title: Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity.
abstract: Obesity is associated with a decrease in energy expenditure relative to energy intake. The decrease in physical activity associated with obesity in several species, including humans, contributes to decreased energy expenditure. Several hormones and neuropeptides that affect appetite also modulate physical activity, including neuromedin U (NMU), a peptide found in the gut and brain. We have demonstrated that NMU microinjected into the hypothalamic paraventricular nucleus (PVN) in rats increases the energy expenditure associated with physical activity, called non-exercise activity thermogenesis (NEAT). Here we examined whether obesity in rats is related to decreased sensitivity of the PVN to the locomotor-activating effect of NMU. Diet-induced obese (DIO) rats and lean, diet-resistant (DR) rats were given PVN microinjections of increasing doses of NMU both before and after 1 month on a high-fat diet. We found that NMU increases physical activity, energy expenditure, and NEAT in a dose-dependent manner in both DR and DIO rats, both before and after 1 month on the high-fat diet. Before high-fat feeding, the obesity-prone and lean rats showed similar levels of physical activity after intra-PVN microinjections of NMU. After 1 month of the high-fat diet, however, the obesity-resistant rats showed significantly more NMU-induced physical activity compared to the obese DIO rats. Taken together with previous studies, these results suggest that obesity may represent a state associated with decreased central sensitivity to neuropeptides such as NMU that increase physical activity and therefore energy expenditure.
authors: Mayo Clinic, Endocrine Research Unit, St Marys Hospital, Joseph 5-194, 200 1st St. SW, Rochester, MN 55905, USA. novak.colleen@mayo.edu
authors: Colleen M
authors: CM
authors: Novak
authors: Minzhi
authors: M
authors: Zhang
authors: James A
authors: JA
authors: Levine
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005526:Food, Formulated; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D022722:Thermogenesis / Q000187:drug effects / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D009479:Neuropeptides; C056900:neuromedin U
references: Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1110-5
references: 15475504
references: Science. 2005 May 13;308(5724):1043-5
references: 15845877
references: J Comp Neurol. 2001 May 7;433(3):312-34
references: 11298358
references: Am J Physiol Regul Integr Comp Physiol. 2000 Jan;278(1):R231-7
references: 10644644
references: Arch Pediatr Adolesc Med. 2003 Sep;157(9):882-6
references: 12963593
references: Am J Physiol Regul Integr Comp Physiol. 2005 Apr;288(4):R981-6
references: 15604298
references: Am J Physiol. 1999 Jun;276(6):R1569-78
references: 10362733
references: J Neurosci. 1986 Oct;6(10):2908-14
references: 3020187
references: Adv Data. 2004 Oct 27;(347):1-17
references: 15544194
references: Am J Physiol Regul Integr Comp Physiol. 2002 Oct;283(4):R941-8
references: 12228064
references: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9888-93
references: 17517647
references: Am J Physiol Endocrinol Metab. 2001 Oct;281(4):E670-5
references: 11551842
references: Jpn J Physiol. 1998 Jun;48(3):211-4
references: 9689151
references: Endocrinology. 2002 Nov;143(11):4227-34
references: 12399416
references: J Biol Rhythms. 1999 Oct;14(5):364-77
references: 10511004
references: JAMA. 2002 Oct 9;288(14):1723-7
references: 12365955
references: Nat Neurosci. 2005 May;8(5):579-84
references: 15856066
references: Endocrinology. 2002 Oct;143(10):3813-21
references: 12239092
references: Am J Med. 1997 Mar;102(3):259-64
references: 9217594
references: Anim Behav. 1998 Jul;56(1):11-27
references: 9710457
references: Nature. 2000 Jul 6;406(6791):70-4
references: 10894543
references: Nature. 1998 May 7;393(6680):72-6
references: 9590691
references: Am J Physiol Regul Integr Comp Physiol. 2003 Jun;284(6):R1454-65
references: 12560202
references: Prog Brain Res. 1996;111:241-52
references: 8990919
references: J Neurosci Methods. 2005 Aug 15;146(2):191-7
references: 16054509
references: J Nutr. 2005 May;135(5):1314-9
references: 15867332
references: Am J Physiol Endocrinol Metab. 2006 Feb;290(2):E396-403
references: 16188908
references: Am J Physiol. 1998 Aug;275(2):R478-84
references: 9688683
references: Med Sci Sports Exerc. 2004 May;36(5):890-6
references: 15126726
references: Am J Med. 1998 Aug;105(2):145-50
references: 9727822
references: N Engl J Med. 2004 Dec 23;351(26):2694-703
references: 15616204
references: Med Sci Sports Exerc. 2005 May;37(5):724-30
references: 15870624
references: J Clin Endocrinol Metab. 2006 Dec;91(12):5057-63
references: 16984985
references: Biochem Biophys Res Commun. 2000 Mar 5;269(1):41-5
references: 10694474
references: J Neurosci. 1999 Jan 1;19(1):328-33
references: 9870962
references: Science. 2005 Jan 28;307(5709):584-6
references: 15681386
references: Neurosci Lett. 2005 Jul 22-29;383(1-2):99-104
references: 15936519
references: Am J Physiol. 1986 Sep;251(3 Pt 2):R433-40
references: 3529988
references: Am J Physiol. 1989 Mar;256(3 Pt 2):R766-71
references: 2646957
references: Physiol Behav. 2003 Nov;80(2-3):273-9
references: 14637226
references: J Biol Rhythms. 2004 Feb;19(1):58-67
references: 14964704
references: Regul Pept. 2000 Aug 25;92(1-3):31-5
references: 11024562
references: Biochem Biophys Res Commun. 2004 Oct 8;323(1):65-71
references: 15351702
references: Physiol Behav. 2006 Jun 30;88(3):294-301
references: 16787655
references: Psychopharmacology (Berl). 2004 Dec;177(1-2):1-14
references: 15205870
references: Am J Physiol. 1998 Aug;275(2):R471-7
references: 9688682
references: Arch Gerontol Geriatr. 2004 Jul-Aug;39(1):83-91
references: 15158583
references: Biochem Biophys Res Commun. 2001 Nov 23;289(1):225-8
references: 11708803
references: Endocrinology. 2005 Oct;146(10):4217-23
references: 15976061
references: J Nutr. 1991 Jul;121(7):1075-80
references: 2051227
references: Peptides. 2004 Mar;25(3):473-504
references: 15134868
references: Am J Physiol Regul Integr Comp Physiol. 2002 Feb;282(2):R546-51
references: 11792665
references: Obes Res. 2001 Nov;9 Suppl 4:228S-233S
references: 11707546
references: J Biol Chem. 2000 Dec 15;275(50):39482-6
references: 11010960
references: Am J Physiol Regul Integr Comp Physiol. 2004 Jan;286(1):R143-50
references: 12958061
references: Am J Physiol Endocrinol Metab. 2004 Apr;286(4):E551-9
references: 14656716
references: Brain Res Gene Expr Patterns. 2001 Aug;1(1):1-4
references: 15018811
references: Endocrinology. 2004 Aug;145(8):3904-12
references: 15117877
references: Stress. 2004 Jun;7(2):109-12
references: 15512854
references: Nat Med. 2004 Oct;10(10):1067-73
references: 15448684
references: Int J Obes (Lond). 2006 Sep;30(9):1322-31
references: 16801931
references: Endocrinology. 2004 Oct;145(10):4645-52
references: 15231700
references: Neuroscience. 1988 Jun;25(3):797-816
references: 3405430
references: J Neuroendocrinol. 2004 Jul;16(7):612-9
references: 15214864
references: Am J Physiol Endocrinol Metab. 2005 Aug;289(2):E301-5
references: 16014357
references: Am J Physiol. 1996 Feb;270(2 Pt 2):R456-61
references: 8779879
references: Physiol Behav. 1991 Sep;50(3):573-81
references: 1801012
references: Int J Obes (Lond). 2006 May;30(5):782-6
references: 16404406
references: Can J Physiol Pharmacol. 1990 Jan;68(1):17-27
references: 2183917
references: Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1184-91
references: 12855420
references: J Neurochem. 2003 Dec;87(5):1165-73
references: 14622096
references: Behav Processes. 2005 Feb 28;68(2):165-72
references: 15686826
references: Science. 1999 Jan 8;283(5399):212-4
references: 9880251
references: J Biol Chem. 2000 Oct 20;275(42):32452-9
references: 10899166
references: J Neurophysiol. 2003 Aug;90(2):843-50
references: 12711715
references: Am J Physiol. 1997 Aug;273(2 Pt 2):R725-30
references: 9277561
references: Neuroendocrinology. 1990 Nov;52(5):441-7
references: 2177853
references: EMBO J. 2005 Jan 26;24(2):325-35
references: 15635449
references: Am J Physiol Regul Integr Comp Physiol. 2005 Sep;289(3):R704-11
references: 15879056
references: Am J Clin Nutr. 2003 Aug;78(2):209-14
references: 12885699
references: J Neuroendocrinol. 2006 Aug;18(8):594-601
references: 16867180
references: Endocrinology. 2002 Nov;143(11):4320-9
references: 12399428
references: Neurosci Lett. 2005 Feb 1;374(1):69-72
references: 15631899
references: Endocrine. 2001 Dec;16(3):201-6
references: 11954664
references: Biochem Biophys Res Commun. 2004 May 21;318(1):156-61
references: 15110767
references: J Endocrinol. 2005 Apr;185(1):151-64
references: 15817836
references: JAMA. 2003 Apr 9;289(14):1785-91
references: 12684356
references: Eur J Clin Nutr. 1991 Sep;45(9):419-30
references: 1959514
references: Curr Opin Clin Nutr Metab Care. 2004 Nov;7(6):599-605
references: 15534426
references: Behav Brain Res. 2004 Oct 5;154(2):511-7
references: 15313040
references: Am J Physiol Regul Integr Comp Physiol. 2000 Oct;279(4):R1357-64
references: 11004005
references: Nature. 1982 May 27;297(5864):331-3
references: 6978997
references: Biochem Biophys Res Commun. 2003 Nov 28;311(4):954-8
references: 14623274
references: Endocrinology. 1988 Jan;122(1):270-82
references: 3335208
references: J Clin Invest. 1995 Mar;95(3):980-5
references: 7883999
references: Biochem Biophys Res Commun. 2000 Oct 14;277(1):191-4
references: 11027662
references: Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R889-99
references: 16763079
references: Physiol Behav. 2002 Nov;77(2-3):251-7
references: 12419401