxygen free radicals and stimulates the migration of the immune through increasing intercellular adhesion molecule-1 (ICAM-1). Leptin activates the monocytes and dendrite cells (DCs) that lead to the production of pro-inflammatory cytokines such as TNF-α, and IL-6 along with IL-12. Leptin also promotes DCs survival by triggering the activation of nuclear factor-kappa B (NF-kappa B). Leptin deficiency in both mice and humans is characterized by a decrease in total lymphocytes, CD4+ helper T cell number, increased thymocyte apoptosis, and a shift from the Th1 toward Th2 phenotype. These changes increase susceptibility to intracellular infections and correlate with several bacterial, viral, and parasitic infections. In undernourished children, leptin level was the most reliable predictor of mortality. Adiponectin is reported to be low during malnutrition. Adiponectin improves insulin sensitivity and enhances lipid and glucose metabolism. It increases fatty acid oxidation in the liver and muscle. The anti-inflammatory properties of Adiponectin are due to its suppression of M1 macrophage activation and supporting M2 macrophage proliferation. It decreases inflammation, apoptosis, and oxidative injury in muscles, heart, and brain.

Conclusions: Low leptin and adiponectin can lead to impaired insulin secretion, decreased insulin sensitivity, encourage inflammation and increase oxidative tissue injury.