Obesity is a global health concern, leading to metabolic disorders like dyslipidemia and insulin resistance. ω-3 polyunsaturated fatty acids (PUFAs) from both marine (e.g., fish oil, FO) and plant (e.g., perilla oil, PO) sources have shown promise in improving metabolic health. While both FO and PO are rich in ω-3 PUFAs, their comparative effects and underlying mechanisms remain unclear. Previous research has highlighted the role of ω-3 PUFAs in vascular health and the reduction of triglycerides in patients with hypertriglyceridemia. Furthermore, dietary ω-3 PUFAs have been recommended for managing type 2 diabetes. However, inconsistencies exist in the literature regarding the relative efficacy of marine versus plant-based ω-3 PUFAs. The study aims to compare the effects of FO and PO on glucolipid metabolism, inflammation, and adipokine levels in mice fed a high-fat diet, focusing on the role of the TLR4/MyD88 signaling pathway. Understanding the mechanisms by which ω-3 PUFAs exert their beneficial effects is crucial for developing effective strategies to combat obesity and related metabolic diseases. The TLR4 pathway, highly expressed in adipocytes, plays a significant role in obesity-induced inflammation. This study investigates the MyD88-dependent and -independent pathways of TLR4 signaling to determine which pathway is responsible for the protective effects of ω-3 PUFAs.

Existing literature shows conflicting results on the comparative efficacy of marine and plant ω-3 PUFAs. Some studies demonstrate similar benefits of both sources in reducing hypercholesterolemia and improving insulin sensitivity. Others highlight differences, with FO showing greater efficacy in reducing triglycerides in some populations. The variability might be attributed to factors such as oil type, animal models used, and the presence of other co-morbidities. The ratio of ω-3 to ω-6 PUFAs is also a critical factor influencing metabolic outcomes. There is evidence suggesting that the ratio of ω-3 to ω-6 PUFAs, rather than the total amount of ω-3 PUFAs alone, may be more important for metabolic health. Further research is needed to clarify the differential effects of ω-3 PUFAs from different sources on metabolic health and their interactions with other dietary components.

The study used male C57BL/6J mice and MyD88-/- mice, randomly assigned to four groups: normal chow diet (NC), high-fat diet (HF), HF diet with FO supplementation, and HF diet with PO supplementation. After four weeks, various parameters were measured. Blood samples were analyzed for glucose, triglycerides, total cholesterol, HDL-C, LDL-C, insulin, MCP-1, IL-6, TNF-α, leptin, and resistin. Adipocyte histology was assessed using hematoxylin and eosin staining. Gene expression of TLR4, MyD88, TRAF6, IKKβ, RIP1, IRF3, and NF-κB p65 in epididymal adipose tissue was analyzed using real-time quantitative PCR and Western blotting. Statistical analysis was performed using two-tailed one-way ANOVA followed by Tukey's post hoc test. The sample size was determined based on previous studies.

In C57BL/6J mice, both FO and PO significantly reduced body weight, glucose, insulin, triglycerides, total cholesterol, and IL-6 levels compared to the HF group. Both oils also decreased the mRNA and protein expression of TLR4, MyD88, TRAF6, and IKKβ. In MyD88-/- mice, the beneficial effects of FO and PO on metabolic parameters and inflammation were abolished. FO and PO did not significantly affect the mRNA and protein expression of RIP1, IRF3, and NF-κB p65 in MyD88-/- mice. These findings indicate that the protective effects of FO and PO are primarily mediated through the MyD88-dependent pathway of TLR4 signaling. While FO and PO exhibited similar overall effects on metabolic parameters, some differences in HDL-C and LDL-C levels were observed between the two groups. These subtle differences might be indicative of variations in HDL particle quality and composition which require further investigation using appropriate analytical techniques.

The findings of this study demonstrate that both fish oil and perilla oil exert similar protective effects against metabolic disorders and inflammation in mice fed a high-fat diet. This protective effect is primarily mediated through the MyD88-dependent pathway of TLR4 signaling. The study confirms the effectiveness of plant-based ω-3 PUFAs as an alternative to marine-based ω-3 PUFAs. The study also reveals the crucial role of the MyD88 pathway in mediating the anti-inflammatory and metabolic benefits of ω-3 PUFAs. Future research could focus on clarifying the underlying mechanisms involved in the modulation of TLR4 signaling by ω-3 PUFAs and further characterizing the differences between marine and plant-based sources in terms of their effects on HDL subfractions. It is crucial to consider factors like the ratio of ω-3 to ω-6 PUFAs and individual variations in response to ω-3 PUFAs.

This study shows that fish oil and perilla oil similarly protect against metabolic disorders and inflammation by inhibiting MyD88-dependent TLR4 signaling. Plant ω-3 PUFAs are a promising alternative to marine ω-3 PUFAs. Further research should investigate dose-response relationships and the specific mechanisms of action to enhance understanding and optimize the use of ω-3 PUFAs in preventing metabolic diseases.

One limitation is the difference in the dosage regimen of EPA+DHA and ALA. The study used a single dose and time point, limiting the assessment of dose-effect and time-effect relationships. Future studies should address these issues to obtain a more comprehensive understanding of the comparative effects of various ω-3 PUFA sources. Another limitation involves the use of only two oil types, and the conclusions may not be broadly generalizable to all types of marine and plant ω-3 PUFAs.