¿Cómo elegimos lo que comemos? El sistema dopaminérgico como un sensor calórico

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Conferencia de Luis Teellez en el Congreso Internacional de Nutrición y Salud Dr. José María Bengoa. Realizado en Caracas el 26 y 27 de Octubre de 2013.

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¿Cómo elegimos lo que comemos? El sistema dopaminérgico como un sensor calórico

  1. 1. !"#$%&'"()#*&%#+,-"#+.(/&(01*%-,-2#(3(4+.1/( 879&:%+6&;27<2&='5)%2( !"#$%&'(')*$%+&(%&,-'&.%$'$%+/& 0(&+*+1'$2&3%42$*567)*.%& .%$%&-5&+'5+%7&.2(#7*.%&& Luis Téllez & Universidad de Yale 5"6-#$"7(89(/&(",*1:%&7(8;<=(
  2. 2. Congreso  Internacional  de  Nutrición  Dr.  José  María  Bengoa     Caracas,  Venezuela    ¿Cómo  elegimos  lo  que  comemos?     El  sistema  dopaminérgico  como  un   sensor  calórico.  
  3. 3. :";&"'*<=,"& D')-(2&'(&.%5+-$%&3'&2(*$'51%&'5&E-5.*#5& 3'(&)2+1%&'5'7)6F.%& :&/2#-,"(( A5%&B";&"'*<=,"C&& >+(,";-/+(,";"(?1&#*&(/&(@.+,&%& (E"'(+.-6&#*"'(A'+B%"'"'A(+,*F+#('":%&(."'( '-'*&6+'(/&(%&,"6B&#'+(/&.(,&%&:%"7(3(B1&/&#( '1B%-6-%(+(."'(6&,+#-'6"'(/&(%&$1.+,-2#( G"6&"'*HI,+D(
  4. 4. Tellez L A et al. J Physiol 2013
  5. 5. !"#$%&7')-(2&'(&+*+1'$2& 5'7G*%+%&.'5172(&(2&*5)'+12& 3'&2(*$'51%+/&
  6. 6. El Sistema Dopaminérgico Nigrostriatal… • Juega un papel crítico en la conducta (e.g. atención, motivación, recompensa, la conducta dirigida por objetivos, y la adquisición de “hábitos” , incluyendo la auto-administración de drogas); • Los ratones deficientes en DA mueren de hambre, un efecto que puede ser revertido mediante la restauración farmacológica de DA en el estriado dorsal; • Los niveles extracelulares de DA se incrementan durante la ingestión de alimentos.
  7. 7. <K;( J.1,"'&( 41,%+."'&( N&"B25)'&8O& <M;( <8;( <;;( L;( K;( <( 8( =( M( N( K( H*$'&IJKL$*5M& Tellez L A et al. J Physiol 2013
  8. 8. ¿Es  posible  regular  la  ingesta  calórica   en  ausencia  de  esFmulación   gustaFva?  
  9. 9. 1000   3.5   900   800   3   600   500   400   2.5   kcal   Licks   700   2   300   200   1.5   100   0   1    Tellez  LA  et  al.  Biological  Psychiatry  2013  
  10. 10. Los  niveles  extracelulares  de  dopamina  en  el   estriado  reflejan  la  ingesta  calórica,  incluso   en  la  ausencia  de  señales  gusta=vas.  
  11. 11. En  ausencia  de  señales  gustaFvas,  bloquear  el  receptor  de   dopamina  interrumpe  la  detección  de  calorías. ©2012 by The Physiological Society Ferreira J G et al. J Physiol 2012
  12. 12. ¿Cómo  afecta  el  estado   metabólico  a  este  sensor   calórico?  
  13. 13.  La  respuesta  dopaminérgica  se  encuentra   alterada  en  organismos  obesos.   (Wang  et  al,  2001)   Se  ha  propuesto  que  la  disminución  en  la  función   dopaminérgica  conlleva  a  la  sobrealimentación  como  un   mecanismo  compensatorio.   (Johnson  &  Kenny,  2010)  
  14. 14. Q2&'J4%+*.*#5&.7#5*.2&2&-52&3*'12&2(12&'5&)72+2&&)'5'72&-52& 7'+4-'+12&/"@+;-#6%$-,+&3'].*'51'&172+&(2&*5E-+*#5&3'& (<4*3%+&'5&'(&172.1%&3*)'+FG%( <DK( "B25)'&*5&8O& <DM( <D8( <( ;DL( ;DK( <( 8( =( M( N( K( 9( L( O( ^2$4('&IJ&_&$*5M& :-$E(F+*(G;1.'-"#( <;( <<( <8( <=( <M(
  15. 15. ((!"-`(&'+&(2&7'(2.*#5&]+*%(#)*.2&'517'&-5& .%5+-$%&2(1%&'5&)72+2+&3-7251'&4'7*%3%+& 47%(%5)23%+&T&(2&3'].*'5.*2&'5&(%+& 5*G'('+&3'&3%42$*52/&
  16. 16. G'(1#(E&,E"(B-&#(,"#",-/"(H1&(.+( +.*&%+,-2#(/&(.+(?1#,-2#( $+'*%"-#*&'=#+.(&'(1#"(/&(."'( &?&,*"'(/&(1#+(/-&*+(+.*+(&#( aH^& $%+'+'(I( 3%7+2(& +-P3*24B72)$2F.& G2)-+& G'5172(& +-P3*24B72)$2F.& G2)-+& a'%.%71'J& ^17*21-$& S=a& ^ab?HO& Sc"& ;'3*2(&& E%7'P72*5&P-53('&
  17. 17. Q%+&'E'.1%+&4%+1d*5)'+F%52('+&*5W-'5.*25& '(&.%5+-$%&3'&2(*$'51%+9&e52&3'1'..*#5& 25%7$2(&3'&(%+&5-17*'51'+&47'+-4%5'&(2& 2.FG2.*#5>&12$P*65&25%7$2(>&3'&(%+& aH^& .*7.-*1%+&3'&7'.%$4'5+2f& a'%.%71'J& ^17*21-$& S=a& ^ab?HO& Sc"& ;'3*2(&& E%7'P72*5&P-53('& 3%7+2(& +-P3*24B72)$2F.& G2)-+& G'5172(& +-P3*24B72)$2F.& G2)-+& '9)9&(2&7'3-..*#5&'5&(%+&5*G'('+& )2+17%*51'+F52('+&3'&adO.T('125%(2$*52+& IaO0+M>&-52&E2$*(*2&3'&$'5+2X'7%+&(*4<3*.%+&,-'& 7')-(25&'(&.%5+-$%&3'&2(*$'51%+9&
  18. 18. g0O&I%('*(d'125%(2$*52M& 7&#'+L&%"(.-@8/-,"M(/&%-D+/"(/&.(<,-/"(".&-,"(@%"D&#-&#*&(/&(.+(-#$&'*+(H1&(&'( @%"/1,-/"(&#(&.(-#*&'=#"(/&.$+/"I(( J#(,";@"#&#*&(,.+D&(/&(.+(;+H1-#+%-+(;".&,1.+%(%&'@"#'+B.&(/&(;"#-*"%&+%(.+( -#$&'*+(/&($%+'+'I( F1#,-"#+(,";"(1#(?+,*"%(/&('+,-&/+/I(& '1('8#*&'-'(&'('1@%-;-/+(*%+'(.+(&K@"'-,-2#(@%"."#$+/+(+(/-&*+(+.*+I(
  19. 19. Daniele    Piomelli   Trends  in  Endocrinology  &amp;  Metabolism   Volume  24,  Issue  7  2013  332  -­‐  341  
  20. 20. 05&721%5'+&.%5&-52&3*'12&P2X2&'5&)72+2>&(2&g0O&.2-+#&'E'.1%+&+*)5*].2FG%+&'5& (2&(*P'72.*#5&3'&8O&172+&(2&23$*5*+172.*#5&*5172d)`+17*.2+&3'&'$-(+*%5'+&P2X2+& '5&.2(%7<2+( <DN( <DM( <D=( <D8( E-$E( <D<( <( ;DO( ;DL( ;D9( ;DK( <( 8( =( M( N( K( 9( L( O( <;( <<( <8( <=( <( 8( =( M( N( K( 9( L( O( <;( <<( <8( <=( <D=( <D8( <D<( ."N( <( ;DO( ;DL( ;D9( ;DK(
  21. 21. E-$E( "B25)'&*5&8O& G#(%+*"#&'(,"#(1#+(/-&*+(+.*+(&#($%+'+'M(.+(+/;-#-'*%+,-2#(/&(OGP(@%"/1,&(.+( %&,1@&%+,-2#(/&(.+(%&'@1&'*+(/"@+;-#6%$-,+(-#/1,-/+(@"%(.+(-#?1'-2#(*5172d )`+17*.2(/&(.8@-/"'4(( <D=( <D8( <D<( <( ;DO( ;DL( ;D9( ;DK( <( 8( =( M( N( K( 9( L( O( <;( <<( <8( <=( <( 8( =( M( N( K( 9( L( O( <;( <<( <8( <=( ."N( N&"B25)'&*5&8O& <D=( <D8( <D<( <( ;DO( ;DL( ;D9( ;DK( ^2$4('&IJ&_&$*5M& YAZ[(<;6$]$(
  22. 22. (0J*+1'&-52&G<2&E-5.*%52(&,-'& *51'7.%5'.12&(2&3'1'..*#5&3'&(<4*3%+& '5&'(&172.1%&3*)'+FG%&T&(2&(*P'72.*#5& 3'&8O&'5&'(&$'+'5.6E2(%999& aH^& a'%.%71'J& ^17*21-$& S=a& ^ab?HO& Sc"& ;'3*2(&& E%7'P72*5&P-53('& 3%7+2(& +-P3*24B72)$2F.& G2)-+& G'5172(& +-P3*24B72)$2F.& G2)-+& f&(2&.-2(&+'&2E'.12&.%5&-52&3*'12& 2(12&'5&)72+2+&
  23. 23. ¿Cuáles  son  las  consecuencias   conductuales  derivadas  del   incremento  en  los  niveles  de  DA   inducidos  por  la  OEA?  
  24. 24. E^( E-$E( ."N( _^(
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
  27. 27. 0(&+*+1'$2&3%42$*567)*.%&E-5.*%52&.%$%&-5&+'5+%7&.2(#7*.%& ,-'&*51')72&+'Y2('+&B%$'%+1`F.2+&T&AE&/2#-,+'Rm(( •! >+(/&Q,-&#,-+(/"@+;-#6%$-,+(/&%-D+/+(/&(.+("B&'-/+/(@1&/&('&%(%&'1.*+/"( /&(,+;B-"'(&#(&.(*%+,*"($+'*%"-#*&'=#+.(-#/1,-/"'(@"%(.+(@%"#"#$+/+( -#$&'*+(/&($%+'+S!! •! G#(&'@&,-Q,"M(&'*+(/&Q,-&#,-+(@"/%8+(@%"D&#-%(/&(1#+(,";1#-,+,-2#( /&Q,-&#*&(&#*%&(&.(*%+,*"($+'*%"-#*&'=#+.(T(&.(,&%&B%"M(;&/-+/+(@"%(&.( #&%D-"(D+$"S( •! >"'(;&#'+L&%"'(.-@8/-,"'(U,";"(.+(OGPU(@"/%8+#(&'*+%(?1#,-"#+#/"(,";"( '&C+.&'(/&(+1*"%%&$1.+,-2#(H1&(/-,*+#(.+'(,+#=/+/&'(/&($%+'+'(H1&(/&B&#( '&%(-#$&%-/+'S( •! G#(-#/-D-/1"'("B&'"'M(&.(%&'*+B.&,-;-&#*"(/&(.+('&C+.-V+,-2#(@&%;-*&( %&,"B%+%(*+#*"(.+(&'=;1.+,-2#(/"@+;-#6%$-,+(,";"(/&(-#$&'*+(/&( +.-;&#*"'(,"#(B+L"(,"#*&#-/"(.-@8/-,"4!! 8'5%G25&S9&&='))&>&^1'4B'5&"9&&Z%%3+& "'((&;'12P%(*+$&?%(-$'&Kh>&i++-'&j&ULKV&jkl&d&j_L&
  28. 28. Gracias Fundación Bengoa para la Yale University Alimentación y Nutrición Ivan E. de Araujo Sara Medina Jozelia Ferreira Wenfei Han Xueying Ren Dana Small Tukiet Lam Funding National Institute on Deafness and Other Communication Disorders (NIDCD) National Institute on Diabetes, Digestion and Kidney (NIDDK) Ajinomoto, Inc. Albert Einstein College of Medicine Gary J Schwartz
  29. 29. (J1*7(I think this is the beginning of a beautiful friendship!
  30. 30. P/;-#-'*%+="#("?(OGP(%&,"D&%'(W1*UX=;1.+*&/(F&&/-#$(-#( :-$EUF+*(F&/(7-,&(( Qc& oc& 8DN( .2(& =( 8DN( .2(& =DN( =( VLN& =DN( 8( <DN( <( <DN( <( ;DN( ;( 8( <( 8( =( M( M( N( N( K( K( 9( 9( L( L( ;( O( <;( O( <;( 8( =( =( M( M( N( N( K( K( 9( L( O( <;( 9( L( O( <;( M( M( N( N( K( K( 9( L( O( <;( 9( L( O( <;( 8DN( .2(& =( 8DN( <( =DN( =( .2(& =DN( n9kN& _^XWA_( _^XYAZ( ;DN( E^XWA_( E^XYAZ( 8( <DN( <( <DN( <( E^XWA_( ;DN( ;( 8( E^XYAZ( <( 8( =( _^XWA_( ;DN( M( M( N( N( K( K( 9( 9( L( L( O( <;( O( <;( ;( _^XYAZ( <( 8( =( =(
  31. 31. !"#$%$&'()&!)*!+','#!'-./.&01!%$%$23.4!1)%.!)*!05.!6.5'+$)/'#!25)$2.! 4.72$01!)61./+.4!$&!5$,58*'0!*.4!%$2.( E^( _^( M( M( =DN( =DN( =( .2(& ;`( .2(& =( 8DN( 8( 8( <DN( <DN( <( <( ,E^XWA_( <( 8( =( M( N( K( 9( L( ;DN( ,E^XYAZ( ;DN( ;( 8DN( ;( O( M( N( K( 9( L( O( <;( 8DN( .2(& =( 8DN( =( =DN( =( 8( M( =DN( .2(& M( 9DN`( <( <;( 8( <DN( <DN( <( ,E^XWA_( ;DN( ;( 8( ,E^XYAZ( <( 8( =( M( N( K( 9( L( O( <;( <( ;DN( ;( <( 8( =( M( N( K( 9( L( O( <;(
  32. 32. n.s.   8   30   25   pmol/g   6   4   2   20   15   10   5   0   0   Serum   n.s.   140   120   100   pmol/g   pmol/mL   n.s.   80   60   40   20   0   Brain   Liver  
  33. 33. Dopaminergic  effects  of  OEA  are  mediated  by  the  nuclear   receptor  PPAR-­‐α  and  by  the  vagus   PPAR-­‐α  KO   capsaicin  treatment  
  34. 34. <;;( MD;;( =D;;( q& <D;;( ;D;;( X<D;;( 9;( K;( N;( M;( =;( 8;( X8D;;( <;( X=D;;( XMD;;( L;( .2(bp''R& "&=Z&I)M& 8D;;( q& O;( ;( <(((((((((((8((((((((((=(((((((((((M(((((((((((N(((((((((((((K(((((((((9(((((((((((L((((((((((O( ( ( <( 8( =( M( N( K( 9( L( O(

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