Previous studies have revealed the anti-inflammatory properties of rice bran oil (RBO), but the detailed mechanisms are poorly understood. Recent studies on the molecular/cellular anti-inflammatory mechanisms of dietary components have demonstrated that mitochondrial respiration plays a key role in macrophage functioning. Since dietary lipids are major substrates for mitochondrial respiration through β-oxidation, the current study examined whether RBO regulates inflammatory responses by modulating mitochondrial energy metabolism. Palm oil (PO), enriched with palmitic acid which are known to be effectively taken up by cells and used for oxidative phosphorylation, served as a positive control. In the in vitro model of LPS-stimulated RAW 264.7 murine cells, the levels of pro-inflammatory cytokines (IL-6 and TNF-α) in the culture supernatant were significantly reduced by RBO treatment. In contrast, secretion of the anti-inflammatory cytokine IL-10 was upregulated by RBO. Transcription of genes encoding inflammatory mediator molecules (COX-2 and iNOS) and expression of activation markers (CD80, CD86, and MHC-II) in LPS-stimulated RAW 264.7 cells were suppressed by RBO. Mitochondrial respiration (as assessed by an extracellular flux analyzer) increased upon RBO treatment, as the basal respiration, maximal respiration, ATP production, and spare respiratory capacity were upregulated. In an in vivo study, C57BL/6 mice were fed a negative control diet containing corn oil (CO), PO, or RBO for 4 weeks, and bone marrow-derived macrophages (BMDM) were isolated from their tibias and femurs. In pro-inflammatory M1-polarized BMDM (M1-BMDM), the RBO-induced suppression of IL-6 and TNF-α was recapitulated in vivo. Mitochondrial respiration in M1-BMDM also increased following the RBO intervention and the PO control treatment as compared to CO fed negative control. Overall, the current study for the first time demonstrates that RBO regulates inflammatory responses in murine macrophages by upregulating mitochondrial respiration. Further clinical studies are required to validate the animal study.

The sweetener neohesperidin dihydrochalcone (NHDC) is a precursor for anthocyanins and has been reported to have various bioactivities, including antioxidant and hepatitis inhibitory effects. However, its inflammatory functions and mechanisms of action are poorly understood. In this study, RAW 264.7 murine macrophages were treated with NHDC and its metabolite dihydrocaffeic acid (DHCA), after which cytokine production and mitochondrial respiration were assessed. DHCA significantly down-regulated the secretion of pro-inflammatory cytokines. In contrast, NHDC had a marginal effect, suggesting that the biological metabolism of NHDC to DHCA is required for its anti-inflammatory function. However, both NHDC and DHCA rescued LPS-induced suppression of oxidative phosphorylation, which is a hallmark of anti-inflammatory M2 macrophages. 3T3-L1 adipocytes showed lower fat deposition in the presence of DHCA, while sugar-containing NHDC showed a slight increase in fat deposition. In high-fat diet-induced obese mice, treatment with NHDC successfully down-regulated body weight gain in a dose-dependent manner. Furthermore, M2 polarized bone-marrow-derived macrophages (BMDM) from NHDC-fed mice secreted an increased amount of the anti-inflammatory cytokine IL-10. Overall, these results indicate that NHDC and its physiological metabolite DHCA have the potential to suppress the inflammatory response and obese status.

Medium chain triglyceride (MCT) oil has been postulated to modulate inflammatory responses, but the detailed mechanisms have not been fully elucidated. Based on recent studies demonstrating that mitochondrial metabolic reprogramming and immune responses are correlated, the current study sought to determine whether MCT oil controls inflammatory responses through modulation of mitochondria using both in vitro and in vivo models. The mitochondrial metabolic phenotypes of macrophages were assessed according to oxygen consumption rate (OCR). Inflammatory responses were assessed for production of cytokines and expression of activation markers. MCT oil was more rapidly oxidized as observed by increased OCR in macrophages. The production of pro-inflammatory cytokines was down-regulated and anti-inflammatory cytokine was elevated by MCT oil. In addition, classically activated M1 and alternatively activated M2 markers were reciprocally regulated by MCT intervention. Overall, up-regulated β-oxidation by MCT contributes to the anti-inflammatory M2-like status of macrophages, which may aid in the dietary prevention and/or amelioration of inflammation.

Studies reported the beneficial effects of trehalose on metabolic syndromes, hyperlipidemia, and autophagy, but its action mechanisms are still poorly understood. Even though trehalose is digested by disaccharidase and absorbed in the intestine, intact molecules encounter immune cells which form a solid balance between the allowance of nutritive substances and the removal of harmful pathogens. In this regard, the polarization of intestinal macrophages into an anti-inflammatory phenotype through metabolic regulation is emerging as a therapeutic strategy for the prevention of gastrointestinal inflammation. The current study investigated the effects of trehalose on immunological phenotypes, energy metabolism, and LPS-induced macrophage mitochondrial functioning. Results indicate that trehalose reduces prostaglandin E₂ and nitric oxide, which are inflammatory mediators of LPS-induced macrophages. In addition, trehalose further significantly suppressed inflammatory cytokines and mediators via energy metabolism reprogramming towards M2-like status in LPS-stimulated macrophages.

Dietary approaches using structured lipids, including medium-chain fatty acids and diacylglycerols, have been adopted for the prevention of obesity-induced chronic inflammation. In an extension to previous studies, medium-chain fatty acid-diacylglycerol enriched dietary oil (MCDG) was prepared by interesterification of canola oil and mediumchain fatty acid-triacylglycerols. The consequent MCDG product was applied to RAW264.7 macrophages followed by the assessment of multiple inflammatory responses. Compared with conventionally used canola and olive oil controls, MCDG suppressed macrophage phagocytosis, as assessed by the uptake of microsphere beads. Furthermore, the production of IL-6 and TNF-α, transcription of COX-2 and iNOS, and expression of CD80 on cell surfaces were downregulated by MCDG in LPS-stimulated macrophages. Subsequently, differentiated 3T3-L1 adipocytes were evaluated for proinflammatory cytokine production and lipid accumulation. IL-6 production was marginally affected and lipid accumulation was inhibited by MCDG. Taken together, these results suggest that MCDG has potential as an alternative oil for cooking in order to prevent obesity-induced inflammation.

Macrophages are involved in all inflammatory processes from killing pathogens to repairing damaged tissue. In the obese state, macrophages infiltrate into enlarged adipose tissue and polarize into pro-inflammatory M1 macrophages, resulting in chronic low-grade inflammation due to the secretion of inflammatory mediators. Rice bran oil (RBO) is an edible oil containing tocopherols, tocotrienols, and γ-oryzanol. Previous research in normal diet-fed mice suggested that RBO mitigates inflammatory responses by modulating mitochondrial respiration of macrophages. Therefore, we investigated if RBO had an anti-inflammatory effect in diet-induced obese mice by assessing the expression of inflammatory markers in epididymal white adipose tissue (eWAT) and polarization of bone marrow-derived macrophages (BMDMs). Rice bran oil exerted a local anti-inflammatory effect in white adipose tissue by suppressing the production of inflammatory mediators and upregulating transcription of anti-inflammatory genes. Rice bran oil also promoted anti-inflammatory M2 macrophage polarization in BMDMs thereby affecting systemic inflammation. Overall, our in vivo and ex vivo results highlight the potential of RBO as a dietary mediator that can ameliorate obesity-induced chronic low-grade inflammation by mediating the expression of inflammation-related factors and macrophage polarization.