Microalgae Oil Attenuates Liver Fat Deposition in NAFLD via Modulation of Anti-Lipogenic Genes and Insulin Signaling...

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver-related mortality and morbidity globally, with its prevalence steadily rising. DHA-rich fish oil has demonstrated potential in managing NAFLD. However, little is known about the effect of pure DHA extracted from microalgae oil. This study explored the influence DHA-rich microalgae oil might have on genes and metabolites associated with lipid and glucose metabolism in NAFLD mice, offering promising insights into a novel, cost-effective treatment for NAFLD. In this study, C57BL/6J mice (n = 15) were used. NAFLD mice model was established by feeding mice HFD. Microalgae oil (10 μL/g body weight) was administered daily by oral gavage to HFD-induced NAFLD mice (n = 5), while control mice and untreated HFD mice (n = 5 per group) received an equivalent volume of saline. Body weight was monitored regularly, and blood samples were collected to measure serum glucose and lipid levels. Tissue samples were analyzed using H&E staining and Oil Red O staining to assess histological changes. Differentially expressed genes and metabolites were identified through enrichment analyses. Microalgae oil supplementation showed a potential effect in reducing hepatic fat accumulation in NAFLD mice. The increase in liver weight induced by HFD was partially reduced by 7% in microalgae oil-treated mice. Moreover, microalgae oil partially restored 10% of the HFD-induced loss in muscle mass and decreased white adipose tissue depots by an average of 39.3%. Treatment significantly lowered serum total cholesterol (from 4.39 to 3.57 mmol/L) and LDL-c (from 0.98 to 0.63 mmol/L), while ameliorating hepatic enlargement and the elevation of liver enzymes (AST, ALT). RNA sequencing revealed that 79.8% of HFD-upregulated genes were potentially downregulated by microalgae oil, particularly those related to glucose and lipid metabolism. Furthermore, microalgae oil treatment was associated with a downregulation of the PPAR and PI3K-Akt signaling pathways, which were found to be enriched in the HFD-fed group. Upregulation of Irs1 and suppression of Saa2 might suggest enhanced glucose uptake and reduced inflammation. Metabolomic analyses, including MSEA and OPLS-DA, suggested that microalgae oil intervention may modulate the abundance of various carbohydrates and fatty acids. Collectively, these findings indicate that DHA-enriched microalgae oil might aid in alleviating HFD-induced metabolic and inflammatory disturbances in NAFLD. In conclusion, DHA-enriched microalgae oil might exert a positive regulatory effect on genes and metabolites governing lipid and glucose metabolism. The findings from this study may provide a foundation for the development of a beneficial and cost-effective microalgae oil as a potential therapeutic strategy. However, although the HFD-induced NAFLD model recapitulates several features of human disease, it does not fully capture the complexity and heterogeneity of NAFLD in humans. The dosing regimen, involving a single dose administered via oral gavage, may not directly translate to typical human intake patterns, where intake occurs through diet and may influence absorption and metabolic responses. While beneficial effects were observed, the underlying molecular mechanisms require further investigation.