@article{f45063728ec246a39683c5775685fa86,
title = "Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis",
abstract = "Melanocortin-4 receptor (MC4R) mutations cause dysregulation of energy balance and hyperinsulinemia. We have used mouse models to study the physiological roles of extrahypothalamic MC4Rs. Re-expression of MC4Rs in cholinergic neurons (ChAT-Cre, loxTB MC4R mice) modestly reduced body weight gain without altering food intake and was sufficient to normalize energy expenditure and attenuate hyperglycemia and hyperinsulinemia. In contrast, restoration of MC4R expression in brainstem neurons including those in the dorsal motor nucleus of the vagus (Phox2b-Cre, loxTB MC4R mice) was sufficient to attenuate hyperinsulinemia, while the hyperglycemia and energy balance were not normalized. Additionally, hepatic insulin action and insulin-mediated suppression of hepatic glucose production were improved in ChAT-Cre, loxTB MC4R mice. These findings suggest that MC4Rs expressed by cholinergic neurons regulate energy expenditure and hepatic glucose production. Our results also provide further evidence of the dissociation in pathways mediating the effects of melanocortins on energy balance and glucose homeostasis.",
author = "Jari Rossi and Nina Balthasar and David Olson and Michael Scott and Eric Berglund and Lee, {Charlotte E.} and Choi, {Michelle J.} and Danielle Lauzon and Lowell, {Bradford B.} and Elmquist, {Joel K.}",
note = "Funding Information: We would like to thank the Mouse Metabolic Phenotyping Cores at University of Texas Southwestern Medical Center at Dallas (supported by PL1 DK081182-01 and UL1RR024923) and Beth Israel Deaconess Transgenic Core (supported by BNORC P30 DK46200 and BADERC P30 DK057521). We thank Dr. Jen-Chieh Chuang for providing technical advice in total pancreatic insulin measurements, Dr. Liz Robertson for providing the IRES-Cre fusion plasmid, and Dr. Laurent Gautron for the discussion of our work. This work was supported by grants to J.R. (Sigrid Jus{\'e}lius Foundation, Academy of Finland, and Finnish Cultural Foundation), N.B. (British Heart Foundation Intermediate Fellowship FS/06/057, ADA-EASD Transatlantic Fellowship, BONRC P30DK046200), D.O. (K08DK071561), M.S. (K99DK024719-02), E.B. (TORS-Interdisciplinary Research Training Program 5TL1DK081181), B.B.L. (RO1DK075632), and J.K.E. (R01DK53301, DK071320, and RL1DK081185) and support from the American Diabetes Association and a Smith Family Foundation Pinnacle Program Project Award. ",
year = "2011",
month = feb,
day = "2",
doi = "10.1016/j.cmet.2011.01.010",
language = "English (US)",
volume = "13",
pages = "195--204",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",
}