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ALTERACIONES EN LA HOMEOSTASIS DEL COLESTEROL HEPÁTICO Y SUS IMPLICACIONES EN LA ESTEATOHEPATITIS NO ALCOHÓLICA
ARTÍCULO DE REVISIÓN © 2017 Universidad Nacional Autónoma de México, Facultad de Estudios Superiores Zaragoza. Este es un artículo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). TIP Revista Especializada en Ciencias Químico-Biológicas, 20(1): 50-65, 2017. DOI: 10.1016/j.recqb.2016.11.005
ALTERACIONES EN LA HOMEOSTASIS DEL COLESTEROL HEPÁTICO Y SUS IMPLICACIONES EN LA ESTEATOHEPATITIS NO ALCOHÓLICA Joel Vega-Badillo1,2 Programa de Doctorado en Ciencias Bioquímicas, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Deleg. Coyoacán, C.P. 04510, Ciudad de México, México. 2Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Periférico Sur No. 4809, Colonia Arenal Tepepan, Deleg. Tlalpan, C.P. 14610, Ciudad de México, México. E-mail: [email protected]
1
RESUMEN
Diversos estudios han demostrado que el colesterol libre (CL) hepático tiene una participación importante en la patogénesis de la esteatohepatitis no alcohólica (EHNA). Estos estudios han proporcionado evidencias de que la acumulación en el hígado de CL es tóxico a distintos niveles incluyendo: daño oxidativo a la mitocondria, estrés del retículo endoplasmático (RE) y activación de células de Kupffer (CKs) y células estelares hepáticas (CEH). En conjunto, estas evidencias sugieren que el contenido de CL hepático es importante en HOLQLFLRPDQWHQLPLHQWR\PRGXODFLyQGHODUHVSXHVWDLQÁDPDWRULDDVRFLDGDDOD(+1$(QHVWDUHYLVLyQVH discuten los distintos mecanismos participantes en la regulación de la homeostasis del colesterol y sus posibles implicaciones en el desarrollo y progresión del hígado graso no alcohólico (HGNA).
Palabras Clave: FROHVWHUROOLEUH(+1$¿EURVLV+*1$KRPHRVWDVLV. Dysregulation in hepatic cholesterol homeostasis and its implications in nonalcoholic steatohepatitis
ABSTRACT
Several studies have shown that hepatic free cholesterol (FC) has an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). These studies have provided evidence that hepatic FC accumulation is toxic at different levels including: mitochondrial oxidative injury, endoplasmic reticulum (ER) stress, and activation of Kupffer cells (KCs) and hepatic stellate cell (HSCs). Altogether, this suggests that hepatic FC FRQWHQWLVLPSRUWDQWIRUWKHLQLWLDWLRQPDLQWHQDQFHDQGPRGXODWLRQRIWKHLQÁDPPDWRU\UHVSRQVHDVVRFLDWHG with NASH. In this review several mechanisms that participate in the regulation of cholesterol homeostasis and their possible implications in the development and progression of nonalcoholic fatty liver disease (NAFLD) are discussed.
Key Words: IUHHFKROHVWHURO1$6+¿EURVLV1$)/'KRPHRVWDVLV.
Nota: Artículo recibido el 18 de mayo de 2016 y aceptado el 28 de septiembre de 2016.
enero, 2017
Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
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TIP Rev.Esp.Cienc.Quím.Biol.
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enero, 2017
Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
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enero, 2017
Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
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Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
57
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COLESTEROL EN LA TOXICIDAD CELULAR Y PATOGÉNESIS DEL HGNA
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Figura 2. El aumento de colesterol en la membrana altera su estructura. (A) El colesterol se encuentra anclado HVWUDWpJLFDPHQWH HQ ODV PHPEUDQDV GH OD FpOXOD GRQGH PRGXODODÁXLGH]\SHUPHDELOLGDG/DPROpFXODGHFROHVWHURO constituye el elemento estructural básico del esqueleto de las PHPEUDQDVFHOXODUHVVLQVXUHIXHU]RODVPHPEUDQDVVHUtDQ H[WUHPDGDPHQWHÁXLGDV\SHUGHUtDQVXFRQVLVWHQFLD % (O aumento de los niveles de colesterol en la membrana afecta ODRUJDQL]DFLyQ\VXVSURSLHGDGHVItVLFDVORTXHGLVPLQX\HOD ÁXLGH]\DXPHQWDODULJLGH](QFRQVHFXHQFLDHVWRVHYHQWRV afectan negativamente a ciertas proteínas transmembranales, ODVFXDOHVUHTXLHUHQOLEHUWDGFRQIRUPDFLRQDOSDUDUHDOL]DUVXV funciones de manera apropiada. Basado en 21,112.
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REFERENCIAS 1. +DPDJXFKL0.RMLPD77DNHGD11DNDJDZD77DQLJXFKL +)XMLL.2PDWVX71DNDMLPD76DUXL+6KLPD]DNL 0 .DWR 7 2NXGD - ,GD . 7KH PHWDEROLF V\QGURPH DV D SUHGLFWRU RI QRQDOFRKROLF IDWW\ OLYHU GLVHDVH Ann. Intern. Med.143(10) )DQ-*=KX-/L;-&KHQ//L/'DL)/L) &KHQ 6<3UHYDOHQFHRIDQGULVNIDFWRUVIRUIDWW\OLYHULQDJHQHUDO SRSXODWLRQRI6KDQJKDL&KLQDJ. Hepatol. 43(3) '2, MMKHS 7LQLDNRV '* 9RV 0% %UXQW (0 1RQDOFRKROLF IDWW\ OLYHUGLVHDVH SDWKRORJ\DQGSDWKRJHQHVLVAnnu. Rev. Pathol. 5: '2, DQQXUHYSDWKRO .OHLQHU'(%UXQW(09DQ1DWWD0%HKOLQJ&&RQWRV 0- &XPPLQJV 2: )HUUHOO /' /LX <& 7RUEHQVRQ 068QDOS$ULGD$
enero, 2017
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Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
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ALTERACIONES EN LA HOMEOSTASIS DEL COLESTEROL HEPÁTICO Y SUS IMPLICACIONES EN LA ESTEATOHEPATITIS NO ALCOHÓLICA Joel Vega-Badillo1,2 Programa de Doctorado en Ciencias Bioquímicas, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Deleg. Coyoacán, C.P. 04510, Ciudad de México, México. 2Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Periférico Sur No. 4809, Colonia Arenal Tepepan, Deleg. Tlalpan, C.P. 14610, Ciudad de México, México. E-mail: [email protected]
1
RESUMEN
Diversos estudios han demostrado que el colesterol libre (CL) hepático tiene una participación importante en la patogénesis de la esteatohepatitis no alcohólica (EHNA). Estos estudios han proporcionado evidencias de que la acumulación en el hígado de CL es tóxico a distintos niveles incluyendo: daño oxidativo a la mitocondria, estrés del retículo endoplasmático (RE) y activación de células de Kupffer (CKs) y células estelares hepáticas (CEH). En conjunto, estas evidencias sugieren que el contenido de CL hepático es importante en HOLQLFLRPDQWHQLPLHQWR\PRGXODFLyQGHODUHVSXHVWDLQÁDPDWRULDDVRFLDGDDOD(+1$(QHVWDUHYLVLyQVH discuten los distintos mecanismos participantes en la regulación de la homeostasis del colesterol y sus posibles implicaciones en el desarrollo y progresión del hígado graso no alcohólico (HGNA).
Palabras Clave: FROHVWHUROOLEUH(+1$¿EURVLV+*1$KRPHRVWDVLV. Dysregulation in hepatic cholesterol homeostasis and its implications in nonalcoholic steatohepatitis
ABSTRACT
Several studies have shown that hepatic free cholesterol (FC) has an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). These studies have provided evidence that hepatic FC accumulation is toxic at different levels including: mitochondrial oxidative injury, endoplasmic reticulum (ER) stress, and activation of Kupffer cells (KCs) and hepatic stellate cell (HSCs). Altogether, this suggests that hepatic FC FRQWHQWLVLPSRUWDQWIRUWKHLQLWLDWLRQPDLQWHQDQFHDQGPRGXODWLRQRIWKHLQÁDPPDWRU\UHVSRQVHDVVRFLDWHG with NASH. In this review several mechanisms that participate in the regulation of cholesterol homeostasis and their possible implications in the development and progression of nonalcoholic fatty liver disease (NAFLD) are discussed.
Key Words: IUHHFKROHVWHURO1$6+¿EURVLV1$)/'KRPHRVWDVLV.
Nota: Artículo recibido el 18 de mayo de 2016 y aceptado el 28 de septiembre de 2016.
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Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
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TIP Rev.Esp.Cienc.Quím.Biol.
Vol. 20, No. 1
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enero, 2017
Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
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TIP Rev.Esp.Cienc.Quím.Biol.
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Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
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enero, 2017
Vega-Badillo, J.: El colesterol y la esteatohepatitis no alcohólica
57
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COLESTEROL EN LA TOXICIDAD CELULAR Y PATOGÉNESIS DEL HGNA
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Figura 2. El aumento de colesterol en la membrana altera su estructura. (A) El colesterol se encuentra anclado HVWUDWpJLFDPHQWH HQ ODV PHPEUDQDV GH OD FpOXOD GRQGH PRGXODODÁXLGH]\SHUPHDELOLGDG/DPROpFXODGHFROHVWHURO constituye el elemento estructural básico del esqueleto de las PHPEUDQDVFHOXODUHVVLQVXUHIXHU]RODVPHPEUDQDVVHUtDQ H[WUHPDGDPHQWHÁXLGDV\SHUGHUtDQVXFRQVLVWHQFLD % (O aumento de los niveles de colesterol en la membrana afecta ODRUJDQL]DFLyQ\VXVSURSLHGDGHVItVLFDVORTXHGLVPLQX\HOD ÁXLGH]\DXPHQWDODULJLGH](QFRQVHFXHQFLDHVWRVHYHQWRV afectan negativamente a ciertas proteínas transmembranales, ODVFXDOHVUHTXLHUHQOLEHUWDGFRQIRUPDFLRQDOSDUDUHDOL]DUVXV funciones de manera apropiada. Basado en 21,112.
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REFERENCIAS 1. +DPDJXFKL0.RMLPD77DNHGD11DNDJDZD77DQLJXFKL +)XMLL.2PDWVX71DNDMLPD76DUXL+6KLPD]DNL 0 .DWR 7 2NXGD - ,GD . 7KH PHWDEROLF V\QGURPH DV D SUHGLFWRU RI QRQDOFRKROLF IDWW\ OLYHU GLVHDVH Ann. Intern. Med.143(10) )DQ-*=KX-/L;-&KHQ//L/'DL)/L) &KHQ 6<3UHYDOHQFHRIDQGULVNIDFWRUVIRUIDWW\OLYHULQDJHQHUDO SRSXODWLRQRI6KDQJKDL&KLQDJ. Hepatol. 43(3) '2, MMKHS 7LQLDNRV '* 9RV 0% %UXQW (0 1RQDOFRKROLF IDWW\ OLYHUGLVHDVH SDWKRORJ\DQGSDWKRJHQHVLVAnnu. Rev. Pathol. 5: '2, DQQXUHYSDWKRO .OHLQHU'(%UXQW(09DQ1DWWD0%HKOLQJ&&RQWRV 0- &XPPLQJV 2: )HUUHOO /' /LX <& 7RUEHQVRQ 068QDOS$ULGD$
enero, 2017
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