Rice bran oil ameliorates inflammatory responses by enhancing mitochondrial respiration in murine macrophages

Abstract

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.

Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine

“…Hence, the carnosine activity on NO, leading to increase nitrite, would not cause any adverse effect but might rather represent an additional positive pharmacological effect of this natural compound. Previous studies, using 500 ng/mL of LPS [66] or 1000 ng/mL LPS [67] to stimulate macrophages, showed significant changes in energy metabolism and mitochondrial functions. In the present study, using five and 10 times lower LPS concentrations than those used in the aforementioned studies, we found that 100 ng/mL LPS was sufficient to significantly perturb the energy and redox metabolism of macrophages (Figures 3 and 4), whilst being completely free of any cytotoxic effect.…”

Rice Bran Oil Attenuates Chronic Inflammation by Inducing M2 Macrophage Switching in High-Fat Diet-Fed Obese Mice

“…Regulation of chronic inflammation through switching the macrophage phenotype using dietary components is of growing interest. A prior study demonstrated that rice bran oil (RBO) had anti-inflammatory effects by regulating mitochondrial respiration of macrophages in a normal diet-fed mice model [ 27 ]. Therefore, in the current study, we evaluated the anti-inflammatory effects of rice bran oil in a high-fat diet-induced obese mouse model by performing in vivo and ex vivo experiments.…”

“…Rice bran oil has previously been shown to attenuate obesity, hyperlipidemia, and inflammation in mice and rats [ 25 , 26 , 44 ]. A previous study also demonstrated that RBO exerted its anti-inflammatory effects through modulating the mitochondrial respiration of macrophages in normal diet-fed mice [ 27 ]. In this regard, there is a lack of data regarding the effects of palm oil on local chronic inflammation and macrophage polarization in high-fat diet-induced obese mouse models.…”

“…The fat composition of each experimental diet was modified by replacing lard with rice bran oil (RBO) or palm oil (PO) as shown in Table 1 . Commercially available RBO and PO were purchased from Serim Hyunmi (Jungeup-si, Korea) and JCY (Seongnam-si, Korea) [ 27 ]. Following 1 week of acclimation, mice were randomly divided into four groups ( n = 6–8) and received the specified diet and water ad libitum for 10 weeks.…”

“…Previous studies have demonstrated that RBO not only alleviates hyperglycemia and hyperlipidemia but also exhibits anti-oxidant and immunomodulatory effects [ 22 , 23 , 24 , 25 , 26 ]. Recently, it was demonstrated that RBO exerts anti-inflammatory properties by upregulating the mitochondrial respiration of macrophages in a normal diet-fed mouse model [ 27 ], yet the detailed cellular mechanisms and effects of RBO on obesity-induced chronic inflammation are unclear. Therefore, in the current study, we evaluated the effects of RBO on inflammatory markers in epididymal white adipose tissue (eWAT) in vivo and further examined its influence on polarization of bone marrow-derived macrophages (BMDMs) ex vivo, which are involved in systemic immune responses using a high-fat diet mouse model.…”