Bempedoic acid suppresses diet-induced hepatic steatosis independently of ATP-citrate lyase.

ATP citrate lyase (ACLY) synthesizes acetyl-CoA for de novo lipogenesis (DNL), which is elevated in metabolic dysfunction-associated steatotic liver disease. Hepatic ACLY is inhibited by the LDL-cholesterol-lowering drug bempedoic acid (BPA), which also improves steatosis in mice. While BPA potently suppresses hepatic DNL and increases fat catabolism, it is unclear if ACLY is its primary molecular target in reducing liver triglyceride.

Review of per- and poly-fluoroalkyl treatment in combustion-based thermal waste systems in the United States.

Per- and poly-fluoroalkyl substances (PFAS) are a class of synthetic chemicals known for their widespread presence and environmental persistence. Carbon-fluorine (C-F) bonds are major components among PFAS and among the strongest organic bonds, thus destroying PFAS may present significant challenge. Thermal treatment such as incineration is an effective and approved method for destroying many halogenated organic chemicals.

αKG-mediated carnitine synthesis promotes homologous recombination via histone acetylation.

Homologous recombination (HR) deficiency enhances sensitivity to DNA damaging agents commonly used to treat cancer. In HR-proficient cancers, metabolic mechanisms driving response or resistance to DNA damaging agents remain unclear. Here we identified that depletion of alpha-ketoglutarate (αKG) sensitizes HR-proficient cells to DNA damaging agents by metabolic regulation of histone acetylation.

Lactoylglutathione promotes inflammatory signaling in macrophages through histone lactoylation.

Chronic, systemic inflammation is a pathophysiological manifestation of metabolic disorders. Inflammatory signaling leads to elevated glycolytic flux and a metabolic shift towards aerobic glycolysis and lactate generation. This rise in lactate corresponds with increased generation of lactoylLys modifications on histones, mediating transcriptional responses to inflammatory stimuli.