GCN5 acetyltransferase in cellular energetic and metabolic processes

Metabolic syndrome is widespread and negatively impacts healthy longevity but takes years to study in mammalian models, delaying translational applications. To address this, we characterized the unique polygenic "Titan" mouse (110 grams average) with a healthy lifespan of only 4 months that was generated by 45 years of breeding selection. Titan mice displayed increased plasma leptin, insulin, IL-6 and fasting triglycerides. Also, pancreatic fat cell accumulation and thymic medullary hyperplasia were detected in Titan animals. Liver transcriptome and proteome analysis demonstrated alterations in lipid metabolism, the methionine cycle, and cytochrome P450 regulation in Titan mice. Late dietary intervention in Titan mice reduced fat content and improved expression of genes involved in lipid synthesis and cytochrome P450 detoxification, altering the abundance of metabolites, including malonyl-CoA and dimethylglycine. Strikingly, late dietary intervention at 3 months of age almost doubled the healthy lifespan of Titan mice. This powerful model of metabolic disorders, systemic inflammation, and early aging will enable to provide uniquely rapid results for translational intervention.

Endothelial cell (EC), consisting of the innermost cellular layer of all types of vessels, is not only a barrier composer but also performing multiple functions in physiological processes. It actively controls the vascular tone and the extravasation of water, solutes, and macromolecules; modulates circulating immune cells as well as platelet and leukocyte recruitment/adhesion and activation. In addition, EC also tightly keeps coagulation/fibrinolysis balance and plays a major role in angiogenesis. Therefore, endothelial dysfunction contributes to the pathogenesis of many diseases. Growing pieces of evidence suggest that histone protein acetylation, an epigenetic mark, is altered in ECs under different conditions, and the acetylation status change at different lysine sites on histone protein plays a key role in endothelial dysfunction and involved in hyperglycemia, hypertension, inflammatory disease, cancer and so on. In this review, we highlight the importance of histone acetylation in regulating endothelial functions and discuss the roles of histone acetylation across the transcriptional unit of protein-coding genes in ECs under different disease-related pathophysiological processes. Since histone acetylation changes are conserved and reversible, the knowledge of histone acetylation in endothelial function regulation could provide insights to develop epigenetic interventions in preventing or treating endothelial dysfunction-related diseases.

As the earliest studied epigenetic modification, acetylation has been explored a lot through the years. While bone tissue acts as an indispensable part of body, researches aimed at the relationship between the bone and acetylation became necessary. Some environmental factors like diet may affect the metabolism status that some metabolites especially nicotinamide adenine dinucleotide (NAD) were found able to regulate intracellular histone acetylation in bone metabolism. This review focuses on representing the interaction among acetylation, metabolism, and the bone. The results showed that acetylation connects a lot with bone metabolism, while the explorations about related metabolites like acetyl-CoA or different environmental exposures are still limited. Some acetylation-related therapy methods of bone diseases based on metabolic regulation or epigenetic enzymes were also reviewed.