title: Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats.
abstract: Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/- heparin (IL, IL(H), respectively) or saline/heparin (SH) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with IL(H)/S(H); and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with IL(H)/S(H). IL(H) significantly lowered food intake during refeeding compared to S(H) (p<0.001). Five hours after refeeding, etomoxir did not affect this inhibitory effect of IL(H) on food intake while VMN CD36 depletion totally prevented it. Triacsin C also prevented IL(H) effects on food intake. In conclusion, the effect of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but does not required FA oxidation.
authors.affiliation: Unit of Functional and Adaptive Biology, EAC 4413 CNRS, Université Paris Diderot, Paris, France.
authors.forename: Valentine S
authors.initials: VS
authors.lastname: Moullé
authors.forename: Christelle
authors.initials: C
authors.lastname: Le Foll
authors.forename: Erwann
authors.initials: E
authors.lastname: Philippe
authors.forename: Nadim
authors.initials: N
authors.lastname: Kassis
authors.forename: Claude
authors.initials: C
authors.lastname: Rouch
authors.forename: Nicolas
authors.initials: N
authors.lastname: Marsollier
authors.forename: Linh-Chi
authors.initials: LC
authors.lastname: Bui
authors.forename: Christophe
authors.initials: C
authors.lastname: Guissard
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
authors.forename: Anne
authors.initials: A
authors.lastname: Lorsignol
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.forename: Barry E
authors.initials: BE
authors.lastname: Levin
authors.forename: Céline
authors.initials: C
authors.lastname: Cruciani-Guglielmacci
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D004435:Eating; D004655:Emulsions / Q000008:administration & dosage; D050612:Fatty Acid Transport Proteins / Q000235:genetics; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology*; D015870:Gene Expression; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D010743:Phospholipids / Q000008:administration & dosage; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051381:Rats; D013024:Soybean Oil / Q000008:administration & dosage
chemical_list: D018955:CD36 Antigens; D004655:Emulsions; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D010743:Phospholipids; D016760:Proto-Oncogene Proteins c-fos; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil
references.citation: Physiol Behav. 2006 Aug 30;89(1):4-9
references.pmid: 16556452
references.citation: Nucleic Acids Res. 2002 May 1;30(9):e36
references.pmid: 11972351
references.citation: Circ Res. 1970 May;26(5):545-51
references.pmid: 5443132
references.citation: Am J Physiol. 1997 Jul;273(1 Pt 2):R442-5
references.pmid: 9249583
references.citation: J Nutr Sci Vitaminol (Tokyo). 2009;55(5):423-7
references.pmid: 19926929
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Sep;297(3):R655-64
references.pmid: 19535676
references.citation: Can J Physiol Pharmacol. 1992;70 Suppl:S118-29
references.pmid: 1295662
references.citation: Diabetes Metab. 2011 Apr;37(2):83-8
references.pmid: 21185213
references.citation: Physiol Behav. 2011 Nov 30;105(1):36-42
references.pmid: 21354192
references.citation: Diabetes. 2003 Feb;52(2):277-82
references.pmid: 12540597
references.citation: Endocrinology. 2011 Jul;152(7):2552-7
references.pmid: 21521751
references.citation: Diabetes. 2010 Sep;59(9):2117-25
references.pmid: 20573749
references.citation: J Clin Invest. 2005 Nov;115(11):3177-84
references.pmid: 16276419
references.citation: Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):458-62
references.pmid: 16778577
references.citation: Diabetes. 2002 Feb;51(2):271-5
references.pmid: 11812732
references.citation: Eur J Pharmacol. 2003 Nov 7;480(1-3):3-11
references.pmid: 14623345
references.citation: Nutrition. 1999 Nov-Dec;15(11-12):819-28
references.pmid: 10575655
references.citation: Physiol Behav. 1975 Apr;14(04):483-6
references.pmid: 1135293
references.citation: J Neurophysiol. 2006 Mar;95(3):1491-8
references.pmid: 16306178
references.citation: J Biol Chem. 1998 Oct 9;273(41):26383-7
references.pmid: 9756869
references.citation: Nat Neurosci. 2005 May;8(5):579-84
references.pmid: 15856066
references.citation: Am J Physiol. 1986 Jun;250(6 Pt 2):R1003-6
references.pmid: 3717372
references.citation: Cell Metab. 2011 Jan 5;13(1):105-13
references.pmid: 21195353
references.citation: Front Physiol. 2012 Sep 28;3:385
references.pmid: 23060810
references.citation: Mol Cell Biochem. 2010 Nov;344(1-2):99-107
references.pmid: 20607591
references.citation: Physiol Behav. 2008 Mar 18;93(4-5):930-6
references.pmid: 18234246
references.citation: Diabetes. 2007 Jan;56(1):152-60
references.pmid: 17192477
references.citation: Front Biosci (Schol Ed). 2009 Jun 01;1:448-65
references.pmid: 19482713
references.citation: Am J Physiol. 1990 Jun;258(6 Pt 2):R1395-401
references.pmid: 2360688
references.citation: Behav Brain Res. 2010 May 1;209(1):1-12
references.pmid: 20035790
references.citation: Cell Metab. 2012 May 2;15(5):646-55
references.pmid: 22560217
references.citation: J Biol Chem. 2008 May 9;283(19):12949-59
references.pmid: 18321850
references.citation: J Neurochem. 1999 Oct;73(4):1674-82
references.pmid: 10501215
references.citation: PLoS One. 2009 Aug 14;4(8):e6649
references.pmid: 19680547
references.citation: Front Neuroendocrinol. 2010 Jan;31(1):4-15
references.pmid: 19729032
references.citation: Annu Rev Nutr. 2012 Aug 21;32:147-60
references.pmid: 22540257
references.citation: J Clin Endocrinol Metab. 2009 May;94(5):1781-8
references.pmid: 19223522
references.citation: Nat Med. 2003 Jun;9(6):756-61
references.pmid: 12754501
references.citation: Diabetologia. 2004 Nov;47(11):2032-8
references.pmid: 15599702