Rennie Claire, Donnelly Sheila, McGrath Kristine
School of Life Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Australian Institute for Microbiology and Infection, University of Technology Sydney, Sydney, NSW 2007, Australia.
Int J Mol Sci. 2025 Jul 24;26(15):7156. doi: 10.3390/ijms26157156.
There are currently no approved therapeutic treatments targeting metabolic dysfunction-associated steatotic liver disease (MASLD). Albumin, a liver-produced plasma protein with anti-inflammatory and antioxidant properties, is reduced in advanced liver disease. Considering the role of chronic obesity-induced inflammation in MASLD pathogenesis, we investigated whether albumin administration could prevent disease progression to metabolic dysfunction-associated steatohepatitis (MASH). MASLD was induced in mice using a high-fat and high-cholesterol (PC) treatment for 8 weeks, followed by treatment with bovine serum albumin (BSA; 0.8 mg/kg) every three days for another 8 weeks. This regimen prevented time-dependent weight gain, regardless of diet, with 57% and 27% reductions in mice fed a standard chow (Std Chow) or PC diet, respectively. Further, supplementation reduced nuclear factor kappa B (NF-κB) activation by 2.8-fold ( = 0.0328) in PC-fed mice, consistent with albumin's known anti-inflammatory properties. Unexpectedly, albumin also reduced hepatic neutral lipid accumulation and circulating non-esterified fatty acids. While PC-fed mice did not exhibit full progression to MASH, albumin treatment significantly increased hepatic matrix metalloproteinase-2 expression, suggesting the inhibition of early fibrotic signalling. While further studies are needed to elucidate the underlying mechanisms, these findings offer new insight into the potential of albumin, either alone or in combination with other therapies, to reduce hepatic steatosis in MASLD.
目前尚无针对代谢功能障碍相关脂肪性肝病（MASLD）的获批治疗方法。白蛋白是一种由肝脏产生的具有抗炎和抗氧化特性的血浆蛋白，在晚期肝病中含量会降低。考虑到慢性肥胖诱导的炎症在MASLD发病机制中的作用，我们研究了给予白蛋白是否可以预防疾病进展为代谢功能障碍相关脂肪性肝炎（MASH）。采用高脂高胆固醇（PC）饮食喂养小鼠8周以诱导MASLD，随后每隔三天给予牛血清白蛋白（BSA；0.8 mg/kg）再治疗8周。无论饮食如何，该方案均能预防体重随时间增加，喂食标准饲料（Std Chow）或PC饮食的小鼠体重分别降低了57%和27%。此外，补充白蛋白使喂食PC饮食的小鼠中核因子κB（NF-κB）的激活降低了2.8倍（P = 0.0328），这与白蛋白已知的抗炎特性一致。出乎意料的是，白蛋白还减少了肝脏中性脂质积累和循环中非酯化脂肪酸的含量。虽然喂食PC饮食的小鼠并未完全进展为MASH，但白蛋白治疗显著增加了肝脏基质金属蛋白酶-2的表达，提示早期纤维化信号受到抑制。虽然需要进一步研究来阐明潜在机制，但这些发现为白蛋白单独或与其他疗法联合使用以减少MASLD中的肝脏脂肪变性的潜力提供了新的见解。
