Particularitățile metabolismului acizilor grași în miocard

Abstract

Cordul este considerat un organ cu un consum energetic foarte înalt. Cardiomiocitele permanent generează ATP, utilizat ulterior în contracție, procesele metabolice bazale și menținerea homeostaziei ionice. Actualmente se consideră că din totalul de ATP generat în miocard 50-70% se obțin din oxidarea acizilor grași (AG). Scopul acestui studiu este elucidarea particularităților metabolismului acizilor grași în miocard în condiții fiziologice. Calea metabolică de oxidare a acizilor grași reprezintă un proces complex dependent de un șir de factori regulatori. Controlul transcripțional al enzimelor implicate în metabolismul acizilor grași și biogeneza mitocondrială este unul din factorii determinanți ai ratei β-oxidării acizilor grași. Reglarea transcripțională a enzimelor este realizată de către factorii de transcripție a receptorilor nucleari, inclusiv PPAR și PGC-1. În miocard β-oxidarea acizilor grași reprezintă un proces dinamic, care se adaptează rapid la modificările (fiziologice și/sau patologice) consumului energetic sau mediului dat. Cercetările anterioare au prezentat date multiple și contradictorii privind rolul β-oxidării acizilor grași în acumularea intramiocardică a lipidelor. Datele recente confirmă ipoteza că ratele înalte de oxidare a acizilor grași (de ex. în obezitate sau diabet zaharat) sunt un factor important care contribuie la dezvoltarea cardiomiopatiilor..

The heart is considered an organ with high-energy demands. Cardiomyocytes permanently generate ATP to maintain contractile function, basal metabolic processes and ionic homeostasis. It is considered that in the myocardium 50-70% of the total ATP is obtained from the fatty acid oxidation. The aim of this study is to elucidate peculiarities of myocardial fatty acid metabolism in physiological conditions. Fatty acid β-oxidation is a complex process dependent upon a number of regulatory factors. The transcriptional control of the enzymes involved in fatty acid metabolism and mitochondrial biogenesis is one of the determinants of the rate of fatty acid β-oxidation. Transcriptional control of the enzymes is regulated by nuclear receptor transcription factors that include PPARs and PGC-1. Cardiac fatty acid β-oxidation is a dynamic process that adapts quickly to the (physiological and/or pathological) changes in cardiac energy demands and changing environment. Previous researches have shown multiple controversial data regarding the fatty acid β-oxidation rates and intramyocardial accumulation of lipids. Recent data support the hypothesis that high rates of fatty acid oxidation (e.g. obesity or diabetes) are a major factor contributing to the development of cardiomyopathies.

Сердце является органом с высоким потреблением энергии. Кардиомиоциты постоянно генерируют АТФ, необходимый для мышечного сокращения, поддержания основных метаболических процессов и ионного гомеостаза. В настоящее время считается, что в миокарде около 50-70% АТФ образуется посредством окисления жирных кислот. Целью данного исследования является выяснение особенностей метаболизма жирных кислот в физиологических условиях в миокарде. β-окисление жирных кислот является сложным процессом, который зависит от ряда регулирующих факторов. Транскрипционный контроль ферментов, участвующих в метаболизме жирных кислот и биогенезе митохондрий, является одним из факторов, определяющих скорость β-окисления жирных кислот. Транскрипция ферментов контролируется факторами транскрипции ядерных рецепторов, в том числе PPARs и PGC-1. В миокарде β-окисление жирных кислот является динамическим процессом, который быстро адаптируется к (физиологическим и/или патологическим) изменениям потребления энергии и к окружающей среде. Предыдущие исследования выявили множество противоречивых данных о роли β-окисления жирных кислот во внутрисердечном накоплении липидов. Последние данные подтверждают гипотезу о том, что высокая скорость окисления жирных кислот (например, при ожирении или сахарном диабете) является одним из основных факторов развития кардиомиопатий.

The heart is considered an organ with high-energy demands. Cardiomyocytes permanently generate ATP to maintain contractile function, basal metabolic processes and ionic homeostasis. It is considered that in the myocardium 50-70% of the total ATP is obtained from the fatty acid oxidation. The aim of this study is to elucidate peculiarities of myocardial fatty acid metabolism in physiological conditions. Fatty acid β-oxidation is a complex process dependent upon a number of regulatory factors. The transcriptional control of the enzymes involved in fatty acid metabolism and mitochondrial biogenesis is one of the determinants of the rate of fatty acid β-oxidation. Transcriptional control of the enzymes is regulated by nuclear receptor transcription factors that include PPARs and PGC-1. Cardiac fatty acid β-oxidation is a dynamic process that adapts quickly to the (physiological and/or pathological) changes in cardiac energy demands and changing environment. Previous researches have shown multiple controversial data regarding the fatty acid β-oxidation rates and intramyocardial accumulation of lipids. Recent data support the hypothesis that high rates of fatty acid oxidation (e.g. obesity or diabetes) are a major factor contributing to the development of cardiomyopathies.