TY - JOUR
T1 - Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals
AU - Moon, Hyun Seuk
AU - Dalamaga, Maria
AU - Kim, Sang Yong
AU - Polyzos, Stergios A.
AU - Hamnvik, Ole Petter
AU - Magkos, Faidon
AU - Paruthi, Jason
AU - Mantzoros, Christos S.
PY - 2013/6
Y1 - 2013/6
N2 - Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive,neuroendocrine,andimmunefunctions. Inthecontextofopen-labeluncontrolledstudies, 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.
AB - Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive,neuroendocrine,andimmunefunctions. Inthecontextofopen-labeluncontrolledstudies, 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.
UR - http://www.scopus.com/inward/record.url?scp=84878656502&partnerID=8YFLogxK
U2 - 10.1210/er.2012-1053
DO - 10.1210/er.2012-1053
M3 - Review article
C2 - 23475416
AN - SCOPUS:84878656502
SN - 0163-769X
VL - 34
SP - 377
EP - 412
JO - Endocrine Reviews
JF - Endocrine Reviews
IS - 3
ER -