Amino Acid Is A Major Carbon Source For Hepatic Lipogenesis Yilie Liao Qishan Chen Lei Liu Haipeng Huang Jingyun Sun Xiaojie Bai Chenchen Jin Honghao Li Fangfang Sun Xia Xiao Yahong Zhang Jia Li Weiping Han Suneng Fu by Yilie Liao & Qishan Chen & Lei Liu & Haipeng Huang & Jingyun Sun & Xiaojie Bai & Chenchen Jin & Honghao Li & Fangfang Sun & Xia Xiao & Yahong Zhang & Jia Li & Weiping Han & Suneng Fu 101016/JCMET202410001 instant download after payment.

SUMMARYIncreased de novo lipogenesis is a hallmark of metabolic dysfunction-associated steatotic liver disease(MASLD) in obesity, but the macronutrient carbon source for over half of hepatic fatty acid synthesis remainsundetermined. Here, we discover that dietary protein, rather than carbohydrates or fat, is the primary nutritional risk factor for MASLD in humans. Consistently, ex vivo tracing studies identify amino acids as a majorcarbon supplier for the tricarboxylic acid (TCA) cycle and lipogenesis in isolated mouse hepatocytes. In vivo,dietary amino acids are twice as efficient as glucose in fueling hepatic fatty acid synthesis. The onset ofobesity further drives amino acids into fatty acid synthesis through reductive carboxylation, while geneticand chemical interventions that divert amino acid carbon away from lipogenesis alleviate hepatic steatosis.Finally, low-protein diets (LPDs) not only prevent body weight gain in obese mice but also reduce hepatic lipidaccumulation and liver damage. Together, this study uncovers the significant role of amino acids in hepaticlipogenesis and suggests a previously unappreciated nutritional intervention target for MASLD.