Dietary Flaxseed Oil and Its Blended Oil Alleviate High-Fat Diet-Induced Obesity in Mice by Improving Lipid Metabolism and Regulating Gut Microbiota

Obesity represents a chronic metabolic disorder feature by dysregulated glucose-lipid homeostasis. We investigated the effects of flaxseed oil (FO), rich in α-linolenic acid, and its blended oil (BO) on high-fat diet-induced obese mice. In the BO, the mass ratio of flaxseed oil, sunflower oil (as a source of linoleic acid), and olive oil (as a source of oleic acid) was precisely set at 11.90:51.64:36.46 (<i>w</i>/<i>w</i>/<i>w</i>) After 13 weeks of supplementation, both FO and BO significantly suppressed weight gain (multiple comparisons of weight gain on week 13: 8.57 ± 1.25 g in the ND group; 25.08 ± 2.96 g in the HFD group; 19.35 ± 1.47 g/19.71 ± 2.96 g in the HFD+FO/HFD+BO group), fat accumulation, and restored dyslipidemia (notably, FO administration resulted in a significant reduction in LDL-C and LEP levels (<i>p</i> < 0.01)), elevated blood glucose (FO demonstrated a more pronounced effect compared to BO), and liver tissue damage (specifically, FO exhibited a more pronounced effect in decreasing the levels of oxidative stress markers, including alanine aminotransferase (ALT) and malondialdehyde (MDA), and BO demonstrated greater efficacy in ameliorating the histopathological conditions of liver tissue) in HFD-fed mice. The 16S rRNA gene sequencing of mice fecal samples showed that FO and BO reduced the Firmicutes/Bacteroidetes (F/B) ratio (supplementation with FO decreased the F/B ratio from 68.95 to 15.24 (<i>p</i> < 0.01), while BO supplementation reduced it from 68.95 to 19.47), decreased the abundance of Proteobacteria (supplementation with FO decreased the abundance of Proteobacteria from 0.21 to 0.15, whereas supplementation with BO reduced it to 0.17). In addition, FO increased the abundance of <i>Clostridium</i>, and BO increased the abundance of <i>Lactobacillus</i> (rose from 5.42 to 10.3), reversing the imbalance of gut microbiota in obese mice. These findings suggest that FO and BO may be promising dietary strategies for treating obesity and improving its associated metabolic disorders.