title: The Effects of Leptin Replacement on Neural Plasticity.
abstract: Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.
authors.affiliation: Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 2612, Australia.
authors.forename: Gilberto J
authors.initials: GJ
authors.lastname: Paz-Filho
mesh_terms: D000568:Amenorrhea / Q000188:drug therapy; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D020738:Leptin / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D008060:Lipodystrophy / Q000188:drug therapy; D008297:Male; D009154:Mutation; D009473:Neuronal Plasticity; D016896:Treatment Outcome
chemical_list: D020738:Leptin; C415771:metreleptin