@article{88f012e31dd04832ac60155c9e039f10,
title = "Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility",
abstract = "Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. However, the physiological significance of concomitant leptin and insulin action on POMC neurons remains to be established. Here, we show that mice lacking both leptin and insulin receptors in POMC neurons (Pomc-Cre, Leprflox/flox IRflox/flox mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, Leprflox/flox IRflox/flox female mice display elevated serum testosterone levels and ovarian abnormalities, resulting in reduced fertility. We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function.",
keywords = "HUMDISEASE",
author = "Hill, {Jennifer W.} and Elias, {Carol F.} and Makoto Fukuda and Williams, {Kevin W.} and Berglund, {Eric D.} and Holland, {William L.} and Cho, {You Ree} and Chuang, {Jen Chieh} and Yong Xu and Michelle Choi and Danielle Lauzon and Lee, {Charlotte E.} and Roberto Coppari and Richardson, {James A.} and Zigman, {Jeffrey M.} and Streamson Chua and Scherer, {Philipp E.} and Lowell, {Bradford B.} and Br{\"u}ning, {Jens C.} and Elmquist, {Joel K.}",
note = "Funding Information: The authors gratefully acknowledge Jason Anderson for technical assistance; Aktar Ali, Laura Brule, and Damalie Namponye for Metabolic Phenotyping Core support (supported by NIH grants 1PL1DK081182 and 1UL1RR024923); and S.R. Hammes and R.E. Hammer for interpretive assistance. Ovarian histology was provided by the UTSW Molecular Pathology Core Laboratory and the University of Toledo Advanced Microscopy & Imaging Center Facility (supported by the Cancer Biology Fund of the University of Toledo Foundation). Radioimmunoassays were performed by A.F. Parlow (Harbor-UCLA REI) and Aleisha Schoenfelder (UVA Ligand Assay and Analysis Core; NICHD/NIH [SCCPRI] Grant U54-HD28934). This work was supported by German research foundation (DFG1492-7/1) funding to J.C.B.; American Diabetes Association and a Smith Family Foundation Pinnacle Program Project Award to J.K.E.; and NIH grants 1F32DK066972 and K99HD056491 to J.W.H., PO1 DK56116 to B.B.L. and J.K.E., and R01DK53301 and RL1DK081185 to J.K.E. TL1DK081181 supported E.D.B. ",
year = "2010",
month = apr,
day = "7",
doi = "10.1016/j.cmet.2010.03.002",
language = "English (US)",
volume = "11",
pages = "286--297",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}