EFFECT ON THE ENERGETIC METABOLISM AND TERMOGENESIS OF SIRT1 AND SIRT3 IN BAT IN HFD-INDUCED INSULIN RESISTANCE STATES AND ON AGING (Q3162163): Difference between revisions
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(Created claim: summary (P836): THE ROLE OF TERMOGENESIS IN ENERGETIC HOMEOSTASIS HAS AROUSED GREAT CLINICAL INTEREST IN THE IDENTIFICATION OF MARRON ADIPOSE TISSUE (BAT) IN ADULT HUMANS. IN ADDITION TO ITS ROLE IN THERMOREGULATION, BAT IS INVOLVED IN THE CONTROL OF GLUCOSE, LIPID METABOLISM AND IT IS KNOWN THAT STATES OF INSULIN RESISTANCE PRODUCE A DECREASE IN THE THEROGENIC PROGRAM. ON THE OTHER HAND, AGE IS ASSOCIATED WITH SEVERE FAILURE IN TERMOGENESIS AND DECREASE IN MAS...) |
(Changed label, description and/or aliases in en: translated_label) |
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EFFECT ON THE ENERGETIC METABOLISM AND TERMOGENESIS OF SIRT1 AND SIRT3 IN BAT IN HFD-INDUCED INSULIN RESISTANCE STATES AND ON AGING | |||
Revision as of 18:09, 12 October 2021
Project Q3162163 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | EFFECT ON THE ENERGETIC METABOLISM AND TERMOGENESIS OF SIRT1 AND SIRT3 IN BAT IN HFD-INDUCED INSULIN RESISTANCE STATES AND ON AGING |
Project Q3162163 in Spain |
Statements
106,480.0 Euro
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133,100.0 Euro
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80.0 percent
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30 December 2016
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29 December 2020
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UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
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42°52'49.51"N, 8°32'45.10"W
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15078
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EL PAPEL DE LA TERMOGENESIS EN LA HOMEOSTASIS ENERGETICA HA SUSCITADO GRAN INTERES CLINICO POR LA IDENTIFICACION DE TEJIDO ADIPOSO MARRON (BAT) EN HUMANOS ADULTOS. ADEMAS DE SU PAPEL EN LA TERMORREGULACION, BAT ESTA IMPLICADO EN EL CONTROL DE LA GLUCOSA, DEL METABOLISMO LIPIDICO Y SE SABE QUE ESTADOS DE RESISTENCIA A LA INSULINA PRODUCEN UNA DISMINUCION DEL PROGRAMA TERMOGENICO. POR OTRA PARTE, LA EDAD ESTA ASOCIADA A UN SEVERO FALLO EN LA TERMOGENESIS Y DESCENSO DE MASA Y ACTIVIDAD DE BAT. SIN EMBARGO LOS FACTORES QUE PUEDEN ESTAR INFLUYENDO EN LA DISFUNCION DEL BAT CON LA EDAD SON DESCONOCIDOS. LAS SIRTUINAS, PROTEINAS MUY ESTUDIADAS EN RELACION A RESTRICCION CALORICA Y ENVEJECIMIENTO HAN SIDO UNAS DE LAS CANDIDATAS. ENTRE ELLAS SIRT1, UNA DEACETILASA NAD-DEPENDIENTE INVOLUCRADA EN UNA AMPLIA VARIEDAD DE PROCESOS CELULARES. SE ACTIVA EN RESTRICCION CALORICA Y ACTUA EN DIFERENTES TEJIDOS (MUSCULO, ESTOMAGO, WAT, ETC) COMO MEDIADOR DE FUNCIONES ENDOCRINAS RELACIONADAS CON LA MODULACION DEL BALANCE ENERGETICO. SE HA LIGADO A SIRT1 CON UNA POSIBLE REGULACION DEL ¿BROWNING¿ EN BAT, PERO LOS MECANISMOS A TRAVES LOS CUALES SIRT1 INFLUIRIA EN LA DISREGULACION DE TERMOGENESIS POR LA EDAD EN BAT Y ALTERACIONES EN HOMEOSTASIS ENERGETICA NO ESTA DEFINIDA. SIRT3 OTRO MIEMBRO DE LA FAMILIA ESTA LOCALIZADA EN LA MITOCONDRIA (ORGANELA CLAVE EN METABOLISMO CELULAR Y TERMOGENESIS) REGULA LA OXIDACION DE AC GRASOS DURANTE EL AYUNO Y LA PRODUCCION DE ATP ENTRE OTROS EFECTOS. DATOS DE NUESTRO GRUPO (NO PUBLICADOS) MUESTRAN BAJOS NIVELES DE SIRT1 Y SIRT3 EN BAT DE ANIMALES VIEJOS, MENOR TEMPERATURA ESCAPULAR Y DISMINUCION DE UCP1 Y PGC1ALFA RESPECTO A ANIMALES JOVENES. ESTO INDICARIA QUE LA ALTERACION EN EL PROGRAMA TERMOGENICO POR LA EDAD PODRIA ESTAR INFLUENCIADA POR LA DISMINUCION DE SIRT1 O SIRT3 O DE AMBOS. POR TODO ELLO NUESTRO PRINCIPAL OBJETIVO SERA ESTUDIAR EL PAPEL Y MECANISMOS A TRAVES DE LOS CUALES SIRT1 (NUCLEAR) Y SIRT3 (MITOCONDRIAL) PODRIAN ACTUAR DIRECTAMENTE EN EL BAT Y EN SU REGULACION SOBRE EL PROGRAMA TERMOGENICO, METABOLISMO LIPIDICO Y DE LA GLUCOSA Y SI SU DISMINUCION ES RESPONSABLE DE LAS ALTERACIONES QUE SE PRODUCEN EN ESTADOS DE RESISTENCIA A LA INSULINA INDUCIDA POR DIETA Y POR EL ENVEJECIMIENTO. _x000D_ PARA TESTAR NUESTRA HIPOTESIS DESARROLLAREMOS ESTRATEGIAS DE PERDIDA O GANANCIA DE FUNCION TEJIDO-ESPECIFICO, BAT, TANTO PARA SIRT1 COMO PARA SIRT3 Y POSTERIOR ESTUDIO DE FENOTIPADO METABOLICO COMPLETO Y ANALISIS MOLECULAR. POR OTRA PARTE, Y COMO ESTRATEGIA COMPLEMENTARIA, PARA EVITAR EFECTOS DE COMPENSACIONES DURANTE ETAPAS CRITICAS DEL DESARROLLO UTILIZAREMOS TECNICAS DE VIROGENETICAS (AAV) SOBREXPRESANDO O DELECCIONANDO SIRT1/SIRT3 ESPECIFICAMENTE EN EL BAT EN RATON ADULTO CON RESISTENCIA A INSULINA Y ENVEJECIDOS. EN ESTE CASO UTILIZAREMOS RATON MACHO Y HEMBRA PARA PODER DESCARTAR O NO LA INFLUENCIA DEL GENERO SOBRE LA ACTIVIDAD TERMOGENICA. ESTOS EXPERIMENTO SERAN DE GRAN IMPORTANCIA Y REALIZARAN EN PRIMER LUGAR DANDONOS INFORMACION PRECISA PARA UNA MEJOR ESTRATEGIA DE ABORDAJE DEL ESTUDIO DE LOS MODELOS DE RATON A GENERAR POSTERIORMENTE._x000D_ LOS RESULTADOS OBTENIDOS PODRIAN SEÑALAR A SIRT1, A SIRT3 O A AMBAS COMO ELEMENTOS CON UN IMPORTANTE PAPEL EN LA REGULACION DEL METABOLISMO DEL BAT. SIENDO EN ESTE CASO LOS ACTIVADORES DE SIRT1/SIRT3 POTENCIALMENTE UTILES PARA LA REGULACION DE LA TERMOGENESIS Y POR TANTO HOMEOSTASIS ENERGETICA Y MEJORA DE LAS ALTERACIONES METABOLICAS ASOCIADAS ALA EDAD Y LA RESISTENCIA A INSULINA. (Spanish)
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THE ROLE OF TERMOGENESIS IN ENERGETIC HOMEOSTASIS HAS AROUSED GREAT CLINICAL INTEREST IN THE IDENTIFICATION OF MARRON ADIPOSE TISSUE (BAT) IN ADULT HUMANS. IN ADDITION TO ITS ROLE IN THERMOREGULATION, BAT IS INVOLVED IN THE CONTROL OF GLUCOSE, LIPID METABOLISM AND IT IS KNOWN THAT STATES OF INSULIN RESISTANCE PRODUCE A DECREASE IN THE THEROGENIC PROGRAM. ON THE OTHER HAND, AGE IS ASSOCIATED WITH SEVERE FAILURE IN TERMOGENESIS AND DECREASE IN MASS AND BAT ACTIVITY. HOWEVER, THE FACTORS THAT MAY BE INFLUENCING BAT DYSFUNCTION WITH AGE ARE UNKNOWN. SIRTUINS, PROTEINS VERY STUDIED IN RELATION TO CALORIC RESTRICTION AND AGING HAVE BEEN AMONG THE CANDIDATES. AMONG THEM SIRT1, A NAD-DEPENDENT DEACETYLASE INVOLVED IN A WIDE VARIETY OF CELLULAR PROCESSES. IT IS ACTIVATED IN CALORIC RESTRICTION AND ACTS IN DIFFERENT TISSUES (MUSCLE, STOMACH, WAT, ETC.) AS A MEDIATOR OF ENDOCRINE FUNCTIONS RELATED TO ENERGY BALANCE MODULATION. IT HAS BEEN LINKED TO SIRT1 WITH A POSSIBLE REGULATION OF BAT BROWNING, BUT THE MECHANISMS THROUGH WHICH SIRT1 WOULD INFLUENCE THE DISREGUATION OF TERMOGENESIS BY AGE IN BAT AND ALTERATIONS IN ENERGETIC HOMEOSTASIS IS NOT DEFINED. SIRT3 ANOTHER MEMBER OF THE FAMILY IS LOCATED IN THE MITOCHONDRIA (KEY ORGAN IN CELL METABOLISM AND TERMOGENESIS) REGULATES THE OXIDATION OF FATTY AC DURING FASTING AND THE PRODUCTION OF ATP AMONG OTHER EFFECTS. DATA FROM OUR GROUP (UNPUBLISHED) SHOW LOW LEVELS OF SIRT1 AND SIRT3 IN BAT OF OLD ANIMALS, LOWER ESCAPULAR TEMPERATURE AND DECREASE OF UCP1 AND PGC1ALFA COMPARED TO YOUNG ANIMALS. THIS WOULD INDICATE THAT THE ALTERATION IN THE THEROGENIC PROGRAM BY AGE COULD BE INFLUENCED BY THE DECREASE OF SIRT1 OR SIRT3 OR BOTH. THEREFORE OUR MAIN OBJECTIVE WILL BE TO STUDY THE ROLE AND MECHANISMS THROUGH WHICH SIRT1 (NUCLEAR) AND SIRT3 (MITOCHONDRIAL) COULD ACT DIRECTLY IN THE BAT AND IN ITS REGULATION ON THE THERMAL PROGRAM, LIPID METABOLISM AND GLUCOSE AND IF ITS DECREASE IS RESPONSIBLE FOR THE ALTERATIONS THAT OCCUR IN STATES OF INSULIN RESISTANCE INDUCED BY DIET AND AGING. _x000D_ to TEST OUR HYPOTESIS we will develop loss STRATEGYS OR GINENCE OF TECHNOLOGY-SPECT, BAT, TANTO FOR SIRT1 AS FOR SIRT3 AND POSTERIOR STUDY of COMPLETE METABOLIC phenotyping and MOLECULAR ANALISIS. ON THE OTHER HAND, AND AS A COMPLEMENTARY STRATEGY, TO AVOID THE EFFECTS OF COMPENSATION DURING CRITICAL STAGES OF DEVELOPMENT WE WILL USE TECHNIQUES OF VIROGENETICAS (AAV) SOBREXPRESANDO OR DELECTIONANDO SIRT1/SIRT3 SPECIFICALLY IN THE BAT IN ADULT RATON WITH INSULIN RESISTANCE AND AGED. IN THIS CASE WE WILL USE MALE AND FEMALE RATON TO RULE OUT OR NOT THE INFLUENCE OF THE GENDER ON THE THERMAL ACTIVITY. These experiences will be of great importance and will be carried out in the first place by giving us accurate information for a better sTRATEGY OF THE STUDY OF THE RATON MODEL TO GENERATE POSTERORORENT._x000D_ OBTENTED RESULTS can be seen to SIRT1, SIRT3 or AMBAS AS ELEMENTS WITH A IMPORTANT PAPEL IN THE REGULATION OF BAT METABOLISM. IN THIS CASE SIRT1/SIRT3 ACTIVATORS ARE POTENTIALLY USEFUL FOR THE REGULATION OF TERMOGENESIS AND THEREFORE HOMEOSTASIS ENERGETICA AND IMPROVEMENT OF METABOLIC ALTERATIONS ASSOCIATED WITH AGE AND INSULIN RESISTANCE. (English)
12 October 2021
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Santiago de Compostela
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Identifiers
BFU2016-79208-R
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