Metabolomic Analysis of Diet-Induced Obese Mice Supplemented with Eicosapentaenoic Acid

Abstract

Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with anti-inflammatory effects. To determine the effects of EPA on metabolic pathways in obese adipose tissues and liver, mice were fed normal chow diet (NCD), high-fat diet (HFD), or 3% EPA-containing high fat diet (HFD+EPA) for 8 weeks. Metabolomic analysis was performed using epididymal adipose tissues (epi WAT) and liver. Metabolites that were specifically elevated in HFD+EPA, were assessed for their anti-inflammatory properties using RAW264.7 macrophage cells. Body and adipose tissue weights were significantly higher in HFD than NCD, and lower in HFD+EPA than HFD. Plasma insulin levels were significantly higher in HFD than NCD, and lower in HFD+EPA compared with HFD. Plasma monocyte chemotactic protein-1 (MCP-1) levels were higher in HFD than NCD, and tended to be lower in HFD+EPA than HFD. The levels of intermediate metabolites in the glycolytic pathways were lower in HFD compared with NCD and HFD+EPA in both epi WAT and liver, while intermediate metabolites of the TCA cycles were elevated in HFD and HFD+EPA compared with NCD in epi WAT. Among the metabolites in epi WAT, the levels of thiaproline, phenaceturic acid, and pipecolic acid were specifically elevated in HFD+EPA, but not in HFD or NCD. Treatment of RAW264.7 cells with thiaproline significantly ameliorated LPS-induced iNOS expression, while pipecolic acid inhibited LPS-induced IL-1β expression. These results suggest that EPA normalizes glycolytic pathway intermediates in both epi WAT and liver, and induces metabolites with anti-inflammatory properties.

Integrated analysis of gut microbiome and its metabolites in ACE2-knockout and ACE2-overexpressed mice

“…These metabolites have been identified as MetS-linked metabolites involved with lipid accumulation and reduced gut bacterial load ( Wang et al., 2015 ; Tan et al., 2023 ). Importantly, the metabolites, such as pipecolic acid, L-phenylalanine, taurocholic acid, serotonin, D-serine, and guggulsterone, have been proven to have anti-inflammatory actions and possess anorexic and hypoglycemic properties ( Lam and Heisler, 2007 ; Yamada and Sugimoto, 2016 ; Cheng et al., 2018 ; Nishitani et al., 2018 ; Lockridge et al., 2021 ; Osuga et al., 2022 ). Elevated levels of these metabolites in ACE2-overexpressed mice might suppress the appetite and lipid deposition and enhance GLP-1 secretion, resulting in restored glucose and lipid metabolism disorder.…”

Evaluation of the amelioration effect of Ganoderma formosanum extract on delaying PM2.5 damage to lung macrophages

“…In the context of metabolomics from diet-induced obese mice supplemented with eicosapentaenoic acid, pipecolic acid was observed to inhibit LPS-induced IL-1𝛽 expression, effectively downregulating inflammation. [56,57] Acetyl-L-carnitine can enhance antioxidant capacity in mice and reduce the release of TNF-𝛼 and COX-2 induced by LPS by suppressing the NF-𝜅B pathway. [58] D-Mannitol inhibits IKK protein activity, prevents activation of the NF-𝜅B pathway, and shows potential for treating NF-𝜅B pathway related diseases.…”

The serum metabolic profile plays a role in mediating the regulatory impact of gut microbiota and its metabolites on susceptibility to obesity in mice

“…Additionally, TC, HDL, LDL, and adipocyte area were inversely associated with Corticosterone and 9,10-Dihome (P < 0.05). Metabolites such as AA, EPA, DHA, and HA have been identi ed as potentially connected to obesity (Nishitani et al, 2020;Zhang et al, 2023b;Zhuang et al, 2020). AA is thought to contribute to insulin resistance and subsequent obesity, while EPA and DHA, as unsaturated fatty acids, are recognized for their antiin ammatory and anti-obesity properties.…”