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<p>The enzyme 5ʹ-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism, playing a protective role in cardiovascular remodeling and diseases. Here, 1,1-Diethoxyethane (1,1-DEE; Biosacetalin), a compound traditionally known as a flavoring agent in wine and distilled spirits, was identified as an AMPK activator. By analyzing AC16 cardiomyocytes with the Seahorse Mito Stress Test, we found that 1,1-DEE induced a transient inhibition of both mitochondrial respiration and glycolysis, resulting in reduced ATP production. This metabolic disturbance triggered AMPK activation in a time- and concentration-dependent manner, leading to adaptive increases in the phosphorylation of acetyl-CoA carboxylase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2, which promotes fatty acid oxidation and glycolysis. AMPK activation also enhanced mitochondrial biogenesis by upregulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial transcription factor A. These alterations led to a sustained increase in both mitochondrial respiration and glycolysis. Overall, our findings unravel the important physiological role of 1,1-DEE in energy homeostasis through AMPK activation and aerobic respiration. This mechanism may hold therapeutic potential for the prevention and treatment of metabolic and cardiovascular diseases.</p>

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1,1-Diethoxyethane enhances aerobic respiration in human mitochondria via activation of AMP-activated protein kinase

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月3日

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  • Thang Nguyen Huu,
  • Hien Duong Thanh,
  • Min-Kyu Kim,
  • Dhiraj Kumar Sah,
  • Vu Hoang Trinh,
  • Hyun Joong Yoon,
  • Jin Myung Choi,
  • Geun-Haeng Lee,
  • Seon-Young Kim,
  • Seung-Rock Lee

摘要

The enzyme 5ʹ-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism, playing a protective role in cardiovascular remodeling and diseases. Here, 1,1-Diethoxyethane (1,1-DEE; Biosacetalin), a compound traditionally known as a flavoring agent in wine and distilled spirits, was identified as an AMPK activator. By analyzing AC16 cardiomyocytes with the Seahorse Mito Stress Test, we found that 1,1-DEE induced a transient inhibition of both mitochondrial respiration and glycolysis, resulting in reduced ATP production. This metabolic disturbance triggered AMPK activation in a time- and concentration-dependent manner, leading to adaptive increases in the phosphorylation of acetyl-CoA carboxylase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2, which promotes fatty acid oxidation and glycolysis. AMPK activation also enhanced mitochondrial biogenesis by upregulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial transcription factor A. These alterations led to a sustained increase in both mitochondrial respiration and glycolysis. Overall, our findings unravel the important physiological role of 1,1-DEE in energy homeostasis through AMPK activation and aerobic respiration. This mechanism may hold therapeutic potential for the prevention and treatment of metabolic and cardiovascular diseases.