In addition to their use in relieving the symptoms of various diseases,ketogenic diets(KDs)have also been adopted by healthy individuals to prevent being overweight.Herein,we reported that prolonged KD exposure induce...In addition to their use in relieving the symptoms of various diseases,ketogenic diets(KDs)have also been adopted by healthy individuals to prevent being overweight.Herein,we reported that prolonged KD exposure induced cardiac fibrosis.In rats,KD or frequent deep fasting decreased mitochondrial biogenesis,reduced cell respiration,and increased cardiomyocyte apoptosis and cardiac fibrosis.Mechanistically,increased levels of the ketone body β-hydroxybutyrate(β-OHB),an HDAC2 inhibitor,promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription.This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis,leading to cardiomyocyte apoptosis and cardiac fibrosis.展开更多
基金supported by the Grants from the State Key Development Programs of Basic Research of China(Nos.2019YFA0801900,2018YFC100242,2018YFA080030,2018YFA0801300,and 2018YFC1004700)the National Natural Science Foundation of China(Nos.31871432,81771627,31521003,31821002,91753207,81722021,81471454,31671483,31671453,and 31425008)。
文摘In addition to their use in relieving the symptoms of various diseases,ketogenic diets(KDs)have also been adopted by healthy individuals to prevent being overweight.Herein,we reported that prolonged KD exposure induced cardiac fibrosis.In rats,KD or frequent deep fasting decreased mitochondrial biogenesis,reduced cell respiration,and increased cardiomyocyte apoptosis and cardiac fibrosis.Mechanistically,increased levels of the ketone body β-hydroxybutyrate(β-OHB),an HDAC2 inhibitor,promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription.This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis,leading to cardiomyocyte apoptosis and cardiac fibrosis.
