title: Pro-opiomelanocortin modulates the thermogenic and physical activity responses to high-fat feeding and markedly influences dietary fat preference.
abstract: Complete proopiomelanocortin (POMC) deficiency causes a human syndrome of hypoadrenalism, altered skin and hair pigmentation, and severe hyperphagic obesity. Heterozygote carriers of nonsense mutations are strongly predisposed to obesity. Pomc(+/-) mice have normal body weight on a chow diet but increase food intake and become more obese than wild-type littermates when placed on a high-fat diet. To further explore the mechanisms whereby dietary fat interacts with Pomc genotype to produce obesity, we examined Pomc-null, Pomc(+/-), and wild-type mice for changes in the components of energy balance in response to provision of a high-fat diet and macronutrient preference when presented with a selection of dietary choices. In contrast to wild-type mice, Pomc null mice did not increase their resting energy expenditure or their spontaneous physical activity when given a high-fat diet. Pomc(+/-) mice increased resting energy expenditure similarly to wild types, but their increase in physical activity was significantly less than that seen in wild-type mice. In two independent experimental tests of macronutrient preference, Pomc genotype was a strong predictor of dietary fat preference with Pomc null animals choosing to eat approximately twice as much fat, but similar amounts of carbohydrate and protein, as wild-type animals. Pomc(+/-) mice showed an intermediate response. In summary, POMC-derived peptides have influences on multiple aspects of the organism's response to the presentation of high-fat diet. This includes a major influence, readily discernible even in heterozygote animals, on the dietary preference for fat.
authors: Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK.
authors: Y C Loraine
authors: YC
authors: Tung
authors: Debra
authors: D
authors: Rimmington
authors: Stephen
authors: S
authors: O'Rahilly
authors: Anthony P
authors: AP
authors: Coll
mesh_terms: D000818:Animals; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005518:Food Preferences / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000502:physiology*; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics*
chemical_list: D004041:Dietary Fats; D011333:Pro-Opiomelanocortin
references: Nat Neurosci. 2001 Jun;4(6):605-11
references: 11369941
references: Am J Physiol Regul Integr Comp Physiol. 2001 Mar;280(3):R814-21
references: 11171662
references: Neuroscience. 2002;111(2):379-87
references: 11983323
references: Endocrinology. 2002 Aug;143(8):2995-3000
references: 12130565
references: Regul Pept. 2003 May 15;113(1-3):85-8
references: 12686465
references: Endocrinology. 2003 May;144(5):1753-60
references: 12697680
references: J Clin Endocrinol Metab. 2003 Oct;88(10):4633-40
references: 14557433
references: Am J Physiol Regul Integr Comp Physiol. 2004 Feb;286(2):R311-9
references: 14592933
references: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4695-700
references: 15070780
references: Neurosci Lett. 2004 Oct 7;369(1):75-9
references: 15380311
references: Peptides. 1985 Nov-Dec;6(6):1205-11
references: 3841735
references: Neuroendocrinology. 1992 Jan;55(1):9-13
references: 1319008
references: Brain Res Mol Brain Res. 1992 Sep;15(1-2):27-32
references: 1331668
references: Mol Endocrinol. 1994 Oct;8(10):1298-308
references: 7854347
references: Mol Pharmacol. 1996 Sep;50(3):583-91
references: 8794897
references: Nat Genet. 1997 Mar;15(3):273-6
references: 9054940
references: Crit Rev Neurobiol. 1997;11(1):35-57
references: 9093813
references: Peptides. 1997;18(8):1279-87
references: 9396074
references: Nat Genet. 1998 Jun;19(2):155-7
references: 9620771
references: Neurosci Lett. 1998 Jun 19;249(2-3):107-10
references: 9682828
references: J Neurosci. 1999 Mar 15;19(6):2362-7
references: 10066286
references: Science. 1951 Jun 29;113(2948):745-6
references: 14854870
references: Am J Clin Nutr. 2004 Nov;80(5):1410-4
references: 15531694
references: Nat Med. 2005 Mar;11(3):320-7
references: 15735652
references: Int J Obes (Lond). 2005 Apr;29(4):420-8
references: 15597110
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R117-24
references: 15731402
references: Cell Metab. 2005 Jan;1(1):53-61
references: 16054044
references: J Clin Invest. 2006 Feb;116(2):495-505
references: 16440060
references: Diabetes. 2006 Sep;55(9):2549-53
references: 16936203
references: Neuroscience. 2007 Jan 5;144(1):17-25
references: 17049174
references: Bioessays. 2007 Mar;29(3):248-61
references: 17295284
references: Am J Physiol Regul Integr Comp Physiol. 2000 Apr;278(4):R797-805
references: 10749765
references: Physiol Behav. 1999 Nov;67(5):809-12
references: 10604855
references: Brain Res. 1999 Dec 18;851(1-2):198-203
references: 10642844
references: J Clin Invest. 2000 Apr;105(7):1005-11
references: 10749579
references: Science. 2000 Jun 30;288(5475):2379-81
references: 10875926
references: Am J Physiol Endocrinol Metab. 2000 Oct;279(4):E838-45
references: 11001766
references: Science. 2000 Sep 22;289(5487):2066-7
references: 11032558
references: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12339-44
references: 11027312
references: Diabetes. 2002 Feb;51(2):271-5
references: 11812732