Chaetoceros gracilis, a marine microalga, attenuates hepatic lipid accumulation in SDT fatty rats, a severe genetic MASLD model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with metabolic syndrome and is characterized by excessive accumulation of hepatic li-pids. Marine microalgae have attracted increasing attention as sustainable sources of bioactive lipids. We previously demonstrated that dietary supplementation with the marine microalga Chaetoceros gracilis (Chaeto) attenuated hepatic lipid accumulation in high-sucrose- and cholesterol-fed Sprague-Dawley rats. The present study examined whether these li-pid-modulating effects in the diet-induced model are preserved in Spontaneously Diabetic Torii (SDT) fatty rats, a severe, genetic model exhibiting MASLD-like features, to evaluate the ro-bustness and broader applicability of Chaeto across different MASLD conditions. Male SDT fatty rats were fed a control diet or a diet supplemented with 5 % (w/w) Chaeto for 5 weeks. Hepatic lipid content, plasma lipid profiles, fecal lipid excretion, and hepatic enzyme activities and gene expression related to lipid metabolism were analyzed. Chaeto supplementation sig-nificantly reduced hepatic triglyceride and cholesterol content compared with that of the Control group that was fed a non-supplemented diet. Hepatic fatty acid synthesis was suppressed at both enzymatic and transcriptional levels, whereas carnitine palmitoyltransferase activity was in-creased, indicating enhanced β-oxidation of fatty acids. The reduction in hepatic cholesterol levels was associated with decreased expression of cholesterol synthesis-and esterification-related genes and increased fecal neutral steroid excretion, while fecal acidic steroid excretion remained un-changed. Plasma non-high-density lipoprotein triglyceride and cholesterol concentrations were significantly reduced without aggravating hypercholesterolemia. Collectively, these findings demonstrate that Chaeto exerts robust lipid-modulating effects even under severe meta-bolic conditions that are genetically based. Suppression of hepatic fatty acid synthesis appears to be a shared mechanism when comparing the genetic and diet-based models, whereas enhancement of fatty acid β-oxidation was specifically evident in the former. Thus, Chaeto may be a promising marine lipid resource for the management of hepatic lipid disorders.