Altered response to metabolic challenges in mice with genetically targeted deletions of galanin-like peptide.
Galanin-like peptide (GALP) is expressed in the arcuate nucleus and is implicated in the neuroendocrine regulation of metabolism and reproduction. To investigate the physiological significance of GALP, we generated and characterized a strain of mice with a genetically targeted deletion in the GALP gene [GALP knockout (KO) mice]. We report that GALP KO mice have a subtle, but notable, metabolic phenotype that becomes apparent during adaptation to changes in nutrition. GALP KO mice are indistinguishable from wild-type (WT) controls in virtually all aspects of growth, sexual development, body weight, food and water consumption, and motor behaviors, when they are allowed unlimited access to standard rodent chow. However, GALP KO mice have an altered response to changes in diet. 1) Male GALP KO mice consumed less food during refeeding after a fast than WT controls (P < 0.01). 2) GALP KO mice of both sexes gained less weight on a high-fat diet than WT controls (P < 0.01), despite both genotypes having consumed equal amounts of food. We conclude that although GALP signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, GALP may play a role in readjusting energy balance under changing nutritional circumstances.
Dungan Lemko
Heather M
HM
Dept. of Obstetrics & Gynecology, Univ. of Washington, Seattle, WA 98195-6460, USA.
Clifton
Donald K
DK
Steiner
Robert A
RA
Fraley
Gregory S
GS
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D004326:Drinking / Q000235:genetics / Q000502:physiology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology; D044089:Galanin-Like Peptide / Q000235:genetics* / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D017403:In Situ Hybridization; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008660:Metabolism / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000378:metabolism; D010053:Ovary / Q000254:growth & development / Q000502:physiology; D010641:Phenotype; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D012741:Sexual Maturation / Q000235:genetics / Q000502:physiology; D013737:Testis / Q000254:growth & development / Q000502:physiology; D015430:Weight Gain / Q000502:physiology
D000963:Antimetabolites; D004041:Dietary Fats; D044089:Galanin-Like Peptide; D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin; D007986:Luteinizing Hormone; D003847:Deoxyglucose; D005947:Glucose
Diabetes. 2007 Apr;56(4):1051-8
17251274
Endocrinology. 2001 Apr;142(4):1626-34
11250944
Science. 2005 Oct 28;310(5748):683-5
16254186
Neuroendocrinology. 2001 Jan;73(1):2-11
11174012
Neurosci Lett. 2007 May 29;419(2):125-30
17485169
Endocrinology. 2003 Jun;144(6):2634-43
12746327
Regul Pept. 2000 Aug 25;92(1-3):51-6
11024565
J Neuroendocrinol. 2004 Apr;16(4):378-82
15089978
Neuroreport. 2005 Feb 28;16(3):243-7
15706228
Mol Cell Biol. 2004 Apr;24(7):2978-85
15024085
Endocrinology. 1997 Oct;138(10):4489-92
9322969
Endocrinology. 2001 Dec;142(12):5140-4
11713207
J Clin Endocrinol Metab. 2004 Apr;89(4):1760-6
15070942
Biol Reprod. 1999 Feb;60(2):216-22
9915984
Endocrinology. 2003 Apr;144(4):1143-6
12639894
Endocrinology. 2002 Mar;143(3):755-63
11861493
Neuroendocrinology. 2004;79(5):268-77
15249737
Endocrinology. 2003 Mar;144(3):813-22
12586757
J Neuroendocrinol. 2004 Aug;16(8):717-23
15271065
Physiol Behav. 2007 Dec 5;92(5):814-23
17632189
Trends Endocrinol Metab. 2004 Jul;15(5):215-21
15223051
Physiol Behav. 2001 Nov-Dec;74(4-5):683-701
11790431
Endocrinology. 2003 Nov;144(11):4709-17
12960003
J Biol Chem. 1999 Dec 24;274(52):37041-5
10601261
J Clin Invest. 2005 Dec;115(12):3573-8
16322795
Diabetes. 2005 Aug;54(8):2471-6
16046316
Anat Rec. 1976 Oct;186(2):185-205
984473
Endocrinology. 2004 Oct;145(10):4565-74
15242985
J Clin Invest. 2005 Dec;115(12):3564-72
16322794
J Neuroendocrinol. 2004 Jan;16(1):10-8
14962070
Horm Behav. 2005 Aug;48(2):141-51
16042964
J Neuroendocrinol. 2008 Jan;20(1):128-37
18081561
Endocrinology. 2000 Jul;141(7):2703-6
10875277
Neuroendocrinology. 2004;79(6):327-37
15256810
Diabetes. 2004 May;53(5):1237-42
15111492
Neuroendocrinology. 2006;83(2):97-105
16825797
Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1281-9
16849629