title: Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice.
abstract: Leptin is an adipose-derived hormone that signals to inform the brain of nutrient status; loss of leptin signaling results in marked hyperphagia and obesity. Recent work has identified several groups of neurons that contribute to the effects of leptin to regulate energy balance, but leptin receptors are distributed throughout the brain, and the function of leptin signaling in discrete neuronal populations outside of the hypothalamus has not been defined. In the current study, we produced mice in which the long form of the leptin receptor (Lepr) was selectively ablated using Cre-recombinase selectively expressed in the hindbrain under control of the paired-like homeobox 2b (Phox2b) promoter (Phox2b Cre Lepr(flox/flox) mice). In these mice, Lepr was deleted from glucagon-like 1 peptide-expressing neurons resident in the nucleus of the solitary tract. Phox2b Cre Lepr(flox/flox) mice were hyperphagic, displayed increased food intake after fasting, and gained weight at a faster rate than wild-type controls. Paradoxically, Phox2b Cre Lepr(flox/flox) mice also exhibited an increased metabolic rate independent of a change in locomotor activity that was dependent on food intake, and glucose homeostasis was normal. Together, these data support a physiologically important role of direct leptin action in the hindbrain.
authors: Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9077, USA.
authors: Michael M
authors: MM
authors: Scott
authors: Kevin W
authors: KW
authors: Williams
authors: Jari
authors: J
authors: Rossi
authors: Charlotte E
authors: CE
authors: Lee
authors: Joel K
authors: JK
authors: Elmquist
references: Mol Cell Neurosci. 2000 Mar;15(3):235-43
references: 10736201
references: Cell Metab. 2010 Jan;11(1):77-83
references: 20074530
references: Endocrinology. 2002 Jan;143(1):239-46
references: 11751615
references: Neuron. 2006 Jan 19;49(2):191-203
references: 16423694
references: Endocrinology. 2009 Apr;150(4):1705-11
references: 19056818
references: Neuron. 2004 Jun 24;42(6):983-91
references: 15207242
references: Endocrinology. 2008 May;149(5):2138-48
references: 18258679
references: Endocrinology. 2009 Dec;150(12):5326-33
references: 19819963
references: Front Neuroendocrinol. 2010 Jan;31(1):61-78
references: 19836413
references: Development. 1997 Oct;124(20):4065-75
references: 9374403
references: J Neurosci. 2006 Oct 4;26(40):10305-14
references: 17021186
references: J Comp Neurol. 2000 Jul 24;423(2):261-81
references: 10867658
references: Int J Obes (Lond). 2009 Apr;33 Suppl 1:S11-5
references: 19363500
references: Endocrinology. 2007 May;148(5):2189-97
references: 17317774
references: Cell. 1995 Dec 29;83(7):1263-71
references: 8548812
references: Development. 2003 Dec;130(26):6635-42
references: 14627719
references: J Neurosci. 2010 Feb 17;30(7):2472-9
references: 20164331
references: Neuroscience. 2002;109(2):339-47
references: 11801369
references: Regul Pept. 1998 Sep 25;75-76:271-8
references: 9802419
references: Peptides. 1988 Mar-Apr;9(2):221-5
references: 3375133
references: Cell Metab. 2005 Jan;1(1):63-72
references: 16054045
references: J Clin Invest. 2005 Mar;115(3):703-10
references: 15711637
references: Brain Res. 2007 May 29;1149:118-26
references: 17433266
references: Physiol Behav. 2001 Jan;72(1-2):123-8
references: 11239989
references: Endocrinology. 2007 Apr;148(4):1868-81
references: 17194747
references: J Comp Neurol. 2009 Jun 10;514(5):518-32
references: 19350671
references: Neuron. 1999 Apr;22(4):693-705
references: 10230790
references: Science. 1995 Jul 28;269(5223):543-6
references: 7624777
references: Cell Metab. 2011 Feb 2;13(2):195-204
references: 21284986
references: Nature. 1998 Oct 22;395(6704):763-70
references: 9796811
references: J Clin Invest. 2001 Oct;108(8):1113-21
references: 11602618
references: Endocrinology. 1997 Feb;138(2):839-42
references: 9003024
references: Endocrinology. 2008 Feb;149(2):492-7
references: 17974623
references: Diabetes. 2010 Feb;59(2):323-9
references: 20103710
references: Nature. 1994 Dec 1;372(6505):425-32
references: 7984236
references: Nature. 1997 Jun 26;387(6636):903-8
references: 9202122
references: Biol Psychiatry. 2010 Jun 1;67(11):1075-82
references: 20060958
references: Endocrinology. 2003 May;144(5):2016-24
references: 12697710
references: J Physiol. 2006 Jun 1;573(Pt 2):395-412
references: 16581866
references: Nature. 1999 May 27;399(6734):366-70
references: 10360575
references: Endocrinology. 2002 Oct;143(10):3779-84
references: 12239088