Beyoğlu Diren, Popov Yury V, Idle Jeffrey R
Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA 01119, USA.
Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Int J Mol Sci. 2024 Nov 28;25(23):12809. doi: 10.3390/ijms252312809.
From a detailed review of 90 experimental and clinical metabolomic investigations of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), we have developed metabolomic hallmarks for both obesity and MASLD. Obesity studies were conducted in mice, rats, and humans, with consensus biomarker groups in plasma/serum being essential and nonessential amino acids, energy metabolites, gut microbiota metabolites, acylcarnitines and lysophosphatidylcholines (LPC), which formed the basis of the six metabolomic hallmarks of obesity. Additionally, mice and rats shared elevated cholesterol, humans and rats shared elevated fatty acids, and humans and mice shared elevated VLDL/LDL, bile acids and phosphatidylcholines (PC). MASLD metabolomic studies had been performed in mice, rats, hamsters, cows, geese, blunt snout breams, zebrafish, and humans, with the biomarker groups in agreement between experimental and clinical investigations being energy metabolites, essential and nonessential amino acids, fatty acids, and bile acids, which lay the foundation of the five metabolomic hallmarks of MASLD. Furthermore, the experimental group had higher LPC/PC and cholesteryl esters, and the clinical group had elevated acylcarnitines, lysophosphatidylethanolamines/phosphatidylethanolamines (LPE/PE), triglycerides/diglycerides, and gut microbiota metabolites. These metabolomic hallmarks aid in the understanding of the metabolic role played by obesity in MASLD development, inform mechanistic studies into underlying disease pathogenesis, and are critical for new metabolite-inspired therapies.
通过对90项肥胖与代谢功能障碍相关脂肪性肝病（MASLD）的实验和临床代谢组学研究进行详细回顾，我们得出了肥胖和MASLD的代谢组学特征。肥胖研究在小鼠、大鼠和人类中进行，血浆/血清中的共识生物标志物组包括必需和非必需氨基酸、能量代谢物、肠道微生物群代谢物、酰基肉碱和溶血磷脂酰胆碱（LPC），这些构成了肥胖的六个代谢组学特征的基础。此外，小鼠和大鼠的胆固醇升高，人类和大鼠的脂肪酸升高，人类和小鼠的极低密度脂蛋白/低密度脂蛋白、胆汁酸和磷脂酰胆碱（PC）升高。MASLD代谢组学研究已在小鼠、大鼠、仓鼠、牛、鹅、团头鲂、斑马鱼和人类中进行，实验和临床研究一致的生物标志物组为能量代谢物、必需和非必需氨基酸、脂肪酸和胆汁酸，这些奠定了MASLD的五个代谢组学特征的基础。此外，实验组的LPC/PC和胆固醇酯较高，临床组的酰基肉碱、溶血磷脂酰乙醇胺/磷脂酰乙醇胺（LPE/PE）、甘油三酯/甘油二酯和肠道微生物群代谢物升高。这些代谢组学特征有助于理解肥胖在MASLD发展中所起的代谢作用，为潜在疾病发病机制的机制研究提供信息，并且对于新的基于代谢物的疗法至关重要。
