title: Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals.
abstract: Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
authors.forename: Maria
authors.initials: M
authors.lastname: Dalamaga
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Kim
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: Ole-Petter
authors.initials: OP
authors.lastname: Hamnvik
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.forename: Jason
authors.initials: J
authors.lastname: Paruthi
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism* / Q000627:therapeutic use; D052497:Lipodystrophy, Congenital Generalized / Q000188:drug therapy / Q000378:metabolism; D054411:Receptors, Leptin / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin