Oleogel mitigates inflammation and hepatic steatosis in C57BL/6 mice fed a high-fat high-sucrose diet.

Excessive intake of saturated fats increases the risk of metabolic dysfunction-associated steatotic liver disease. Oleogels are potentially healthier alternatives for saturated fats in food products. This study evaluated the effects of a soybean oil chitosan-based (SOC) oleogel  in adult male C57BL/6 mice. Animals were distributed into 4 groups, according to the diet given for 10 weeks (n=10-14/group, CEUA 017/2023): control (C), control oleogel (CO), high-fat high-sucrose (HFS, containing lard) and high-fat high-sucrose oleogel (HFSO). Body mass and food intake were monitored weekly. Plasma was analyzed for biochemical parameters while epididymal white adipose tissue (eWAT) and liver samples were evaluated by RT-qPCR and stereology. Statistical analysis consisted of one-way ANOVA followed by Tukey’s test (p<0.05). HFSO showed intermediate body mass between C and HFS, with lower body fat mass (-23%;p<0.05) vs HFS. HFSO also showed lower plasma total cholesterol and triglycerides (-35% and -35%; p<0.05), fasting glucose and insulin (-25% and -23%; p<0.05), leptin and Il-6 (-29% and -36%; p<0.05), and ALT and AST (-18% and -34%; p<0.05) vs HFS. Analysis of inflammatory genes in the liver showed lower expression of Tlr4 (-25%;p<0.05), Tnfa (-34%; p<0.05), Il-6 (-50%; p<0.05), and Ccl2 (-46%; p<0.05) in HFSO vs HFS. Regarding hepatic lipid metabolism, Pparg and Srebf1 were lower in HFSO vs HFS (-50% and -54%; p<0.05), with no differences in Acaca and Fasn mRNA expression. The hepatokine Fgf21 was also lower in HFSO vs HFS (-55%; p<0.05). Furthermore, HFS showed mixed steatosis (Vv=57%), fibrosis, and glycogenic degeneration, which were prevented in HFSO. Corroborating these findings, HFSO showed lower gene expression of Col1a1 (-44%; p<0.05) and Casp3 (-47%; p<0.05) vs HFS. Therefore, replacing saturated fat with SOC oleogel ameliorated metabolic and inflammatory parameters and prevented diet-induced hepatic steatosis.